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The final authenticated version is available online at: </w:t></w:r><w:r w:rsidR="00674529"><w:fldChar w:fldCharType="begin"/></w:r><w:r w:rsidR="00674529" w:rsidRPr="0088649E"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:instrText xml:space="preserve"> HYPERLINK "https://doi.org/10.1016/j.bbr.2018.01.006" </w:instrText></w:r><w:r w:rsidR="00674529"><w:fldChar w:fldCharType="separate"/></w:r><w:r w:rsidR="00EF75D4" w:rsidRPr="005C55E2"><w:rPr><w:rStyle w:val="Hipervnculo"/><w:sz w:val="28"/><w:szCs w:val="28"/><w:lang w:val="en-US"/></w:rPr><w:t>https://doi.org/10.1016/j.bbr.2018.01.006</w:t></w:r><w:r w:rsidR="00674529"><w:rPr><w:rStyle w:val="Hipervnculo"/><w:sz w:val="28"/><w:szCs w:val="28"/><w:lang w:val="en-US"/></w:rPr><w:fldChar w:fldCharType="end"/></w:r><w:r w:rsidR="00EF75D4"><w:rPr><w:sz w:val="28"/><w:szCs w:val="28"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="0014435A"><w:rPr><w:sz w:val="28"/><w:szCs w:val="28"/><w:lang w:val="en-US"/></w:rPr><w:t>"</w:t></w:r></w:p><w:p w14:paraId="36B398B6" w14:textId="77777777" w:rsidR="0014435A" w:rsidRDefault="0014435A" w:rsidP="0014435A"><w:pPr><w:rPr><w:rFonts w:eastAsiaTheme="majorEastAsia" w:cstheme="majorBidi"/><w:sz w:val="22"/><w:szCs w:val="32"/><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:br w:type="page"/></w:r></w:p><w:p w14:paraId="22F645E7" w14:textId="77777777" w:rsidR="009F4FCB" w:rsidRDefault="008142E0" w:rsidP="008142E0"><w:pPr><w:pStyle w:val="Ttulo1"/><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="008142E0"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:lastRenderedPageBreak/><w:t>Differential requirement of de novo Arc protein synthesis in the insular</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008142E0"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>cortex and the amygdala for safe and aversive taste long-term memory</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008142E0"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>formation</w:t></w:r></w:p><w:p w14:paraId="5CE462D8" w14:textId="77777777" w:rsidR="008142E0" w:rsidRDefault="008142E0" w:rsidP="00AB3146"><w:pPr><w:spacing w:after="120"/><w:jc w:val="center"/><w:rPr><w:vertAlign w:val="superscript"/></w:rPr></w:pPr><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="008142E0"><w:t>Kioko</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="008142E0"><w:t xml:space="preserve"> Guzmán-Ramos</w:t></w:r><w:r w:rsidRPr="008142E0"><w:rPr><w:vertAlign w:val="superscript"/></w:rPr><w:t>1</w:t></w:r><w:r w:rsidRPr="008142E0"><w:t xml:space="preserve">, </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="008142E0"><w:t>Archana</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="008142E0"><w:t xml:space="preserve"> Venkataraman</w:t></w:r><w:r><w:rPr><w:vertAlign w:val="superscript"/></w:rPr><w:t>2</w:t></w:r><w:r w:rsidRPr="008142E0"><w:t>, Jean-Pascal Morin</w:t></w:r><w:r w:rsidRPr="008142E0"><w:rPr><w:vertAlign w:val="superscript"/></w:rPr><w:t>4</w:t></w:r><w:r w:rsidRPr="008142E0"><w:t>, Daniel Osorio-G</w:t></w:r><w:r w:rsidRPr="008142E0"><w:rPr><w:rFonts w:ascii="Arial" w:hAnsi="Arial" w:cs="Arial"/></w:rPr><w:t>ó</w:t></w:r><w:r w:rsidRPr="008142E0"><w:t>mez</w:t></w:r><w:r><w:rPr><w:vertAlign w:val="superscript"/></w:rPr><w:t>1,3</w:t></w:r><w:r w:rsidRPr="008142E0"><w:t>,</w:t></w:r><w:r><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008142E0"><w:t>Federico Bermúdez-Rattoni</w:t></w:r><w:r><w:rPr><w:vertAlign w:val="superscript"/></w:rPr><w:t>3</w:t></w:r></w:p><w:p w14:paraId="40B0CD96" w14:textId="77777777" w:rsidR="0089482D" w:rsidRPr="00AB3146" w:rsidRDefault="00E540BE" w:rsidP="00E540BE"><w:pPr><w:jc w:val="center"/><w:rPr><w:sz w:val="17"/><w:szCs w:val="17"/></w:rPr></w:pPr><w:r w:rsidRPr="00AB3146"><w:rPr><w:sz w:val="17"/><w:szCs w:val="17"/><w:vertAlign w:val="superscript"/></w:rPr><w:t xml:space="preserve">1 </w:t></w:r><w:r w:rsidR="0089482D" w:rsidRPr="00AB3146"><w:rPr><w:sz w:val="17"/><w:szCs w:val="17"/></w:rPr><w:t xml:space="preserve">Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Unidad Lerma, Av. De las Garzas No. 10, Col. El Panteón, Lerma de Villada, Estado de México, C.P. 52005, México. </w:t></w:r><w:r w:rsidR="0089482D" w:rsidRPr="00AB3146"><w:rPr><w:sz w:val="17"/><w:szCs w:val="17"/><w:vertAlign w:val="superscript"/><w:lang w:val="en-US"/></w:rPr><w:t>2</w:t></w:r><w:r w:rsidR="0089482D" w:rsidRPr="00AB3146"><w:rPr><w:sz w:val="17"/><w:szCs w:val="17"/><w:lang w:val="en-US"/></w:rPr><w:t>Department of Biology, Texas A&amp;M University, College Station, TX, 77845, United States</w:t></w:r><w:r w:rsidRPr="00AB3146"><w:rPr><w:sz w:val="17"/><w:szCs w:val="17"/><w:lang w:val="en-US"/></w:rPr><w:t>.</w:t></w:r><w:r w:rsidR="0089482D" w:rsidRPr="00AB3146"><w:rPr><w:sz w:val="17"/><w:szCs w:val="17"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00AB3146"><w:rPr><w:sz w:val="17"/><w:szCs w:val="17"/><w:vertAlign w:val="superscript"/></w:rPr><w:t>3</w:t></w:r><w:r w:rsidR="0089482D" w:rsidRPr="00AB3146"><w:rPr><w:sz w:val="17"/><w:szCs w:val="17"/></w:rPr><w:t xml:space="preserve">Departamento de Neurociencias, Instituto de Fisiología Celular, </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidR="0089482D" w:rsidRPr="00AB3146"><w:rPr><w:sz w:val="17"/><w:szCs w:val="17"/></w:rPr><w:t>Mexico</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00AB3146"><w:rPr><w:sz w:val="17"/><w:szCs w:val="17"/></w:rPr><w:t xml:space="preserve">. </w:t></w:r><w:r w:rsidRPr="00AB3146"><w:rPr><w:sz w:val="17"/><w:szCs w:val="17"/><w:vertAlign w:val="superscript"/></w:rPr><w:t>4</w:t></w:r><w:r w:rsidR="0089482D" w:rsidRPr="00AB3146"><w:rPr><w:sz w:val="17"/><w:szCs w:val="17"/></w:rPr><w:t xml:space="preserve">Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Apartado Postal 70-253, 04510 México D.F., </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidR="0089482D" w:rsidRPr="00AB3146"><w:rPr><w:sz w:val="17"/><w:szCs w:val="17"/></w:rPr><w:t>Mexico</w:t></w:r><w:proofErr w:type="spellEnd"/></w:p><w:p w14:paraId="59CBDA84" w14:textId="77777777" w:rsidR="003E4C83" w:rsidRDefault="003E4C83" w:rsidP="00E540BE"><w:pPr><w:jc w:val="center"/><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/></w:rPr></w:pPr></w:p><w:p w14:paraId="7C8AF0C9" w14:textId="77777777" w:rsidR="003E4C83" w:rsidRDefault="003E4C83" w:rsidP="003E4C83"><w:pPr><w:pStyle w:val="Ttulo2"/><w:rPr><w:b w:val="0"/><w:bCs/><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="003E4C83"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Keywords:</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="007876E6"><w:rPr><w:b w:val="0"/><w:bCs/><w:lang w:val="en-US"/></w:rPr><w:t>Conditioned taste aversion</w:t></w:r><w:r w:rsidRPr="00B03188"><w:rPr><w:b w:val="0"/><w:bCs/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">; </w:t></w:r><w:r w:rsidRPr="007876E6"><w:rPr><w:b w:val="0"/><w:bCs/><w:lang w:val="en-US"/></w:rPr><w:t>Safe taste memory</w:t></w:r><w:r w:rsidRPr="00B03188"><w:rPr><w:b w:val="0"/><w:bCs/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">; </w:t></w:r><w:r w:rsidRPr="007876E6"><w:rPr><w:b w:val="0"/><w:bCs/><w:lang w:val="en-US"/></w:rPr><w:t>Insular cortex</w:t></w:r><w:r w:rsidRPr="00B03188"><w:rPr><w:b w:val="0"/><w:bCs/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">; </w:t></w:r><w:r w:rsidRPr="007876E6"><w:rPr><w:b w:val="0"/><w:bCs/><w:lang w:val="en-US"/></w:rPr><w:t>Amygdala</w:t></w:r><w:r w:rsidRPr="00B03188"><w:rPr><w:b w:val="0"/><w:bCs/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">; </w:t></w:r><w:r w:rsidRPr="007876E6"><w:rPr><w:b w:val="0"/><w:bCs/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">Activity regulated </w:t></w:r><w:proofErr w:type="gramStart"/><w:r w:rsidRPr="007876E6"><w:rPr><w:b w:val="0"/><w:bCs/><w:lang w:val="en-US"/></w:rPr><w:t>cytoskeletal-associated</w:t></w:r><w:proofErr w:type="gramEnd"/><w:r w:rsidRPr="00B03188"><w:rPr><w:b w:val="0"/><w:bCs/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">; </w:t></w:r><w:r w:rsidRPr="007876E6"><w:rPr><w:b w:val="0"/><w:bCs/><w:lang w:val="en-US"/></w:rPr><w:t>protein</w:t></w:r><w:r w:rsidR="00B03188"><w:rPr><w:b w:val="0"/><w:bCs/><w:lang w:val="en-US"/></w:rPr><w:t>.