Somatostatin Neurons of the Bed Nucleus of Stria Terminalis Enhance Associative Fear Memory Consolidation in Mice
Excessive fear learning and generalized, extinction-resistant fear memories are core symptoms of anxiety and trauma-related disorders. Despite significant evidence from clinical studies reporting hyperactivity of the bed nucleus of stria terminalis (BNST) under these conditions, the role of BNST in...
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Veröffentlicht in: | The Journal of neuroscience 2021-03, Vol.41 (9), p.1982-1995 |
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container_end_page | 1995 |
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container_issue | 9 |
container_start_page | 1982 |
container_title | The Journal of neuroscience |
container_volume | 41 |
creator | Bruzsik, Biborka Biro, Laszlo Zelena, Dora Sipos, Eszter Szebik, Huba Sarosdi, Klara Rebeka Horvath, Orsolya Farkas, Imre Csillag, Veronika Finszter, Cintia Klaudia Mikics, Eva Toth, Mate |
description | Excessive fear learning and generalized, extinction-resistant fear memories are core symptoms of anxiety and trauma-related disorders. Despite significant evidence from clinical studies reporting hyperactivity of the bed nucleus of stria terminalis (BNST) under these conditions, the role of BNST in fear learning and expression is still not clarified. Here, we tested how BNST modulates fear learning in male mice using a chemogenetic approach. Activation of GABAergic neurons of BNST during fear conditioning or memory consolidation resulted in enhanced cue-related fear recall. Importantly, BNST activation had no acute impact on fear expression during conditioning or recalls, but it enhanced cue-related fear recall subsequently, potentially via altered activity of downstream regions. Enhanced fear memory consolidation could be replicated by selectively activating somatostatin (SOM), but not corticotropin-releasing factor (CRF), neurons of the BNST, which was accompanied by increased fear generalization. Our findings suggest the significant modulation of fear memory strength by specific circuits of the BNST. |
doi_str_mv | 10.1523/JNEUROSCI.1944-20.2020 |
format | Article |
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Despite significant evidence from clinical studies reporting hyperactivity of the bed nucleus of stria terminalis (BNST) under these conditions, the role of BNST in fear learning and expression is still not clarified. Here, we tested how BNST modulates fear learning in male mice using a chemogenetic approach. Activation of GABAergic neurons of BNST during fear conditioning or memory consolidation resulted in enhanced cue-related fear recall. Importantly, BNST activation had no acute impact on fear expression during conditioning or recalls, but it enhanced cue-related fear recall subsequently, potentially via altered activity of downstream regions. Enhanced fear memory consolidation could be replicated by selectively activating somatostatin (SOM), but not corticotropin-releasing factor (CRF), neurons of the BNST, which was accompanied by increased fear generalization. Our findings suggest the significant modulation of fear memory strength by specific circuits of the BNST.</description><identifier>ISSN: 0270-6474</identifier><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/JNEUROSCI.1944-20.2020</identifier><identifier>PMID: 33468566</identifier><language>eng</language><publisher>WASHINGTON: Soc Neuroscience</publisher><subject>Animal memory ; Associative memory ; Consolidation ; Corticotropin-releasing hormone ; Fear ; Fear conditioning ; Hyperactivity ; Learning ; Life Sciences & Biomedicine ; Neurons ; Neurosciences ; Neurosciences & Neurology ; Recall ; Science & Technology ; Signs and symptoms ; Somatostatin ; Stria terminalis ; Trauma ; γ-Aminobutyric acid</subject><ispartof>The Journal of neuroscience, 2021-03, Vol.41 (9), p.1982-1995</ispartof><rights>Copyright © 2021 the authors.