Manipulating fear associations via optogenetic modulation of amygdala inputs to prefrontal cortex
Fear-related disorders are thought to reflect strong and persistent fear associations. The authors show that optogenetic high-frequency stimulation of direct amygdala inputs to the prefrontal cortex can destabilize fear memories and facilitate the extinction of previously acquired fear associations....
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| Veröffentlicht in: | Nature neuroscience 2017-06, Vol.20 (6), p.836-844 |
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| creator | Klavir, Oded Prigge, Matthias Sarel, Ayelet Paz, Rony Yizhar, Ofer |
| description | Fear-related disorders are thought to reflect strong and persistent fear associations. The authors show that optogenetic high-frequency stimulation of direct amygdala inputs to the prefrontal cortex can destabilize fear memories and facilitate the extinction of previously acquired fear associations.
Fear-related disorders are thought to reflect strong and persistent fear memories. The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) form strong reciprocal synaptic connections that play a key role in acquisition and extinction of fear memories. While synaptic contacts of BLA cells onto mPFC neurons are likely to play a crucial role in this process, the BLA connects with several additional nuclei within the fear circuit that could relay fear-associated information to the mPFC, and the contribution of direct monosynaptic BLA–mPFC inputs is not yet clear. Here we establish an optogenetic stimulation protocol that induces synaptic depression in BLA–mPFC synapses. In behaving mice, optogenetic high-frequency stimulation of BLA inputs to mPFC interfered with retention of cued associations, attenuated previously acquired cue-associated responses in mPFC neurons and facilitated extinction. Our findings demonstrate the contribution of BLA inputs to mPFC in forming and maintaining cued fear associations. |
| doi_str_mv | 10.1038/nn.4523 |
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Fear-related disorders are thought to reflect strong and persistent fear memories. The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) form strong reciprocal synaptic connections that play a key role in acquisition and extinction of fear memories. While synaptic contacts of BLA cells onto mPFC neurons are likely to play a crucial role in this process, the BLA connects with several additional nuclei within the fear circuit that could relay fear-associated information to the mPFC, and the contribution of direct monosynaptic BLA–mPFC inputs is not yet clear. Here we establish an optogenetic stimulation protocol that induces synaptic depression in BLA–mPFC synapses. In behaving mice, optogenetic high-frequency stimulation of BLA inputs to mPFC interfered with retention of cued associations, attenuated previously acquired cue-associated responses in mPFC neurons and facilitated extinction. Our findings demonstrate the contribution of BLA inputs to mPFC in forming and maintaining cued fear associations.</description><identifier>ISSN: 1097-6256</identifier><identifier>EISSN: 1546-1726</identifier><identifier>DOI: 10.1038/nn.4523</identifier><identifier>PMID: 28288126</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>13 ; 14 ; 631/378/1457/1284 ; 631/378/1457/1945 ; 631/378/1595 ; 631/378/1595/2636 ; 631/378/3920 ; 9/74 ; Amygdala ; Amygdala (Brain) ; Amygdala - physiology ; Analysis ; Animal Genetics and Genomics ; Animals ; Behavioral Sciences ; Biological Techniques ; Biomedicine ; Conditioning (Psychology) - physiology ; Disorders ; Extinction behavior ; Extinction, Psychological - physiology ; Fear ; Fear - physiology ; Kinases ; Light ; Long-Term Synaptic Depression - physiology ; Male ; Memory ; Memory - physiology ; Mice ; Mice, Transgenic ; Mouse devices ; Neural Pathways - physiology ; Neurobiology ; Neurons ; Neurons - physiology ; Neurosciences ; Nuclei ; Optogenetics - methods ; Prefrontal cortex ; Prefrontal Cortex - physiology ; Protocol ; Stimulation ; Synapses ; Synaptic depression</subject><ispartof>Nature neuroscience, 2017-06, Vol.20 (6), p.836-844</ispartof><rights>Springer Nature America, Inc. 2017</rights><rights>COPYRIGHT 2017 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-65dbcec0ba3c4ca9d01f3bcfb7e7b813468904db97d75e4d414b18da15917c7f3</citedby><cites>FETCH-LOGICAL-c509t-65dbcec0ba3c4ca9d01f3bcfb7e7b813468904db97d75e4d414b18da15917c7f3</cites><orcidid>0000-0003-4228-1448</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nn.4523$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nn.4523$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28288126$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Klavir, Oded</creatorcontrib><creatorcontrib>Prigge, Matthias</creatorcontrib><creatorcontrib>Sarel, Ayelet</creatorcontrib><creatorcontrib>Paz, Rony</creatorcontrib><creatorcontrib>Yizhar, Ofer</creatorcontrib><title>Manipulating fear associations via optogenetic modulation of amygdala inputs to prefrontal cortex</title><title>Nature neuroscience</title><addtitle>Nat Neurosci</addtitle><addtitle>Nat Neurosci</addtitle><description>Fear-related disorders are thought to reflect strong and persistent fear associations. The authors show that optogenetic high-frequency stimulation of direct amygdala inputs to the prefrontal cortex can destabilize fear memories and facilitate the extinction of previously acquired fear associations.