</w:t></w:r></w:p><w:p w14:paraId="7944525E" w14:textId="77777777" w:rsidR="00B03188" w:rsidRPr="00B03188" w:rsidRDefault="00B03188" w:rsidP="00356D7B"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr></w:p><w:p w14:paraId="4D18CA06" w14:textId="77777777" w:rsidR="00B03188" w:rsidRPr="0088649E" w:rsidRDefault="00B03188" w:rsidP="00B03188"><w:pPr><w:pStyle w:val="Ttulo2"/><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="0088649E"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Abstract</w:t></w:r></w:p><w:p w14:paraId="4B0B14FB" w14:textId="77777777" w:rsidR="00356D7B" w:rsidRDefault="00356D7B" w:rsidP="00356D7B"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00356D7B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Several immediate early genes products are known to be involved in the facilitation of structural and functional</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00356D7B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>modifications at distinct synapses activated through experience. The IEG-encoded protein Arc (activity regulated</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00356D7B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>cytoskeletal-associated protein) has been widely implicated in long-term memory formation and stabilization. In</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00356D7B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>this study, we sought to evaluate a possible role for de novo Arc protein synthesis in the insular cortex (IC) and in</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00356D7B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>the amygdala (AMY) during long-term taste memory formation. We found that acute inhibition of Arc protein</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00356D7B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>synthesis through the infusion of antisense oligonucleotides administered in the IC before a novel taste presentation,</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00356D7B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>affected consolidation of a safe taste memory trace (ST) but spared consolidation of conditioned taste</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00356D7B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>aversion (CTA). Conversely, blocking Arc synthesis within the AMY impaired CTA consolidation but had no</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00356D7B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>effect on ST long-term memory formation. Our results suggest that Arc-dependent plasticity during taste learning</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00356D7B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>is required within distinct structures of the medial temporal lobe, depending on the emotional valence of the</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00356D7B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>memory trace.</w:t></w:r></w:p><w:p w14:paraId="0330C1FF" w14:textId="77777777" w:rsidR="00A43EA5" w:rsidRDefault="00A43EA5" w:rsidP="00A43EA5"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr></w:p><w:p w14:paraId="008EFAD4" w14:textId="77777777" w:rsidR="00A43EA5" w:rsidRDefault="00A43EA5" w:rsidP="00A43EA5"><w:pPr><w:pStyle w:val="Ttulo2"/><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Introduction</w:t></w:r></w:p><w:p w14:paraId="08394A6C" w14:textId="77777777" w:rsidR="00A43EA5" w:rsidRDefault="00A43EA5" w:rsidP="00E73DC4"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>The nature of the information to be incorporated seems crucial in</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>determining the structural and molecular events that are triggered to</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>consolidate a memory trace. A very useful memory paradigm to study</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>such plastic changes is taste memory, in which either “safe” or “aversive”</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>memory traces will be formed based on the presence or absence of</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>gastric malaise [1]. The conditioned taste aversion (CTA) is expressed</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>as a diminished consumption of the food associated with gastric malaise,</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>whereas if there are no negative outcomes from the food consumption,</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>the animal will keep consuming it, and will be stored as a</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>safe taste memory trace (ST) [1]. Acquisition and consolidation of taste</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>memories are primarily dependent on the activity of the insular cortex</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>(IC) [1] and the establishment of a taste memory trace on the long-term</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>involves de novo translation of plasticity-related proteins in this structure</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>such as expression of the transcription factor c-</w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>fos</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> [2], the synthesis</w:t></w:r><w:r w:rsidR="008801B1"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>of the scaffolding protein PSD-95 [3] and the neurotrophic factor BDNF</w:t></w:r><w:r w:rsidR="008801B1"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00A43EA5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>[4].</w:t></w:r></w:p><w:p w14:paraId="18E8CC93" w14:textId="77777777" w:rsidR="00E73DC4" w:rsidRPr="00E73DC4" w:rsidRDefault="00E73DC4" w:rsidP="00E73DC4"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Another important structure for taste memory formation is the</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>amygdala (AMY) both central and basolateral nuclei. For instance, it</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>has been shown that the exposure to a novel saccharin solution induces</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>c-</w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>fos</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> synthesis in the central amygdala (</w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>CeA</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>) [5,6] and gastric malaise</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">induction is related to both the </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>CeA</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> and the basolateral amygdala (BLA)</w:t></w:r></w:p><w:p w14:paraId="35FCE4B9" w14:textId="77777777" w:rsidR="00E73DC4" w:rsidRPr="00E73DC4" w:rsidRDefault="00E73DC4" w:rsidP="00E73DC4"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>activity [6]. Interestingly, the pairing of a novel taste with gastric</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>malaise induced a strong increase in c-</w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>fos</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>-immunoreactive neurons in</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">both </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>CeA</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> and BLA compared to gastric malaise induction after drinking</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>a familiar taste [7].</w:t></w:r></w:p><w:p w14:paraId="41DF5784" w14:textId="77777777" w:rsidR="006C5EBA" w:rsidRDefault="00E73DC4" w:rsidP="006C5EBA"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Previously, we have shown that taste-induced synthesis of activity</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>regulated</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>cytoskeletal associated protein (Arc), an immediate early</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>gene with a pivotal role in synaptic plasticity [9,10], is increased in</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>dendritic regions of the IC after familiarization with the taste during ST</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>[11], suggesting a role in this type of learning. In the case of AMY,</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>gustatory and visceral stimuli association induce Arc mRNA expression</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">that converge on the same </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>amygdalar</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> neurons during the establishment</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>of taste aversion [8]; however, no study has addressed directly the requirement</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E73DC4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>for Arc translation in the consolidation of both “safe” and</w:t></w:r><w:r w:rsidR="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="006C5EBA" w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>“aversive” taste memory traces within the IC and the AMY. We propose</w:t></w:r><w:r w:rsidR="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="006C5EBA" w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>that Arc protein in these structures is required differentially in the long</w:t></w:r><w:r w:rsidR="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>-</w:t></w:r><w:r w:rsidR="006C5EBA" w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>term</w:t></w:r><w:r w:rsidR="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="006C5EBA" w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>taste memory formation depending on the kind of learning. To</w:t></w:r><w:r w:rsidR="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="006C5EBA" w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>evaluate this, we conducted Arc protein knockdown experiments on the</w:t></w:r><w:r w:rsidR="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="006C5EBA" w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">afore mentioned brain </w:t></w:r><w:r w:rsidR="006C5EBA" w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:lastRenderedPageBreak/><w:t>structures