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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...

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Autores principales: Lee, Hyoseo, Weinberg-Wolf, Hannah, Lee, Hae-Lim, Lee, Tracy, Conte, Joseph, Godoy-Parejo, Carlos, Demb, Jonathan B., Rudenko, Andrii, Kim, In-Jung
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
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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.
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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
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