Ghrelin infusion into the basolateral amygdala suppresses CTA memory formation in rats via the PI3K/Akt/mTOR and PLC/PKC signaling pathways
Ghrelin is a circulating orexigenic hormone that promotes feeding behavior and regulates metabolism in humans and rodents. We previously reported that local infusion of ghrelin into the basolateral amygdala (BLA) blocked memory acquisition for conditioned taste aversion (CTA) by activating growth ho...
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| Veröffentlicht in: | Acta pharmacologica Sinica 2022-09, Vol.43 (9), p.2242-2252 |
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| creator | Yu, Ming Zhu, Qian-qian Niu, Ming-lu Li, Nan Ren, Bai-qing Yu, Teng-bo Zhou, Zhi-shang Guo, Ji-dong Zhou, Yu |
| description | Ghrelin is a circulating orexigenic hormone that promotes feeding behavior and regulates metabolism in humans and rodents. We previously reported that local infusion of ghrelin into the basolateral amygdala (BLA) blocked memory acquisition for conditioned taste aversion (CTA) by activating growth hormone secretagogue receptor 1a. In this study, we further explored the underlying mechanism and signaling pathways mediating ghrelin modulation of CTA memory in rats. Pharmacological agents targeting distinct signaling pathways were infused into the BLA during conditioning. We showed that preadministration of the PI3K inhibitor LY294002 abolished the repressive effect of ghrelin on CTA memory. Moreover, LY294002 pretreatment prevented ghrelin from inhibiting
Arc
and
zif268
mRNA expression in the BLA triggered by CTA memory retrieval. Preadministration of rapamycin eliminated the repressive effect of ghrelin, while Gsk3 inhibitors failed to mimic ghrelin’s effect. In addition, PLC and PKC inhibitors microinfused in the BLA blocked ghrelin’s repression of CTA acquisition. These results demonstrate that ghrelin signaling in the BLA shapes CTA memory via the PI3K/Akt/mTOR and PLC/PKC pathways. We conducted in vivo multichannel recordings from mouse BLA neurons and found that microinjection of ghrelin (20 µM) suppressed intrinsic excitability. By means of whole-cell recordings from rat brain slices, we showed that bath application of ghrelin (200 nM) had no effect on basal synaptic transmission or synaptic plasticity of BLA pyramidal neurons. Together, this study reveals the mechanism underlying ghrelin-induced interference with CTA memory acquisition in rats, i.e., suppression of intrinsic excitability of BLA principal neurons via the PI3K/Akt/mTOR and PLC/PKC pathways. |
| doi_str_mv | 10.1038/s41401-022-00859-w |
| format | Article |
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Arc
and
zif268
mRNA expression in the BLA triggered by CTA memory retrieval. Preadministration of rapamycin eliminated the repressive effect of ghrelin, while Gsk3 inhibitors failed to mimic ghrelin’s effect. In addition, PLC and PKC inhibitors microinfused in the BLA blocked ghrelin’s repression of CTA acquisition. These results demonstrate that ghrelin signaling in the BLA shapes CTA memory via the PI3K/Akt/mTOR and PLC/PKC pathways. We conducted in vivo multichannel recordings from mouse BLA neurons and found that microinjection of ghrelin (20 µM) suppressed intrinsic excitability. By means of whole-cell recordings from rat brain slices, we showed that bath application of ghrelin (200 nM) had no effect on basal synaptic transmission or synaptic plasticity of BLA pyramidal neurons. Together, this study reveals the mechanism underlying ghrelin-induced interference with CTA memory acquisition in rats, i.e., suppression of intrinsic excitability of BLA principal neurons via the PI3K/Akt/mTOR and PLC/PKC pathways.</description><identifier>ISSN: 1671-4083</identifier><identifier>EISSN: 1745-7254</identifier><identifier>DOI: 10.1038/s41401-022-00859-w</identifier><identifier>PMID: 35169271</identifier><language>eng</language><publisher>Singapore: Springer Nature Singapore</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Amygdala ; Biomedical and Life Sciences ; Biomedicine ; Brain slice preparation ; Dopamine ; EGR-1 protein ; Excitability ; Experiments ; Feeding behavior ; Gene expression ; Ghrelin ; Growth hormones ; Homeostasis ; Immunology ; Internal Medicine ; Kinases ; Laboratory animals ; Life sciences ; Medical Microbiology ; Medical research ; Metabolism ; Microinjection ; Pharmacology/Toxicology ; Proteins ; Pyramidal cells ; Rapamycin ; Signal transduction ; Stainless steel ; Synaptic plasticity ; Synaptic transmission ; Taste aversion ; TOR protein ; Vaccine</subject><ispartof>Acta pharmacologica Sinica, 2022-09, Vol.43 (9), p.2242-2252</ispartof><rights>The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society 2022</rights><rights>2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.