with antisense oligonucleotides (ODN)</w:t></w:r><w:r w:rsidR="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="006C5EBA" w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>during the acquisition of ST or CTA. Our results show that Arc protein</w:t></w:r><w:r w:rsidR="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="006C5EBA" w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>synthesis in the IC is involved in the safe taste long-term memory impeding</w:t></w:r><w:r w:rsidR="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="006C5EBA" w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>the familiarization process; this may suggest that Arc participates</w:t></w:r><w:r w:rsidR="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="006C5EBA" w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>in safe taste storage. Conversely, Arc synthesis within the AMY</w:t></w:r><w:r w:rsidR="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="006C5EBA" w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>appears to be involved only in the CTA stabilization, which shows a</w:t></w:r><w:r w:rsidR="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="006C5EBA" w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>versatile role of Arc depending on the outcome of the food ingestion to</w:t></w:r><w:r w:rsidR="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="006C5EBA" w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>form either safe or aversive memory traces.</w:t></w:r><w:r w:rsidR="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r></w:p><w:p w14:paraId="302D4BDB" w14:textId="77777777" w:rsidR="006C5EBA" w:rsidRPr="006C5EBA" w:rsidRDefault="006C5EBA" w:rsidP="006C5EBA"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Ninety days-old male Wistar rats, weighing 260–280 g, were housed</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>individually in a temperature-controlled environment and maintained</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>on a 12-h light/dark cycle. They had ad libitum access to food and</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>water, except when noted otherwise in the experimental procedures.</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Studies were performed in accordance with the standards of the</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>National Institutes of Health Guide for Care and Use of Laboratory</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">Animals and were approved by the Instituto de </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Fisiología</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Celular</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> and</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>the Institutional Animal Care and Use Committee SAAC from Texas A&amp;</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>M University under AUP 201141.</w:t></w:r></w:p><w:p w14:paraId="54C3CF6C" w14:textId="77777777" w:rsidR="00E73DC4" w:rsidRDefault="006C5EBA" w:rsidP="006C5EBA"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>The ODN for Arc/</w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Arg</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> 3.1 mRNA and a </w:t></w:r><w:proofErr w:type="gramStart"/><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>scrambled oligonucleotides</w:t></w:r><w:proofErr w:type="gramEnd"/><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>sequence (SCR) (Midland Certified Reagent Company, TX, USA) were</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>custom made as following the nucleotides sequence described by</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Guzowski</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> et al. [12]. Guide </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>cannulae</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> were implanted bilaterally into</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>the IC and the AMY in independent groups using standard stereotaxic</w:t></w:r><w:r w:rsidR="002F6F9B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>procedures. The coordinates were determined from bregma (in mm):</w:t></w:r><w:r w:rsidR="002F6F9B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>AP</w:t></w:r><w:r w:rsidR="002F6F9B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>+1.2, L ± 5.5 and DV –4.5 for IC, and AP −2.8 mm; L ± 4.8 mm;</w:t></w:r><w:r w:rsidR="002F6F9B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>DV –6.5</w:t></w:r><w:r w:rsidR="002F6F9B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">mm to aim a point where the infusion would include </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>CeA</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> and</w:t></w:r><w:r w:rsidR="002F6F9B"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">BLA according to </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Paxinos</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="006C5EBA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> and Watson [13].</w:t></w:r></w:p><w:p w14:paraId="76F94B48" w14:textId="77777777" w:rsidR="00B42393" w:rsidRPr="00B42393" w:rsidRDefault="00FE386F" w:rsidP="00B42393"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00FE386F"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>One week after surgery, behavioral experiments were performed to</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00FE386F"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>assess the functional role of Arc synthesis within the IC and the AMY in</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00FE386F"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>taste memory. Rats were water-restricted for 24 h and a baseline water</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00FE386F"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>consumption was determined by allowing access to tap water for</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00FE386F"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>15 min in the morning (around 10:00 a.m.) and for 15 min in the</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00FE386F"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>afternoon (around 6:00 p.m.). After five days of baseline consumption</w:t></w:r><w:r w:rsidR="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>recording, these animals were then divided into two groups with similar</w:t></w:r><w:r w:rsidR="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">baseline consumption of water: aversive </w:t></w:r><w:r w:rsidR="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">  </w:t></w:r><w:proofErr w:type="gramStart"/><w:r w:rsidR="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">   </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>(</w:t></w:r><w:proofErr w:type="gramEnd"/><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>SAC+</w:t></w:r><w:r w:rsidR="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>LiCl) and safe</w:t></w:r><w:r w:rsidR="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>(SAC</w:t></w:r><w:r w:rsidR="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>+</w:t></w:r><w:r w:rsidR="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">NaCl). Half of the aversive group received injections of </w:t></w:r><w:proofErr w:type="gramStart"/><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>ODN</w:t></w:r><w:proofErr w:type="gramEnd"/><w:r w:rsidR="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">and half received SCR (1 </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>μl</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> (2 nmol)). ODN or SCR were injected one</w:t></w:r><w:r w:rsidR="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>hour prior to the</w:t></w:r><w:r w:rsidR="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>taste exposure using 30-gauge infusion needles that</w:t></w:r><w:r w:rsidR="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>protruded 1.5</w:t></w:r><w:r w:rsidR="00D15BF8"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>mm from the cannula</w:t></w:r><w:r w:rsidR="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>tip; the injection needles remained</w:t></w:r><w:r w:rsidR="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">in the guide </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>cannulae</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> for an additional minute to allow</w:t></w:r><w:r w:rsidR="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>diffusion of</w:t></w:r><w:r w:rsidR="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>fluid into the tissue. Rats in the aversive group were provided with</w:t></w:r><w:r w:rsidR="00D15BF8"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>0.1% (w/v) saccharin solution for 15 min. After 30 min, 7.5 ml/kg of</w:t></w:r><w:r w:rsidR="00D15BF8"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>LiCl 0.15M was injected intraperitoneally. This procedure results in</w:t></w:r><w:r w:rsidR="00D15BF8"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>acquisition of CTA. For acquisition of safe taste memory, the outlined</w:t></w:r><w:r w:rsidR="00D15BF8"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00B42393" w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>behavioral protocol was followed, except that 0.15M NaCl injections</w:t></w:r></w:p><w:p w14:paraId="54C9FC52" w14:textId="77777777" w:rsidR="00FE386F" w:rsidRDefault="00B42393" w:rsidP="00B42393"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>replaced LiCl. Twenty-four hours after the acquisition of either CTA or</w:t></w:r><w:r w:rsidR="00D15BF8"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>ST, a 0.1% saccharin solution was provided during 15 min to assess</w:t></w:r><w:r w:rsidR="00D15BF8"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00B42393"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>long-term memory.