</rights><rights>Copyright Society for Neuroscience Mar 3, 2021</rights><rights>Copyright © 2021 the authors 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>14</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000631722100001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c508t-ebda4d4c351175a278cadf269d4dcf4911c6e975dab64281861e83a5cdb68e33</citedby><cites>FETCH-LOGICAL-c508t-ebda4d4c351175a278cadf269d4dcf4911c6e975dab64281861e83a5cdb68e33</cites><orcidid>0000-0002-0159-4408 ; 0000-0001-6382-5999 ; 0000-0003-4951-4929 ; 0000-0003-2417-4489 ; 0000-0002-7688-2033 ; 0000-0001-5616-1100</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939080/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939080/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27929,27930,39263,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33468566$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bruzsik, Biborka</creatorcontrib><creatorcontrib>Biro, Laszlo</creatorcontrib><creatorcontrib>Zelena, Dora</creatorcontrib><creatorcontrib>Sipos, Eszter</creatorcontrib><creatorcontrib>Szebik, Huba</creatorcontrib><creatorcontrib>Sarosdi, Klara Rebeka</creatorcontrib><creatorcontrib>Horvath, Orsolya</creatorcontrib><creatorcontrib>Farkas, Imre</creatorcontrib><creatorcontrib>Csillag, Veronika</creatorcontrib><creatorcontrib>Finszter, Cintia Klaudia</creatorcontrib><creatorcontrib>Mikics, Eva</creatorcontrib><creatorcontrib>Toth, Mate</creatorcontrib><title>Somatostatin Neurons of the Bed Nucleus of Stria Terminalis Enhance Associative Fear Memory Consolidation in Mice</title><title>The Journal of neuroscience</title><addtitle>J NEUROSCI</addtitle><addtitle>J Neurosci</addtitle><description>Excessive fear learning and generalized, extinction-resistant fear memories are core symptoms of anxiety and trauma-related disorders. 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Our findings suggest the significant modulation of fear memory strength by specific circuits of the BNST.</description><subject>Animal memory</subject><subject>Associative memory</subject><subject>Consolidation</subject><subject>Corticotropin-releasing hormone</subject><subject>Fear</subject><subject>Fear conditioning</subject><subject>Hyperactivity</subject><subject>Learning</subject><subject>Life Sciences & Biomedicine</subject><subject>Neurons</subject><subject>Neurosciences</subject><subject>Neurosciences & Neurology</subject><subject>Recall</subject><subject>Science & Technology</subject><subject>Signs and symptoms</subject><subject>Somatostatin</subject><subject>Stria terminalis</subject><subject>Trauma</subject><subject>γ-Aminobutyric acid</subject><issn>0270-6474</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><recordid>eNqNkV1v0zAUhiMEYmXwFyZL3CChFH_FTm6QRtSNoa2TaLm2XPuEekrszU6G9u_nrqMCrriy5fOc18d-iuKE4DmpKPv0bbn48f161V7MScN5SfGcYopfFLNcbUrKMXlZzDCVuBRc8qPiTUo3GGOJiXxdHDHGRV0JMSvuVmHQY0ijHp1HS5hi8AmFDo1bQF_AouVkepiejlZjdBqtIQ7O694ltPBb7Q2g05SCcTnhHtAZ6IiuYAjxAbU5K_TO5krwKOdfOQNvi1ed7hO8e16Pi_XZYt1-LS-vzy_a08vSVLgeS9hYzS03rCJEVprK2mjbUdFYbk3HG0KMgEZWVm8EpzWpBYGa6crYjaiBsePi8z72dtoMYA34Mepe3UY36Piggnbq74p3W_Uz3CvZsAbXOAd8eA6I4W6CNKrBJQN9rz2EKSnKZcMpy1dn9P0_6E2YYv6jTFWYsxpTKjMl9pSJIaUI3WEYgtVOqjpIVTupimK1k5obT_58yqHtt8UMfNwDv2ATumQcZCsHLGsXjEhKSd7h3bT1_9OtG5_stWHyI3sEZtnA3w</recordid><startdate>20210303</startdate><enddate>20210303</enddate><creator>Bruzsik, Biborka</creator><creator>Biro, Laszlo</creator><creator>Zelena, Dora</creator><creator>Sipos, Eszter</creator><creator>Szebik, Huba</creator><creator>Sarosdi, Klara Rebeka</creator><creator>Horvath, Orsolya</creator><creator>Farkas, Imre</creator><creator>Csillag, Veronika</creator><creator>Finszter, Cintia Klaudia</creator><creator>Mikics, Eva</creator><creator>Toth, Mate</creator><general>Soc Neuroscience</general><general>Society for Neuroscience</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0159-4408</orcidid><orcidid>https://orcid.org/0000-0001-6382-5999</orcidid><orcidid>https://orcid.org/0000-0003-4951-4929</orcidid><orcidid>https://orcid.org/0000-0003-2417-4489</orcidid><orcidid>https://orcid.org/0000-0002-7688-2033</orcidid><orcidid>https://orcid.org/0000-0001-5616-1100</orcidid></search><sort><creationdate>20210303</creationdate><title>Somatostatin Neurons of the Bed Nucleus of Stria Terminalis Enhance Associative Fear Memory Consolidation in Mice</title><author>Bruzsik, Biborka ; 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subjects | Animal memory Associative memory Consolidation Corticotropin-releasing hormone Fear Fear conditioning Hyperactivity Learning Life Sciences & Biomedicine Neurons Neurosciences Neurosciences & Neurology Recall Science & Technology Signs and symptoms Somatostatin Stria terminalis Trauma γ-Aminobutyric acid |
title | Somatostatin Neurons of the Bed Nucleus of Stria Terminalis Enhance Associative Fear Memory Consolidation in Mice |
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