Fear-related disorders are thought to reflect strong and persistent fear memories. The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) form strong reciprocal synaptic connections that play a key role in acquisition and extinction of fear memories. While synaptic contacts of BLA cells onto mPFC neurons are likely to play a crucial role in this process, the BLA connects with several additional nuclei within the fear circuit that could relay fear-associated information to the mPFC, and the contribution of direct monosynaptic BLA–mPFC inputs is not yet clear. Here we establish an optogenetic stimulation protocol that induces synaptic depression in BLA–mPFC synapses. In behaving mice, optogenetic high-frequency stimulation of BLA inputs to mPFC interfered with retention of cued associations, attenuated previously acquired cue-associated responses in mPFC neurons and facilitated extinction. Our findings demonstrate the contribution of BLA inputs to mPFC in forming and maintaining cued fear associations.</description><subject>13</subject><subject>14</subject><subject>631/378/1457/1284</subject><subject>631/378/1457/1945</subject><subject>631/378/1595</subject><subject>631/378/1595/2636</subject><subject>631/378/3920</subject><subject>9/74</subject><subject>Amygdala</subject><subject>Amygdala (Brain)</subject><subject>Amygdala - physiology</subject><subject>Analysis</subject><subject>Animal Genetics and Genomics</subject><subject>Animals</subject><subject>Behavioral Sciences</subject><subject>Biological Techniques</subject><subject>Biomedicine</subject><subject>Conditioning (Psychology) - physiology</subject><subject>Disorders</subject><subject>Extinction behavior</subject><subject>Extinction, Psychological - physiology</subject><subject>Fear</subject><subject>Fear - physiology</subject><subject>Kinases</subject><subject>Light</subject><subject>Long-Term Synaptic Depression - 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Academic</collection><jtitle>Nature neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Klavir, Oded</au><au>Prigge, Matthias</au><au>Sarel, Ayelet</au><au>Paz, Rony</au><au>Yizhar, Ofer</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Manipulating fear associations via optogenetic modulation of amygdala inputs to prefrontal cortex</atitle><jtitle>Nature neuroscience</jtitle><stitle>Nat Neurosci</stitle><addtitle>Nat Neurosci</addtitle><date>2017-06-01</date><risdate>2017</risdate><volume>20</volume><issue>6</issue><spage>836</spage><epage>844</epage><pages>836-844</pages><issn>1097-6256</issn><eissn>1546-1726</eissn><abstract>Fear-related disorders are thought to reflect strong and persistent fear associations. The authors show that optogenetic high-frequency stimulation of direct amygdala inputs to the prefrontal cortex can destabilize fear memories and facilitate the extinction of previously acquired fear associations.
Fear-related disorders are thought to reflect strong and persistent fear memories. The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) form strong reciprocal synaptic connections that play a key role in acquisition and extinction of fear memories. While synaptic contacts of BLA cells onto mPFC neurons are likely to play a crucial role in this process, the BLA connects with several additional nuclei within the fear circuit that could relay fear-associated information to the mPFC, and the contribution of direct monosynaptic BLA–mPFC inputs is not yet clear. Here we establish an optogenetic stimulation protocol that induces synaptic depression in BLA–mPFC synapses. In behaving mice, optogenetic high-frequency stimulation of BLA inputs to mPFC interfered with retention of cued associations, attenuated previously acquired cue-associated responses in mPFC neurons and facilitated extinction. Our findings demonstrate the contribution of BLA inputs to mPFC in forming and maintaining cued fear associations.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>28288126</pmid><doi>10.1038/nn.4523</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-4228-1448</orcidid></addata></record> |
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| subjects | 13 14 631/378/1457/1284 631/378/1457/1945 631/378/1595 631/378/1595/2636 631/378/3920 9/74 Amygdala Amygdala (Brain) Amygdala - physiology Analysis Animal Genetics and Genomics Animals Behavioral Sciences Biological Techniques Biomedicine Conditioning (Psychology) - physiology Disorders Extinction behavior Extinction, Psychological - physiology Fear Fear - physiology Kinases Light Long-Term Synaptic Depression - physiology Male Memory Memory - physiology Mice Mice, Transgenic Mouse devices Neural Pathways - physiology Neurobiology Neurons Neurons - physiology Neurosciences Nuclei Optogenetics - methods Prefrontal cortex Prefrontal Cortex - physiology Protocol Stimulation Synapses Synaptic depression |
| title | Manipulating fear associations via optogenetic modulation of amygdala inputs to prefrontal cortex |
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