</w:t></w:r></w:p><w:p w14:paraId="63E1B6AB" w14:textId="77777777" w:rsidR="000E698A" w:rsidRPr="000E698A" w:rsidRDefault="000E698A" w:rsidP="000E698A"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>To evaluate the extent of Arc protein knockdown after ODN treatment,</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>three rats were administered with ODN in one hemisphere and</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>SCR on the other one hour before the consumption of a saccharin solution</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>during either ST protocol for the IC analysis or CTA for the AMY.</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>One hour after the corresponding protocol, animals were decapitated</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>and their brains flash-frozen and stored at −80 °C until use. Coronal</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">sections of 20 </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>μm</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> were incubated with Arc primary antibody (1:500 in</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>TBS Affinity purified rabbit anti-activity regulated cytoskeletal-associated</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>protein, Synaptic Systems, Gottingen, Germany) overnight at</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>room temperature. On the following day, slices were incubated with</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>biotinylated goat-antirabbit (1:2000, Vector Laboratories, CA, USA) for</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>2 h. Finally, sections were incubated in ABC amplification kit (Vector</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>laboratories, CA, USA), washed thoroughly and the diaminobenzidine</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>reaction was performed.</w:t></w:r></w:p><w:p w14:paraId="6529B900" w14:textId="77777777" w:rsidR="000E698A" w:rsidRPr="000E698A" w:rsidRDefault="000E698A" w:rsidP="000E698A"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>To perform the Arc synthesis analysis, between 3 and 5 images per</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">hemisphere were obtained with a Nikon </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Diaphot</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> 300 microscope and</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>photomicrographs were digitalized with the help of Nikon’s NEF coder</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>software. For the study of the IC and AMY, images were obtained with a</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">4X or 10X objective and included whole coronal </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>hemisections</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>. All</w:t></w:r></w:p><w:p w14:paraId="0CAB3103" w14:textId="77777777" w:rsidR="000E698A" w:rsidRDefault="000E698A" w:rsidP="00905AF5"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>image processing and analyses were performed using NIH ImageJ</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="000E698A"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>software. Masks generated by the threshold were examined in search</w:t></w:r><w:r w:rsidR="00905AF5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00905AF5" w:rsidRPr="00905AF5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>for putative staining artifacts that may have been included in the calculation</w:t></w:r><w:r w:rsidR="00905AF5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00905AF5" w:rsidRPr="00905AF5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>and on these rare instances, these objects were removed from</w:t></w:r><w:r w:rsidR="00905AF5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00905AF5" w:rsidRPr="00905AF5"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>the analyses.</w:t></w:r></w:p><w:p w14:paraId="1E83E4CF" w14:textId="77777777" w:rsidR="009E5420" w:rsidRDefault="009E5420" w:rsidP="009E5420"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>A Mann-Whitney test indicated that the count of Arc positive cells</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>was higher for SCR-infused tissue than for ODN-infused tissue in both IC</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>and AMY (p</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>0.0495 and p</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>0.0228, respectively). We observed that</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>administration of ODN significantly decreases Arc levels within the IC</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>and the AMY compared to the contralateral SCR infusion (Fig. 1A–E).</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>To confirm that the extension of the Arc synthesis inhibition did not</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>affect beyond the intended brain structures, we analyzed adjacent areas</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>as outlined in Fig. 1A marked as 1 and 2 for the IC and in Fig. 1D</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>marked as 1–4 for the AMY area comprising basolateral and central</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>amygdala. There were no significant differences on the number of</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Arc</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>+</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>cells on the marked areas between the SCR and the ODN groups</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>(Fig. 1C, area 1 p</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">0.8273 and </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:lastRenderedPageBreak/><w:t>area 2 p</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>0.8273; Fig. 1F, area 1</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>p</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>0.8273, area 2 p</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>0.1904, area 3 p</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>0.6625, area 4 p</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>0.5127)</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>indicating that the behavioral effects described after the Arc synthesis</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>blockage are due to the decrease of Arc protein necessary for the</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="009E5420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>memory trace stabilization within the AMY and the IC.</w:t></w:r></w:p><w:p w14:paraId="44ED8CD3" w14:textId="77777777" w:rsidR="000D16E0" w:rsidRDefault="000D16E0" w:rsidP="000D16E0"><w:pPr><w:keepNext/><w:jc w:val="center"/></w:pPr><w:r><w:rPr><w:noProof/><w:lang w:val="en-US"/></w:rPr><w:drawing><wp:inline distT="0" distB="0" distL="0" distR="0" wp14:anchorId="67DF9B47" wp14:editId="0854ED01"><wp:extent cx="5826868" cy="2919037"/><wp:effectExtent l="0" t="0" r="2540" b="0"/><wp:docPr id="1" name="Imagen 1" descr="Imagen que contiene reloj&#xA;&#xA;Descripción generada automáticamente"/><wp:cNvGraphicFramePr><a:graphicFrameLocks xmlns:a="http://schemas.openxmlformats.org/drawingml/2006/main" noChangeAspect="1"/></wp:cNvGraphicFramePr><a:graphic xmlns:a="http://schemas.openxmlformats.org/drawingml/2006/main"><a:graphicData uri="http://schemas.openxmlformats.org/drawingml/2006/picture"><pic:pic xmlns:pic="http://schemas.openxmlformats.org/drawingml/2006/picture"><pic:nvPicPr><pic:cNvPr id="1" name="Differential requiremen_f1.jpg"/><pic:cNvPicPr/></pic:nvPicPr><pic:blipFill><a:blip r:embed="rId6"><a:extLst><a:ext uri="{28A0092B-C50C-407E-A947-70E740481C1C}"><a14:useLocalDpi xmlns:a14="http://schemas.microsoft.com/office/drawing/2010/main" val="0"/></a:ext></a:extLst></a:blip><a:stretch><a:fillRect/></a:stretch></pic:blipFill><pic:spPr><a:xfrm><a:off x="0" y="0"/><a:ext cx="5843998" cy="2927619"/></a:xfrm><a:prstGeom prst="rect"><a:avLst/></a:prstGeom></pic:spPr></pic:pic></a:graphicData></a:graphic></wp:inline></w:drawing></w:r></w:p><w:p w14:paraId="68405A42" w14:textId="05E623D8" w:rsidR="000D16E0" w:rsidRPr="00E4586E" w:rsidRDefault="000D16E0" w:rsidP="000D16E0"><w:pPr><w:pStyle w:val="Descripcin"/><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00E4586E"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">Fig.  </w:t></w:r><w:r w:rsidRPr="00E4586E"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/></w:rPr><w:fldChar w:fldCharType="begin"/></w:r><w:r w:rsidRPr="00E4586E"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:instrText xml:space="preserve"> SEQ Fig._ \* ARABIC </w:instrText></w:r><w:r w:rsidRPr="00E4586E"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/></w:rPr><w:fldChar w:fldCharType="separate"/></w:r><w:r w:rsidR="0088649E"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:noProof/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t>1</w:t></w:r><w:r w:rsidRPr="00E4586E"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/></w:rPr><w:fldChar w:fldCharType="end"/></w:r><w:r w:rsidR="00A84377" w:rsidRPr="00E4586E"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">. </w:t></w:r><w:r w:rsidRPr="00E4586E"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">(A) Representative images from IC sections 10X and 4X reconstruction </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00E4586E"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t>immunostained</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00E4586E"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> for Arc protein showing the effect of scrambled oligodeoxynucleotide (SCR) injection and contralateral hemisphere administration of Arc antisense oligodeoxynucleotide (ODN). (B) Quantification of Arc + cells ± S.E.M in the IC 1 h after the safe taste memory protocol is substantially reduced in the ODN group as compared with the SCR group (*p=0.0495). (C) Quantification of Arc + cells ± S.E.M on the outlined areas adjacent to the IC: area 1 somatosensory cortex and area 2 piriform cortex showing no significant difference. (D) Representative images from AMY sections 10X and 4X reconstruction </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00E4586E"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t>immunostained</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00E4586E"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> for Arc protein on SCR and ODN groups. (E) Arc + cells ± S.E.M. quantification on the region of the amygdala where the injection was performed (SCR vs. ODN group #p=0.0228). (F) Quantification of </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00E4586E"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t>Arc+cells</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00E4586E"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> ± S.E.M on the outlined areas adjacent to the basolateral and central amygdala: area 1 </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00E4586E"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t>amygdalostriatal</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00E4586E"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> transition area and ventral caudate, area 2 dorsal </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00E4586E"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t>endopiriform</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00E4586E"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> nucleus, area 3 </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00E4586E"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t>basomedial</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00E4586E"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> amygdaloid nucleus, area 4 bed nucleus of the stria terminalis; showing no significant decrease of </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00E4586E"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t>Arc+cells</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00E4586E"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> on the ODN group.</w:t></w:r></w:p><w:p w14:paraId="07D38D7E" w14:textId="77777777" w:rsidR="005379AF" w:rsidRDefault="00D022C2" w:rsidP="00D022C2"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>To verify the site of injection, histological analysis of the brains was</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">performed at the end of the experimental period using </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>cresyl</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> violet</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>staining of 40-μm thick coronal brain slices for microscopic observation.</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">Rats with an incorrect </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>cannulae</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> placement were removed from the</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>experiment. Final number of animals per groups is specified in Fig. 2</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>legend; cannula placement is shown in Fig. 3.</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r></w:p><w:p w14:paraId="59E7C362" w14:textId="77777777" w:rsidR="00D022C2" w:rsidRPr="00D022C2" w:rsidRDefault="00D022C2" w:rsidP="00D022C2"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>The behavioral effect of ODN and SCR administrations for each</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>behavioral paradigm was analyzed using one-way ANOVA assessing the</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>effect of the ODN infusion on either IC or AMY on the long-term</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>memory formation. Bonferroni post hoc analyses were conducted, and</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>statistical significance was determined if p-value</w:t></w:r><w:r w:rsidR="005379AF"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>&lt;</w:t></w:r><w:r w:rsidR="005379AF"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>0.05 in all cases.</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Values are presented as mean ± S.E.M. All statistical analyses were</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">performed with </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>StatView</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> (Abacus Concepts Inc.). Milliliters consumed</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>during the first saccharin presentation were analyzed to rule out a behavioral</w:t></w:r><w:r w:rsidR="005379AF"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>effect of the ODN or SCR injections on the day of the task</w:t></w:r><w:r w:rsidR="005379AF"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>acquisition (Fig. 2A and C). One-way ANOVA showed that there were</w:t></w:r><w:r w:rsidR="005379AF"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>no significant statistical differences in the mean consumption of the</w:t></w:r><w:r w:rsidR="005379AF"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>novel saccharin during the ST task (F3,23</w:t></w:r><w:r w:rsidR="005379AF"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r w:rsidR="005379AF"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>2.423, p</w:t></w:r><w:r w:rsidR="005379AF"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r w:rsidR="005379AF"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>0.0917), nor</w:t></w:r><w:r w:rsidR="007C20EC"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>the CTA task (F3,22</w:t></w:r><w:r w:rsidR="007C20EC"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r w:rsidR="007C20EC"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>1.081, p</w:t></w:r><w:r w:rsidR="007C20EC"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r w:rsidR="007C20EC"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>0.3776). The effect of the ODN or</w:t></w:r><w:r w:rsidR="007C20EC"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>SCR injection on the second presentation of saccharin was expressed as</w:t></w:r></w:p><w:p w14:paraId="2B3F71AD" w14:textId="77777777" w:rsidR="008368D6" w:rsidRPr="008368D6" w:rsidRDefault="00D022C2" w:rsidP="008368D6"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">the percentage of the first saccharin </w:t></w:r><w:proofErr w:type="gramStart"/><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>consumption;</w:t></w:r><w:proofErr w:type="gramEnd"/><w:r w:rsidRPr="00D022C2"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> i.e. SAC</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>DAY2</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>[(saccharin mL day 2</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>×</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>100)/saccharin mL day 1]. As shown</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>in the Fig. 2B regarding the ST, there was a significant effect of ODN</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>infusion before a novel taste presentation that was not paired with</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>malaise (F3,23</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>7.035, p</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>0.0016), Bonferroni/Dunn post hoc revealed</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>that saccharin consumption on day 2 was significantly different</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>in the ODN IC group than in the SCR IC group (p</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>0.0022); no statistical</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>differences were observed on the AMY groups, suggesting a</w:t></w:r><w:r w:rsidR="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="008368D6" w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>specific role of Arc translation in the IC, but not in the AMY for safe</w:t></w:r></w:p><w:p w14:paraId="3BF8C2FA" w14:textId="77777777" w:rsidR="008368D6" w:rsidRPr="008368D6" w:rsidRDefault="008368D6" w:rsidP="008368D6"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>taste long-term memory formation.