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Genetic Tagging Uncovers a Robust, Selective Activation of the Thalamic Paraventricular Nucleus by Adverse Experiences Early in Life
BACKGROUND: Early-life adversity (ELA) is associated with increased risk for mood disorders, including depression and substance use disorders. These disorders are characterized by impaired reward-related behaviors, suggesting compromised operations of reward-related brain circuits. However, the brai...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593902/ https://www.ncbi.nlm.nih.gov/pubmed/37881549 http://dx.doi.org/10.1016/j.bpsgos.2023.01.002 |
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author | Kooiker, Cassandra L. Chen, Yuncai Birnie, Matthew T. Baram, Tallie Z. |
author_facet | Kooiker, Cassandra L. Chen, Yuncai Birnie, Matthew T. Baram, Tallie Z. |
author_sort | Kooiker, Cassandra L. |
collection | PubMed |
description | BACKGROUND: Early-life adversity (ELA) is associated with increased risk for mood disorders, including depression and substance use disorders. These disorders are characterized by impaired reward-related behaviors, suggesting compromised operations of reward-related brain circuits. However, the brain regions engaged by ELA that mediate these enduring consequences of ELA remain largely unknown. In an animal model of ELA, we identified aberrant reward-seeking behaviors, a discovery that provides a framework for assessing the underlying circuits. METHODS: Employing TRAP2 (targeted recombination in active populations) male and female mice, in which neurons activated within a defined time frame are permanently tagged, we compared ELA- and control-reared mice, assessing the quantity and distribution of ELA-related neuronal activation. After validating the TRAP2 results using native c-Fos labeling, we defined the molecular identity of this population of activated neurons. RESULTS: We uniquely demonstrated that the TRAP2 system is feasible and efficacious in neonatal mice. Surprisingly, the paraventricular nucleus of the thalamus was robustly and almost exclusively activated by ELA and was the only region distinguishing ELA from typical rearing. Remarkably, a large proportion of ELA-activated paraventricular nucleus of the thalamus neurons expressed CRF(1), the receptor for the stress-related peptide, corticotropin-releasing hormone, but these neurons did not express corticotropin-releasing hormone itself. CONCLUSIONS: The paraventricular nucleus of the thalamus, an important component of reward circuits that is known to encode remote, emotionally salient experiences to influence future motivated behaviors, encodes adverse experiences as remote as those occurring during the early postnatal period and is thus poised to contribute to the enduring deficits in reward-related behaviors consequent to ELA. |
format | Online Article Text |
id | pubmed-10593902 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-105939022023-10-25 Genetic Tagging Uncovers a Robust, Selective Activation of the Thalamic Paraventricular Nucleus by Adverse Experiences Early in Life Kooiker, Cassandra L. Chen, Yuncai Birnie, Matthew T. Baram, Tallie Z. Biol Psychiatry Glob Open Sci Archival Report BACKGROUND: Early-life adversity (ELA) is associated with increased risk for mood disorders, including depression and substance use disorders. These disorders are characterized by impaired reward-related behaviors, suggesting compromised operations of reward-related brain circuits. However, the brain regions engaged by ELA that mediate these enduring consequences of ELA remain largely unknown. In an animal model of ELA, we identified aberrant reward-seeking behaviors, a discovery that provides a framework for assessing the underlying circuits. METHODS: Employing TRAP2 (targeted recombination in active populations) male and female mice, in which neurons activated within a defined time frame are permanently tagged, we compared ELA- and control-reared mice, assessing the quantity and distribution of ELA-related neuronal activation. After validating the TRAP2 results using native c-Fos labeling, we defined the molecular identity of this population of activated neurons. RESULTS: We uniquely demonstrated that the TRAP2 system is feasible and efficacious in neonatal mice. Surprisingly, the paraventricular nucleus of the thalamus was robustly and almost exclusively activated by ELA and was the only region distinguishing ELA from typical rearing. Remarkably, a large proportion of ELA-activated paraventricular nucleus of the thalamus neurons expressed CRF(1), the receptor for the stress-related peptide, corticotropin-releasing hormone, but these neurons did not express corticotropin-releasing hormone itself. CONCLUSIONS: The paraventricular nucleus of the thalamus, an important component of reward circuits that is known to encode remote, emotionally salient experiences to influence future motivated behaviors, encodes adverse experiences as remote as those occurring during the early postnatal period and is thus poised to contribute to the enduring deficits in reward-related behaviors consequent to ELA. Elsevier 2023-01-24 /pmc/articles/PMC10593902/ /pubmed/37881549 http://dx.doi.org/10.1016/j.bpsgos.2023.01.002 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Archival Report Kooiker, Cassandra L. Chen, Yuncai Birnie, Matthew T. Baram, Tallie Z. Genetic Tagging Uncovers a Robust, Selective Activation of the Thalamic Paraventricular Nucleus by Adverse Experiences Early in Life |
title | Genetic Tagging Uncovers a Robust, Selective Activation of the Thalamic Paraventricular Nucleus by Adverse Experiences Early in Life |
title_full | Genetic Tagging Uncovers a Robust, Selective Activation of the Thalamic Paraventricular Nucleus by Adverse Experiences Early in Life |
title_fullStr | Genetic Tagging Uncovers a Robust, Selective Activation of the Thalamic Paraventricular Nucleus by Adverse Experiences Early in Life |
title_full_unstemmed | Genetic Tagging Uncovers a Robust, Selective Activation of the Thalamic Paraventricular Nucleus by Adverse Experiences Early in Life |
title_short | Genetic Tagging Uncovers a Robust, Selective Activation of the Thalamic Paraventricular Nucleus by Adverse Experiences Early in Life |
title_sort | genetic tagging uncovers a robust, selective activation of the thalamic paraventricular nucleus by adverse experiences early in life |
topic | Archival Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593902/ https://www.ncbi.nlm.nih.gov/pubmed/37881549 http://dx.doi.org/10.1016/j.bpsgos.2023.01.002 |
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