Cargando…
Brn3b regulates the formation of fear-related midbrain circuits and defensive responses to visual threat
Defensive responses to visually threatening stimuli represent an essential fear-related survival instinct, widely detected across species. The neural circuitry mediating visually triggered defensive responses has been delineated in the midbrain. However, the molecular mechanisms regulating the devel...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695396/ https://www.ncbi.nlm.nih.gov/pubmed/37983249 http://dx.doi.org/10.1371/journal.pbio.3002386 |
_version_ | 1785153557595422720 |
---|---|
author | Lee, Hyoseo Weinberg-Wolf, Hannah Lee, Hae-Lim Lee, Tracy Conte, Joseph Godoy-Parejo, Carlos Demb, Jonathan B. Rudenko, Andrii Kim, In-Jung |
author_facet | Lee, Hyoseo Weinberg-Wolf, Hannah Lee, Hae-Lim Lee, Tracy Conte, Joseph Godoy-Parejo, Carlos Demb, Jonathan B. Rudenko, Andrii Kim, In-Jung |
author_sort | Lee, Hyoseo |
collection | PubMed |
description | Defensive responses to visually threatening stimuli represent an essential fear-related survival instinct, widely detected across species. The neural circuitry mediating visually triggered defensive responses has been delineated in the midbrain. However, the molecular mechanisms regulating the development and function of these circuits remain unresolved. Here, we show that midbrain-specific deletion of the transcription factor Brn3b causes a loss of neurons projecting to the lateral posterior nucleus of the thalamus. Brn3b deletion also down-regulates the expression of the neuropeptide tachykinin 2 (Tac2). Furthermore, Brn3b mutant mice display impaired defensive freezing responses to visual threat precipitated by social isolation. This behavioral phenotype could be ameliorated by overexpressing Tac2, suggesting that Tac2 acts downstream of Brn3b in regulating defensive responses to threat. Together, our experiments identify specific genetic components critical for the functional organization of midbrain fear-related visual circuits. Similar mechanisms may contribute to the development and function of additional long-range brain circuits underlying fear-associated behavior. |
format | Online Article Text |
id | pubmed-10695396 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-106953962023-12-05 Brn3b regulates the formation of fear-related midbrain circuits and defensive responses to visual threat Lee, Hyoseo Weinberg-Wolf, Hannah Lee, Hae-Lim Lee, Tracy Conte, Joseph Godoy-Parejo, Carlos Demb, Jonathan B. Rudenko, Andrii Kim, In-Jung PLoS Biol Research Article Defensive responses to visually threatening stimuli represent an essential fear-related survival instinct, widely detected across species. The neural circuitry mediating visually triggered defensive responses has been delineated in the midbrain. However, the molecular mechanisms regulating the development and function of these circuits remain unresolved. Here, we show that midbrain-specific deletion of the transcription factor Brn3b causes a loss of neurons projecting to the lateral posterior nucleus of the thalamus. Brn3b deletion also down-regulates the expression of the neuropeptide tachykinin 2 (Tac2). Furthermore, Brn3b mutant mice display impaired defensive freezing responses to visual threat precipitated by social isolation. This behavioral phenotype could be ameliorated by overexpressing Tac2, suggesting that Tac2 acts downstream of Brn3b in regulating defensive responses to threat. Together, our experiments identify specific genetic components critical for the functional organization of midbrain fear-related visual circuits. Similar mechanisms may contribute to the development and function of additional long-range brain circuits underlying fear-associated behavior. Public Library of Science 2023-11-20 /pmc/articles/PMC10695396/ /pubmed/37983249 http://dx.doi.org/10.1371/journal.pbio.3002386 Text en © 2023 Lee et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Lee, Hyoseo Weinberg-Wolf, Hannah Lee, Hae-Lim Lee, Tracy Conte, Joseph Godoy-Parejo, Carlos Demb, Jonathan B. Rudenko, Andrii Kim, In-Jung Brn3b regulates the formation of fear-related midbrain circuits and defensive responses to visual threat |
title | Brn3b regulates the formation of fear-related midbrain circuits and defensive responses to visual threat |
title_full | Brn3b regulates the formation of fear-related midbrain circuits and defensive responses to visual threat |
title_fullStr | Brn3b regulates the formation of fear-related midbrain circuits and defensive responses to visual threat |
title_full_unstemmed | Brn3b regulates the formation of fear-related midbrain circuits and defensive responses to visual threat |
title_short | Brn3b regulates the formation of fear-related midbrain circuits and defensive responses to visual threat |
title_sort | brn3b regulates the formation of fear-related midbrain circuits and defensive responses to visual threat |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695396/ https://www.ncbi.nlm.nih.gov/pubmed/37983249 http://dx.doi.org/10.1371/journal.pbio.3002386 |
work_keys_str_mv | AT leehyoseo brn3bregulatestheformationoffearrelatedmidbraincircuitsanddefensiveresponsestovisualthreat AT weinbergwolfhannah brn3bregulatestheformationoffearrelatedmidbraincircuitsanddefensiveresponsestovisualthreat AT leehaelim brn3bregulatestheformationoffearrelatedmidbraincircuitsanddefensiveresponsestovisualthreat AT leetracy brn3bregulatestheformationoffearrelatedmidbraincircuitsanddefensiveresponsestovisualthreat AT contejoseph brn3bregulatestheformationoffearrelatedmidbraincircuitsanddefensiveresponsestovisualthreat AT godoyparejocarlos brn3bregulatestheformationoffearrelatedmidbraincircuitsanddefensiveresponsestovisualthreat AT dembjonathanb brn3bregulatestheformationoffearrelatedmidbraincircuitsanddefensiveresponsestovisualthreat AT rudenkoandrii brn3bregulatestheformationoffearrelatedmidbraincircuitsanddefensiveresponsestovisualthreat AT kiminjung brn3bregulatestheformationoffearrelatedmidbraincircuitsanddefensiveresponsestovisualthreat |