</w:t></w:r></w:p><w:p w14:paraId="515CD573" w14:textId="77777777" w:rsidR="008368D6" w:rsidRPr="008368D6" w:rsidRDefault="008368D6" w:rsidP="008368D6"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>For CTA, one-way ANOVA analysis shows a significant difference on</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>the second day saccharin consumption between groups (F3,22</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>4.289,</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>p</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>=</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>0.0158), and post-hoc analysis revealed that only the AMY ODN</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">group showed hindered </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:lastRenderedPageBreak/><w:t>CTA (p=0.0028); indicating that blockade of</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Arc synthesis affects only the stabilization of the aversive memory trace</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>within the AMY, but not within the IC (Fig. 2D).</w:t></w:r></w:p><w:p w14:paraId="71757471" w14:textId="77777777" w:rsidR="00D022C2" w:rsidRDefault="008368D6" w:rsidP="008368D6"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>In the last few years, the role of Arc in memory consolidation has</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>been established for distinct types of memory [12,20]. Here we provide</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">the first evidence for a requirement of cortical and </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>amygdalar</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> de novo</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Arc protein synthesis as part of the molecular mechanisms involved in</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">taste long-term memory formation. We observed that infusion of </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Arcantisense</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>ODN in the IC 1 h before the intake of a novel taste affected</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>long-term safe taste memory formation but spared CTA consolidation.</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>On the other hand, the same treatment performed in the AMY, alters</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="008368D6"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>CTA memory formation, but leaves safe memory intact.</w:t></w:r></w:p><w:p w14:paraId="420100D2" w14:textId="77777777" w:rsidR="00AE2420" w:rsidRPr="00AE2420" w:rsidRDefault="00AE2420" w:rsidP="00AE2420"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>The differential involvement of Arc in the AMY and the IC goes in</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">accordance with an earlier study that used the </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>catFISH</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> technique which</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>showed that neurons of the AMY, but not the IC integrated the information</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>related to the taste stimulus and the gastric malaise [8].</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Furthermore, another group found that conditioned odor preference</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>produced convergence of odor and taste information onto BLA but not</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>IC neurons [14]. This absence of evidence for stimuli integration in the</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>IC is in line with the present study that observed no effect of Arc protein</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>knockdown on CTA consolidation. It is important to mention however</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>that a massive amount of evidence supports a role of the IC in aversive</w:t></w:r></w:p><w:p w14:paraId="3B89562D" w14:textId="77777777" w:rsidR="00AE2420" w:rsidRDefault="00AE2420" w:rsidP="00AE2420"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>taste memory such as the one that occurs after CTA. For instance, lesions</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>of specific regions within the IC are known to impair CTA learning</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>[15]. A remapping of neural activity has also been shown to occur</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>during a taste’s shifts in hedonic value, such as those that occur during</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>CTA and CTA extinction [16]. Also, protein synthesis inhibition in the</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00AE2420"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>IC has long been known to impair long-term memory of CTA [17].</w:t></w:r></w:p><w:p w14:paraId="1EBBC6AE" w14:textId="77777777" w:rsidR="00D3491C" w:rsidRDefault="00D3491C" w:rsidP="00D3491C"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">Furthermore, </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Erk</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> and mTOR-dependent de novo translation of PSD-95</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>in the gustatory part of the IC has been shown to be essential for</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>aversive taste memory consolidation [3,18]. All in all, these data suggest</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>that aversive associative memory processes do take place in the IC</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>that allow CTA formation, although the present results suggest that</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>these operate through Arc-independent mechanism. However, participation</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>of Arc in the IC for CTA consolidation during time points beyond</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>the one analyzed in the current study cannot be ruled out.</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r></w:p><w:p w14:paraId="24C1BBE2" w14:textId="77777777" w:rsidR="00D3491C" w:rsidRPr="00D3491C" w:rsidRDefault="00D3491C" w:rsidP="00D3491C"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Our observation of a requirement for de novo Arc protein synthesis</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>in the AMY for CTA long-term memory formation agrees with previous</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>reports showing that Arc translation in this region is essential for fear</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>conditioning. For instance, knockdown of Arc within the BLA affected</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>long-term memory of an auditory fear conditioning, leaving short-term</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>memory intact [19] and synthesis of Arc in the BLA is involved in</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>persistence of a contextual fear conditioning [20]. Furthermore, genetically</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>blocking the function of a transcription factor involved in Arc</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>expression such as CREB in the BLA has been shown to impair CTA</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>memory [21]. Also, metabotropic glutamate receptors, whose activation</w:t></w:r></w:p><w:p w14:paraId="37518932" w14:textId="77777777" w:rsidR="00D3491C" w:rsidRDefault="00D3491C" w:rsidP="00D3491C"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>is involved in Arc translation [22], are also known to be involved in</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>the AMY for CTA memory formation [23]. Together, these findings</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>suggest that Arc-dependent synaptic plasticity mechanisms in the AMY</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>are essential for long-term memory of aversive associative memory</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>traces.