</rights><rights>The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society 2022.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-ba10f098c1fc1db19353a1a1e4f1bcecd4ab2ce0fb6c8a315d6df6e6fbb7cc2b3</citedby><cites>FETCH-LOGICAL-c474t-ba10f098c1fc1db19353a1a1e4f1bcecd4ab2ce0fb6c8a315d6df6e6fbb7cc2b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9433413/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9433413/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35169271$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, Ming</creatorcontrib><creatorcontrib>Zhu, Qian-qian</creatorcontrib><creatorcontrib>Niu, Ming-lu</creatorcontrib><creatorcontrib>Li, Nan</creatorcontrib><creatorcontrib>Ren, Bai-qing</creatorcontrib><creatorcontrib>Yu, Teng-bo</creatorcontrib><creatorcontrib>Zhou, Zhi-shang</creatorcontrib><creatorcontrib>Guo, Ji-dong</creatorcontrib><creatorcontrib>Zhou, Yu</creatorcontrib><title>Ghrelin infusion into the basolateral amygdala suppresses CTA memory formation in rats via the PI3K/Akt/mTOR and PLC/PKC signaling pathways</title><title>Acta pharmacologica Sinica</title><addtitle>Acta Pharmacol Sin</addtitle><addtitle>Acta Pharmacol Sin</addtitle><description>Ghrelin is a circulating orexigenic hormone that promotes feeding behavior and regulates metabolism in humans and rodents. We previously reported that local infusion of ghrelin into the basolateral amygdala (BLA) blocked memory acquisition for conditioned taste aversion (CTA) by activating growth hormone secretagogue receptor 1a. In this study, we further explored the underlying mechanism and signaling pathways mediating ghrelin modulation of CTA memory in rats. Pharmacological agents targeting distinct signaling pathways were infused into the BLA during conditioning. We showed that preadministration of the PI3K inhibitor LY294002 abolished the repressive effect of ghrelin on CTA memory. Moreover, LY294002 pretreatment prevented ghrelin from inhibiting
Arc
and
zif268
mRNA expression in the BLA triggered by CTA memory retrieval. Preadministration of rapamycin eliminated the repressive effect of ghrelin, while Gsk3 inhibitors failed to mimic ghrelin’s effect. In addition, PLC and PKC inhibitors microinfused in the BLA blocked ghrelin’s repression of CTA acquisition. These results demonstrate that ghrelin signaling in the BLA shapes CTA memory via the PI3K/Akt/mTOR and PLC/PKC pathways. We conducted in vivo multichannel recordings from mouse BLA neurons and found that microinjection of ghrelin (20 µM) suppressed intrinsic excitability. By means of whole-cell recordings from rat brain slices, we showed that bath application of ghrelin (200 nM) had no effect on basal synaptic transmission or synaptic plasticity of BLA pyramidal neurons. Together, this study reveals the mechanism underlying ghrelin-induced interference with CTA memory acquisition in rats, i.e., suppression of intrinsic excitability of BLA principal neurons via the PI3K/Akt/mTOR and PLC/PKC pathways.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Amygdala</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain slice preparation</subject><subject>Dopamine</subject><subject>EGR-1 protein</subject><subject>Excitability</subject><subject>Experiments</subject><subject>Feeding behavior</subject><subject>Gene expression</subject><subject>Ghrelin</subject><subject>Growth hormones</subject><subject>Homeostasis</subject><subject>Immunology</subject><subject>Internal Medicine</subject><subject>Kinases</subject><subject>Laboratory animals</subject><subject>Life sciences</subject><subject>Medical Microbiology</subject><subject>Medical research</subject><subject>Metabolism</subject><subject>Microinjection</subject><subject>Pharmacology/Toxicology</subject><subject>Proteins</subject><subject>Pyramidal cells</subject><subject>Rapamycin</subject><subject>Signal transduction</subject><subject>Stainless steel</subject><subject>Synaptic plasticity</subject><subject>Synaptic transmission</subject><subject>Taste aversion</subject><subject>TOR 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CTA memory formation in rats via the PI3K/Akt/mTOR and PLC/PKC signaling pathways</title><author>Yu, Ming ; Zhu, Qian-qian ; Niu, Ming-lu ; Li, Nan ; Ren, Bai-qing ; Yu, Teng-bo ; Zhou, Zhi-shang ; Guo, Ji-dong ; Zhou, Yu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-ba10f098c1fc1db19353a1a1e4f1bcecd4ab2ce0fb6c8a315d6df6e6fbb7cc2b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Amygdala</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain slice preparation</topic><topic>Dopamine</topic><topic>EGR-1 protein</topic><topic>Excitability</topic><topic>Experiments</topic><topic>Feeding behavior</topic><topic>Gene expression</topic><topic>Ghrelin</topic><topic>Growth hormones</topic><topic>Homeostasis</topic><topic>Immunology</topic><topic>Internal Medicine</topic><topic>Kinases</topic><topic>Laboratory animals</topic><topic>Life sciences</topic><topic>Medical Microbiology</topic><topic>Medical research</topic><topic>Metabolism</topic><topic>Microinjection</topic><topic>Pharmacology/Toxicology</topic><topic>Proteins</topic><topic>Pyramidal cells</topic><topic>Rapamycin</topic><topic>Signal transduction</topic><topic>Stainless steel</topic><topic>Synaptic plasticity</topic><topic>Synaptic transmission</topic><topic>Taste aversion</topic><topic>TOR protein</topic><topic>Vaccine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Ming</creatorcontrib><creatorcontrib>Zhu, Qian-qian</creatorcontrib><creatorcontrib>Niu, Ming-lu</creatorcontrib><creatorcontrib>Li, Nan</creatorcontrib><creatorcontrib>Ren, Bai-qing</creatorcontrib><creatorcontrib>Yu, Teng-bo</creatorcontrib><creatorcontrib>Zhou, Zhi-shang</creatorcontrib><creatorcontrib>Guo, Ji-dong</creatorcontrib><creatorcontrib>Zhou, 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the basolateral amygdala suppresses CTA memory formation in rats via the PI3K/Akt/mTOR and PLC/PKC signaling pathways</atitle><jtitle>Acta pharmacologica Sinica</jtitle><stitle>Acta Pharmacol Sin</stitle><addtitle>Acta Pharmacol Sin</addtitle><date>2022-09-01</date><risdate>2022</risdate><volume>43</volume><issue>9</issue><spage>2242</spage><epage>2252</epage><pages>2242-2252</pages><issn>1671-4083</issn><eissn>1745-7254</eissn><abstract>Ghrelin is a circulating orexigenic hormone that promotes feeding behavior and regulates metabolism in humans and rodents. We previously reported that local infusion of ghrelin into the basolateral amygdala (BLA) blocked memory acquisition for conditioned taste aversion (CTA) by activating growth hormone secretagogue receptor 1a. In this study, we further explored the underlying mechanism and signaling pathways mediating ghrelin modulation of CTA memory in rats. Pharmacological agents targeting distinct signaling pathways were infused into the BLA during conditioning. We showed that preadministration of the PI3K inhibitor LY294002 abolished the repressive effect of ghrelin on CTA memory. Moreover, LY294002 pretreatment prevented ghrelin from inhibiting
Arc
and
zif268
mRNA expression in the BLA triggered by CTA memory retrieval. Preadministration of rapamycin eliminated the repressive effect of ghrelin, while Gsk3 inhibitors failed to mimic ghrelin’s effect. In addition, PLC and PKC inhibitors microinfused in the BLA blocked ghrelin’s repression of CTA acquisition. These results demonstrate that ghrelin signaling in the BLA shapes CTA memory via the PI3K/Akt/mTOR and PLC/PKC pathways. We conducted in vivo multichannel recordings from mouse BLA neurons and found that microinjection of ghrelin (20 µM) suppressed intrinsic excitability. By means of whole-cell recordings from rat brain slices, we showed that bath application of ghrelin (200 nM) had no effect on basal synaptic transmission or synaptic plasticity of BLA pyramidal neurons. Together, this study reveals the mechanism underlying ghrelin-induced interference with CTA memory acquisition in rats, i.e., suppression of intrinsic excitability of BLA principal neurons via the PI3K/Akt/mTOR and PLC/PKC pathways.</abstract><cop>Singapore</cop><pub>Springer Nature Singapore</pub><pmid>35169271</pmid><doi>10.1038/s41401-022-00859-w</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 1-Phosphatidylinositol 3-kinase AKT protein Amygdala Biomedical and Life Sciences Biomedicine Brain slice preparation Dopamine EGR-1 protein Excitability Experiments Feeding behavior Gene expression Ghrelin Growth hormones Homeostasis Immunology Internal Medicine Kinases Laboratory animals Life sciences Medical Microbiology Medical research Metabolism Microinjection Pharmacology/Toxicology Proteins Pyramidal cells Rapamycin Signal transduction Stainless steel Synaptic plasticity Synaptic transmission Taste aversion TOR protein Vaccine |
| title | Ghrelin infusion into the basolateral amygdala suppresses CTA memory formation in rats via the PI3K/Akt/mTOR and PLC/PKC signaling pathways |
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