Deletion of CRH From GABAergic Forebrain Neurons Promotes Stress Resilience and Dampens Stress-Induced Changes in Neuronal Activity
Dysregulation of the corticotropin-releasing hormone (CRH) system has been implicated in stress-related psychopathologies such as depression and anxiety. Although most studies have linked CRH/CRH receptor 1 signaling to aversive, stress-like behavior, recent work has revealed a crucial role for dist...
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| Format: | Article |
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Frontiers Media S.A.
2019-09-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2019.00986/full |
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| author | Nina Dedic Nina Dedic Claudia Kühne Karina S. Gomes Karina S. Gomes Jakob Hartmann Jakob Hartmann Kerry J. Ressler Mathias V. Schmidt Jan M. Deussing |
| author_facet | Nina Dedic Nina Dedic Claudia Kühne Karina S. Gomes Karina S. Gomes Jakob Hartmann Jakob Hartmann Kerry J. Ressler Mathias V. Schmidt Jan M. Deussing |
| author_sort | Nina Dedic |
| collection | DOAJ |
| description | Dysregulation of the corticotropin-releasing hormone (CRH) system has been implicated in stress-related psychopathologies such as depression and anxiety. Although most studies have linked CRH/CRH receptor 1 signaling to aversive, stress-like behavior, recent work has revealed a crucial role for distinct CRH circuits in maintaining positive emotional valence and appetitive responses under baseline conditions. Here we addressed whether deletion of CRH, specifically from GABAergic forebrain neurons (CrhCKO–GABA mice) differentially affects general behavior under baseline and chronic stress conditions. Expression mapping in CrhCKO–GABA mice revealed absence of Crh in GABAergic neurons of the cortex and limbic regions including the hippocampus, central nucleus of the amygdala and the bed nucleus of the stria terminals, but not in the paraventricular nucleus of hypothalamus. Consequently, conditional CRH knockout animals exhibited no alterations in circadian and stress-induced corticosterone release compared to controls. Under baseline conditions, absence of Crh from forebrain GABAergic neurons resulted in social interaction deficits but had no effect on other behavioral measures including locomotion, anxiety, immobility in the forced swim test, acoustic startle response and fear conditioning. Interestingly, following exposure to chronic social defeat stress, CrhCKO–GABA mice displayed a resilient phenotype, which was accompanied by a dampened, stress-induced expression of immediate early genes c-fos and zif268 in several brain regions. Collectively our data reveals the requirement of GABAergic CRH circuits in maintaining appropriate social behavior in naïve animals and further supports the ability of CRH to promote divergent behavioral states under baseline and severe stress conditions. |
| first_indexed | 2024-12-23T05:11:56Z |
| format | Article |
| id | doaj.art-d997b72259724e658687c6540d4c1c3c |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-23T05:11:56Z |
| publishDate | 2019-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-d997b72259724e658687c6540d4c1c3c2022-12-21T17:58:57ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2019-09-011310.3389/fnins.2019.00986473278Deletion of CRH From GABAergic Forebrain Neurons Promotes Stress Resilience and Dampens Stress-Induced Changes in Neuronal ActivityNina Dedic0Nina Dedic1Claudia Kühne2Karina S. Gomes3Karina S. Gomes4Jakob Hartmann5Jakob Hartmann6Kerry J. Ressler7Mathias V. Schmidt8Jan M. Deussing9Molecular Neurogenetics, Max Planck Institute of Psychiatry, Munich, GermanyDepartment of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, MA, United StatesMolecular Neurogenetics, Max Planck Institute of Psychiatry, Munich, GermanyMolecular Neurogenetics, Max Planck Institute of Psychiatry, Munich, GermanyLaboratory of Neuropsychopharmacology, Paulista State University, Araraquara, BrazilDepartment of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, MA, United StatesStress Resilience, Max Planck Institute of Psychiatry, Munich, GermanyDepartment of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, MA, United StatesStress Resilience, Max Planck Institute of Psychiatry, Munich, GermanyMolecular Neurogenetics, Max Planck Institute of Psychiatry, Munich, GermanyDysregulation of the corticotropin-releasing hormone (CRH) system has been implicated in stress-related psychopathologies such as depression and anxiety. Although most studies have linked CRH/CRH receptor 1 signaling to aversive, stress-like behavior, recent work has revealed a crucial role for distinct CRH circuits in maintaining positive emotional valence and appetitive responses under baseline conditions. Here we addressed whether deletion of CRH, specifically from GABAergic forebrain neurons (CrhCKO–GABA mice) differentially affects general behavior under baseline and chronic stress conditions. Expression mapping in CrhCKO–GABA mice revealed absence of Crh in GABAergic neurons of the cortex and limbic regions including the hippocampus, central nucleus of the amygdala and the bed nucleus of the stria terminals, but not in the paraventricular nucleus of hypothalamus. Consequently, conditional CRH knockout animals exhibited no alterations in circadian and stress-induced corticosterone release compared to controls. Under baseline conditions, absence of Crh from forebrain GABAergic neurons resulted in social interaction deficits but had no effect on other behavioral measures including locomotion, anxiety, immobility in the forced swim test, acoustic startle response and fear conditioning. Interestingly, following exposure to chronic social defeat stress, CrhCKO–GABA mice displayed a resilient phenotype, which was accompanied by a dampened, stress-induced expression of immediate early genes c-fos and zif268 in several brain regions. Collectively our data reveals the requirement of GABAergic CRH circuits in maintaining appropriate social behavior in naïve animals and further supports the ability of CRH to promote divergent behavioral states under baseline and severe stress conditions.https://www.frontiersin.org/article/10.3389/fnins.2019.00986/fullcorticotropin-releasing hormone (CRH)stressanxietyresilienceGABAergic circuitscorticosterone |
| spellingShingle | Nina Dedic Nina Dedic Claudia Kühne Karina S. Gomes Karina S. Gomes Jakob Hartmann Jakob Hartmann Kerry J. Ressler Mathias V. Schmidt Jan M. Deussing Deletion of CRH From GABAergic Forebrain Neurons Promotes Stress Resilience and Dampens Stress-Induced Changes in Neuronal Activity Frontiers in Neuroscience corticotropin-releasing hormone (CRH) stress anxiety resilience GABAergic circuits corticosterone |
| title | Deletion of CRH From GABAergic Forebrain Neurons Promotes Stress Resilience and Dampens Stress-Induced Changes in Neuronal Activity |
| title_full | Deletion of CRH From GABAergic Forebrain Neurons Promotes Stress Resilience and Dampens Stress-Induced Changes in Neuronal Activity |
| title_fullStr | Deletion of CRH From GABAergic Forebrain Neurons Promotes Stress Resilience and Dampens Stress-Induced Changes in Neuronal Activity |
| title_full_unstemmed | Deletion of CRH From GABAergic Forebrain Neurons Promotes Stress Resilience and Dampens Stress-Induced Changes in Neuronal Activity |
| title_short | Deletion of CRH From GABAergic Forebrain Neurons Promotes Stress Resilience and Dampens Stress-Induced Changes in Neuronal Activity |
| title_sort | deletion of crh from gabaergic forebrain neurons promotes stress resilience and dampens stress induced changes in neuronal activity |
| topic | corticotropin-releasing hormone (CRH) stress anxiety resilience GABAergic circuits corticosterone |
| url | https://www.frontiersin.org/article/10.3389/fnins.2019.00986/full |
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