</w:t></w:r></w:p><w:p w14:paraId="4E091091" w14:textId="77777777" w:rsidR="00D3491C" w:rsidRDefault="00D3491C" w:rsidP="00EB5EFA"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Our data seem to agree with a model of gustatory memory consolidation</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>in which Arc-dependent plasticity in the IC, is essential for</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>familiarity processing in the long-term. In a previous work [11], we</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>showed that Arc protein accumulation in the IC positively correlated</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>with taste familiarity. Similarly, a more recent study found that both</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>water and familiar (i.e. non neophobic) saccharin produced higher Arc</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>transcript levels in the gustatory cortex than when rats were exposed to</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>novel saccharin, showing that taste novelty actually down-regulates Arc</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>mRNA expression produced by fluid consumption [24]. Along with our</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>current results describing a role for Arc in the IC for safe, but not</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>aversive, taste memory consolidation, these studies bring up the intriguing</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>possibility that Arc protein synthesis and requirement in the IC</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>may correlate with the appetitive character of the presented taste stimulus</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>rather than familiarity per se, with neophobic taste inducing only</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>weak Arc synthesis while a familiar safe taste induces peak levels.</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Notably, some studies have shown that IC activity is involved in reward</w:t></w:r><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">signaling that is not necessarily linked to the gustatory modality. </w:t></w:r><w:proofErr w:type="gramStart"/><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Indeed</w:t></w:r><w:proofErr w:type="gramEnd"/><w:r><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00D3491C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>electrical stimulation of the IC has rewarding effects under certain</w:t></w:r><w:r w:rsidR="00EB5EFA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00EB5EFA" w:rsidRPr="00EB5EFA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>conditions since it has been shown to promote conditioned place preference</w:t></w:r><w:r w:rsidR="00EB5EFA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00EB5EFA" w:rsidRPr="00EB5EFA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>[25]. Studies evaluating Arc protein synthesis pattern and requirement</w:t></w:r><w:r w:rsidR="00EB5EFA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00EB5EFA" w:rsidRPr="00EB5EFA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>using taste stimuli of varying hedonic properties could help</w:t></w:r><w:r w:rsidR="00EB5EFA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidR="00EB5EFA" w:rsidRPr="00EB5EFA"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>clarify this issue.</w:t></w:r></w:p><w:p w14:paraId="4CCD5681" w14:textId="77777777" w:rsidR="00411CC7" w:rsidRDefault="00411CC7" w:rsidP="00EB5EFA"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr></w:p><w:p w14:paraId="7C7C65CE" w14:textId="77777777" w:rsidR="00411CC7" w:rsidRDefault="00411CC7" w:rsidP="00EB5EFA"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr></w:p><w:p w14:paraId="4B5A92F6" w14:textId="77777777" w:rsidR="00411CC7" w:rsidRDefault="00411CC7" w:rsidP="009B44B4"><w:pPr><w:keepNext/><w:jc w:val="center"/></w:pPr><w:r><w:rPr><w:noProof/><w:lang w:val="en-US"/></w:rPr><w:lastRenderedPageBreak/><w:drawing><wp:inline distT="0" distB="0" distL="0" distR="0" wp14:anchorId="3D14FCA8" wp14:editId="692D82D5"><wp:extent cx="5739319" cy="2390157"/><wp:effectExtent l="0" t="0" r="0" b="0"/><wp:docPr id="2" name="Imagen 2" descr="Captura de pantalla de un celular&#xA;&#xA;Descripción generada automáticamente"/><wp:cNvGraphicFramePr><a:graphicFrameLocks xmlns:a="http://schemas.openxmlformats.org/drawingml/2006/main" noChangeAspect="1"/></wp:cNvGraphicFramePr><a:graphic xmlns:a="http://schemas.openxmlformats.org/drawingml/2006/main"><a:graphicData uri="http://schemas.openxmlformats.org/drawingml/2006/picture"><pic:pic xmlns:pic="http://schemas.openxmlformats.org/drawingml/2006/picture"><pic:nvPicPr><pic:cNvPr id="2" name="F2.jpg"/><pic:cNvPicPr/></pic:nvPicPr><pic:blipFill><a:blip r:embed="rId7"><a:extLst><a:ext uri="{28A0092B-C50C-407E-A947-70E740481C1C}"><a14:useLocalDpi xmlns:a14="http://schemas.microsoft.com/office/drawing/2010/main" val="0"/></a:ext></a:extLst></a:blip><a:stretch><a:fillRect/></a:stretch></pic:blipFill><pic:spPr><a:xfrm><a:off x="0" y="0"/><a:ext cx="5751362" cy="2395173"/></a:xfrm><a:prstGeom prst="rect"><a:avLst/></a:prstGeom></pic:spPr></pic:pic></a:graphicData></a:graphic></wp:inline></w:drawing></w:r></w:p><w:p w14:paraId="6CC4BC69" w14:textId="651EB6B4" w:rsidR="00411CC7" w:rsidRPr="009B44B4" w:rsidRDefault="00411CC7" w:rsidP="00411CC7"><w:pPr><w:pStyle w:val="Descripcin"/><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/></w:rPr></w:pPr><w:r w:rsidRPr="009B44B4"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">Fig.  </w:t></w:r><w:r w:rsidRPr="009B44B4"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/></w:rPr><w:fldChar w:fldCharType="begin"/></w:r><w:r w:rsidRPr="009B44B4"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:instrText xml:space="preserve"> SEQ Fig._ \* ARABIC </w:instrText></w:r><w:r w:rsidRPr="009B44B4"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/></w:rPr><w:fldChar w:fldCharType="separate"/></w:r><w:r w:rsidR="0088649E"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:noProof/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t>2</w:t></w:r><w:r w:rsidRPr="009B44B4"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/></w:rPr><w:fldChar w:fldCharType="end"/></w:r><w:r w:rsidRPr="009B44B4"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t>.</w:t></w:r><w:r w:rsidRPr="009B44B4"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> (A) Saccharin consumption (mL) on Day 1 during ST acquisition phase. (B) Effect of Arc ODN infusions on the formation of long-term safe taste memory in the IC (SCR n=7, ODN n=6) and in the AMY (SCR n=6, ODN n=8). Saccharin consumption of day 2 is represented as % of consumption on the previous day. (C) Saccharin consumption (mL) on Day 1 during CTA acquisition phase. (D) Effect of Arc ODN infusions on the formation long-term aversive memory in the IC (SCR n=7, ODN n=5) and the AMY (SCR n=6, ODN n=7). </w:t></w:r><w:r w:rsidRPr="009B44B4"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/></w:rPr><w:t>*p=0.0022, #p=0.0028.</w:t></w:r></w:p><w:p w14:paraId="527CE834" w14:textId="77777777" w:rsidR="00854A14" w:rsidRDefault="00854A14" w:rsidP="009B44B4"><w:pPr><w:keepNext/><w:jc w:val="center"/></w:pPr><w:r><w:rPr><w:noProof/><w:lang w:val="en-US"/></w:rPr><w:drawing><wp:inline distT="0" distB="0" distL="0" distR="0" wp14:anchorId="1201225D" wp14:editId="508FFC5C"><wp:extent cx="5797685" cy="2877163"/><wp:effectExtent l="0" t="0" r="0" b="0"/><wp:docPr id="3" name="Imagen 3" descr="Imagen que contiene dibujo&#xA;&#xA;Descripción generada automáticamente"/><wp:cNvGraphicFramePr><a:graphicFrameLocks xmlns:a="http://schemas.openxmlformats.org/drawingml/2006/main" noChangeAspect="1"/></wp:cNvGraphicFramePr><a:graphic xmlns:a="http://schemas.openxmlformats.org/drawingml/2006/main"><a:graphicData uri="http://schemas.openxmlformats.org/drawingml/2006/picture"><pic:pic xmlns:pic="http://schemas.openxmlformats.org/drawingml/2006/picture"><pic:nvPicPr><pic:cNvPr id="3" name="F3.jpg"/><pic:cNvPicPr/></pic:nvPicPr><pic:blipFill><a:blip r:embed="rId8"><a:extLst><a:ext uri="{28A0092B-C50C-407E-A947-70E740481C1C}"><a14:useLocalDpi xmlns:a14="http://schemas.microsoft.com/office/drawing/2010/main" val="0"/></a:ext></a:extLst></a:blip><a:stretch><a:fillRect/></a:stretch></pic:blipFill><pic:spPr><a:xfrm><a:off x="0" y="0"/><a:ext cx="5827305" cy="2891862"/></a:xfrm><a:prstGeom prst="rect"><a:avLst/></a:prstGeom></pic:spPr></pic:pic></a:graphicData></a:graphic></wp:inline></w:drawing></w:r></w:p><w:p w14:paraId="1CE4E7A3" w14:textId="6DF2EFDF" w:rsidR="00854A14" w:rsidRPr="009B44B4" w:rsidRDefault="00854A14" w:rsidP="00854A14"><w:pPr><w:pStyle w:val="Descripcin"/><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="009B44B4"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">Fig.  </w:t></w:r><w:r w:rsidRPr="009B44B4"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/></w:rPr><w:fldChar w:fldCharType="begin"/></w:r><w:r w:rsidRPr="009B44B4"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:instrText xml:space="preserve"> SEQ Fig._ \* ARABIC </w:instrText></w:r><w:r w:rsidRPr="009B44B4"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/></w:rPr><w:fldChar w:fldCharType="separate"/></w:r><w:r w:rsidR="0088649E"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:noProof/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t>3</w:t></w:r><w:r w:rsidRPr="009B44B4"><w:rPr><w:b/><w:bCs/><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/></w:rPr><w:fldChar w:fldCharType="end"/></w:r><w:r w:rsidRPr="009B44B4"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">. Infusion cannula placement as verified on Nissl stained sections of the IC (A) and AMY (B). SCR (○) and ODN (●) injector tips. Sections based on </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="009B44B4"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t>Paxinos</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="009B44B4"><w:rPr><w:i w:val="0"/><w:iCs w:val="0"/><w:color w:val="auto"/><w:sz w:val="16"/><w:szCs w:val="16"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> and Watson [13].</w:t></w:r></w:p><w:p w14:paraId="14971C67" w14:textId="77777777" w:rsidR="00272BA4" w:rsidRPr="0088649E" w:rsidRDefault="00272BA4" w:rsidP="00E7351C"><w:pPr><w:pStyle w:val="Ttulo2"/><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="0088649E"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Conflict of interest</w:t></w:r></w:p><w:p w14:paraId="04295A23" w14:textId="77777777" w:rsidR="00272BA4" w:rsidRPr="00067330" w:rsidRDefault="00272BA4" w:rsidP="00067330"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00067330"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">The authors declare no conflict of interest. </w:t></w:r></w:p><w:p w14:paraId="4173A577" w14:textId="77777777" w:rsidR="00272BA4" w:rsidRPr="00272BA4" w:rsidRDefault="00272BA4" w:rsidP="00272BA4"><w:pPr><w:rPr><w:sz w:val="22"/><w:lang w:val="en-US"/></w:rPr></w:pPr></w:p><w:p w14:paraId="0C9F9B47" w14:textId="77777777" w:rsidR="00272BA4" w:rsidRPr="0088649E" w:rsidRDefault="00272BA4" w:rsidP="00E7351C"><w:pPr><w:pStyle w:val="Ttulo2"/><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="0088649E"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Acknowledgements</w:t></w:r></w:p><w:p w14:paraId="6214AC7C" w14:textId="77777777" w:rsidR="00272BA4" w:rsidRPr="00E7351C" w:rsidRDefault="00272BA4" w:rsidP="00067330"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00E7351C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">This study was performed as part of the AV. Masters’ degree in Biology in Texas A&amp;M University. We thank Dr. Perla Moreno and Marisela Hernández Aguilar for technical assistance. This work was supported by grants from PRODEP (UAM-PTC-585) to K.G.R and by </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00E7351C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>CONACyT</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00E7351C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> (250870), </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00E7351C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Fronteras</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00E7351C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> de la </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00E7351C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>Ciencia</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00E7351C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> (474) and DGAPA PAPIITUNAM</w:t></w:r><w:r w:rsidR="00E7351C" w:rsidRPr="00E7351C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00E7351C"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>(IN208616) to F.B.R.</w:t></w:r></w:p><w:p w14:paraId="4E2A0C01" w14:textId="77777777" w:rsidR="00272BA4" w:rsidRPr="00272BA4" w:rsidRDefault="00272BA4" w:rsidP="00272BA4"><w:pPr><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr></w:p><w:p w14:paraId="3E1B5EFA" w14:textId="77777777" w:rsidR="00272BA4" w:rsidRPr="00272BA4" w:rsidRDefault="00272BA4" w:rsidP="00272BA4"><w:pPr><w:pStyle w:val="Ttulo2"/><w:rPr><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00272BA4"><w:rPr><w:lang w:val="en-US"/></w:rPr><w:t>References</w:t></w:r></w:p><w:p w14:paraId="3B1763C7" w14:textId="77777777" w:rsidR="00272BA4" w:rsidRPr="00067330" w:rsidRDefault="00272BA4" w:rsidP="00272BA4"><w:pPr><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>[1] F. 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Rev. </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>Neurosci</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>. 5 (3) (2004) 209–217.</w:t></w:r></w:p><w:p w14:paraId="0B5BA3A9" w14:textId="77777777" w:rsidR="00272BA4" w:rsidRPr="00067330" w:rsidRDefault="00272BA4" w:rsidP="00272BA4"><w:pPr><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:lastRenderedPageBreak/><w:t xml:space="preserve">[2] Y. </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>Yasoshima</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">, N. </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>Sako</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">, E. </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>Senba</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>, T. 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A. 103 (18) (2006) 7106–7111.</w:t></w:r></w:p><w:p w14:paraId="4C82A1CE" w14:textId="77777777" w:rsidR="00272BA4" w:rsidRPr="00067330" w:rsidRDefault="00272BA4" w:rsidP="00272BA4"><w:pPr><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">[3] A. Elkobi, I. Ehrlich, K. </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>Belelovsky</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">, L. </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>Barki</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">-Harrington, K. Rosenblum, ERK-dependent PSD-95 induction in the gustatory cortex is necessary for taste learning, but not retrieval, Nat. </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>Neurosci</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>. 11 (10) (2008) 1149–1151.</w:t></w:r></w:p><w:p w14:paraId="4A862CAF" w14:textId="77777777" w:rsidR="00272BA4" w:rsidRPr="00067330" w:rsidRDefault="00272BA4" w:rsidP="00272BA4"><w:pPr><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>[4] D.V. Castillo, Y. Figueroa-Guzman, M.L. Escobar, Brain-derived neurotrophic factor enhances conditioned taste aversion retention, Brain Res. 1067 (1) (2006) 250–255.</w:t></w:r></w:p><w:p w14:paraId="186D0F0B" w14:textId="77777777" w:rsidR="00272BA4" w:rsidRPr="00067330" w:rsidRDefault="00272BA4" w:rsidP="00272BA4"><w:pPr><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>[5] M.T. Koh, E.E. Wilkins, I.L. Bernstein, Novel tastes elevate c-</w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>fos</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> expression in the central amygdala and insular cortex: implication for taste aversion learning, </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>Behav</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>.</w:t></w:r></w:p><w:p w14:paraId="2AE6C7D4" w14:textId="77777777" w:rsidR="00272BA4" w:rsidRPr="00067330" w:rsidRDefault="00272BA4" w:rsidP="00272BA4"><w:pPr><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr></w:pPr><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>Neurosci</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>. 117 (6) (2003) 1416–1422.</w:t></w:r></w:p><w:p w14:paraId="728CD7A5" w14:textId="77777777" w:rsidR="00272BA4" w:rsidRPr="00067330" w:rsidRDefault="00272BA4" w:rsidP="00272BA4"><w:pPr><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">[6] T. Yamamoto, N. </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>Sako</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">, N. Sakai, A. </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>Iwafune</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>, Gustatory and visceral inputs to the amygdala of the rat: conditioned taste aversion and induction of c-</w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>fos</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">-like immunoreactivity, </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>Neurosci</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>. Lett. 226 (2) (1997) 127–130.</w:t></w:r></w:p><w:p w14:paraId="2039C7A9" w14:textId="77777777" w:rsidR="00272BA4" w:rsidRPr="00067330" w:rsidRDefault="00272BA4" w:rsidP="00272BA4"><w:pPr><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>[7] E.E. Wilkins, I.L. Bernstein, Conditioning method determines patterns of c-</w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>fos</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> expression</w:t></w:r><w:r w:rsidR="006F6592" w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">following novel taste-illness pairing, </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>Behav</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>. Brain Res. 169 (1) (2006)</w:t></w:r><w:r w:rsidR="006F6592" w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve"> </w:t></w:r><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>93–97.</w:t></w:r></w:p><w:p w14:paraId="63AD5577" w14:textId="77777777" w:rsidR="00272BA4" w:rsidRPr="00067330" w:rsidRDefault="00272BA4" w:rsidP="00272BA4"><w:pPr><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr></w:pPr><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">[8] S.K. </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>Barot</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t xml:space="preserve">, Y. </w:t></w:r><w:proofErr w:type="spellStart"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>Kyono</w:t></w:r><w:proofErr w:type="spellEnd"/><w:r w:rsidRPr="00067330"><w:rPr><w:sz w:val="18"/><w:szCs w:val="18"/><w:lang w:val="en-US"/></w:rPr><w:t>, E.W. 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