Molecular and Cellular Adaptations in Hippocampal Parvalbumin Neurons Mediate Behavioral Responses to Chronic Social Stress
Parvalbumin-expressing interneurons (PV neurons) maintain inhibitory control of local circuits implicated in behavioral responses to environmental stressors. However, the roles of molecular and cellular adaptations in PV neurons in stress susceptibility or resilience have not been clearly establishe...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.898851/full |
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| author | Dionnet L. Bhatti Dionnet L. Bhatti Lucian Medrihan Michelle X. Chen Junghee Jin Kathryn A. McCabe Wei Wang Wei Wang Estefania P. Azevedo Jose H. Ledo Yong Kim Yong Kim Yong Kim |
| author_facet | Dionnet L. Bhatti Dionnet L. Bhatti Lucian Medrihan Michelle X. Chen Junghee Jin Kathryn A. McCabe Wei Wang Wei Wang Estefania P. Azevedo Jose H. Ledo Yong Kim Yong Kim Yong Kim |
| author_sort | Dionnet L. Bhatti |
| collection | DOAJ |
| description | Parvalbumin-expressing interneurons (PV neurons) maintain inhibitory control of local circuits implicated in behavioral responses to environmental stressors. However, the roles of molecular and cellular adaptations in PV neurons in stress susceptibility or resilience have not been clearly established. Here, we show behavioral outcomes of chronic social defeat stress (CSDS) are mediated by differential neuronal activity and gene expression in hippocampal PV neurons in mice. Using in vivo electrophysiology and chemogenetics, we find increased PV neuronal activity in the ventral dentate gyrus is required and sufficient for behavioral susceptibility to CSDS. PV neuron-selective translational profiling indicates mitochondrial oxidative phosphorylation is the most significantly altered pathway in stress-susceptible versus resilient mice. Among differentially expressed genes associated with stress-susceptibility and resilience, we find Ahnak, an endogenous regulator of L-type calcium channels which are implicated in the regulation of mitochondrial function and gene expression. Notably, Ahnak deletion in PV neurons impedes behavioral susceptibility to CSDS. Altogether, these findings indicate behavioral effects of chronic stress can be controlled by selective modulation of PV neuronal activity or a regulator of L-type calcium signaling in PV neurons. |
| first_indexed | 2024-12-12T06:26:11Z |
| format | Article |
| id | doaj.art-27969e908edb4910a5252d8e0f84e00f |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-12T06:26:11Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-27969e908edb4910a5252d8e0f84e00f2022-12-22T00:34:44ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-06-011510.3389/fnmol.2022.898851898851Molecular and Cellular Adaptations in Hippocampal Parvalbumin Neurons Mediate Behavioral Responses to Chronic Social StressDionnet L. Bhatti0Dionnet L. Bhatti1Lucian Medrihan2Michelle X. Chen3Junghee Jin4Kathryn A. McCabe5Wei Wang6Wei Wang7Estefania P. Azevedo8Jose H. Ledo9Yong Kim10Yong Kim11Yong Kim12Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, United StatesProgram in Neuroscience, Harvard Medical School, Boston, MA, United StatesLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, United StatesLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, United StatesLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, United StatesLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, United StatesLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, United StatesBioinformatics Resource Center, The Rockefeller University, New York, NY, United StatesLaboratory of Molecular Genetics, The Rockefeller University, New York, NY, United StatesLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, United StatesLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, United StatesDepartment of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, United StatesBrain Health Institute, Rutgers University, Piscataway, NJ, United StatesParvalbumin-expressing interneurons (PV neurons) maintain inhibitory control of local circuits implicated in behavioral responses to environmental stressors. However, the roles of molecular and cellular adaptations in PV neurons in stress susceptibility or resilience have not been clearly established. Here, we show behavioral outcomes of chronic social defeat stress (CSDS) are mediated by differential neuronal activity and gene expression in hippocampal PV neurons in mice. Using in vivo electrophysiology and chemogenetics, we find increased PV neuronal activity in the ventral dentate gyrus is required and sufficient for behavioral susceptibility to CSDS. PV neuron-selective translational profiling indicates mitochondrial oxidative phosphorylation is the most significantly altered pathway in stress-susceptible versus resilient mice. Among differentially expressed genes associated with stress-susceptibility and resilience, we find Ahnak, an endogenous regulator of L-type calcium channels which are implicated in the regulation of mitochondrial function and gene expression. Notably, Ahnak deletion in PV neurons impedes behavioral susceptibility to CSDS. Altogether, these findings indicate behavioral effects of chronic stress can be controlled by selective modulation of PV neuronal activity or a regulator of L-type calcium signaling in PV neurons.https://www.frontiersin.org/articles/10.3389/fnmol.2022.898851/fullchronic stresssusceptibilityresiliencedentate gyrusparvalbumin interneuronsAhnak |
| spellingShingle | Dionnet L. Bhatti Dionnet L. Bhatti Lucian Medrihan Michelle X. Chen Junghee Jin Kathryn A. McCabe Wei Wang Wei Wang Estefania P. Azevedo Jose H. Ledo Yong Kim Yong Kim Yong Kim Molecular and Cellular Adaptations in Hippocampal Parvalbumin Neurons Mediate Behavioral Responses to Chronic Social Stress Frontiers in Molecular Neuroscience chronic stress susceptibility resilience dentate gyrus parvalbumin interneurons Ahnak |
| title | Molecular and Cellular Adaptations in Hippocampal Parvalbumin Neurons Mediate Behavioral Responses to Chronic Social Stress |
| title_full | Molecular and Cellular Adaptations in Hippocampal Parvalbumin Neurons Mediate Behavioral Responses to Chronic Social Stress |
| title_fullStr | Molecular and Cellular Adaptations in Hippocampal Parvalbumin Neurons Mediate Behavioral Responses to Chronic Social Stress |
| title_full_unstemmed | Molecular and Cellular Adaptations in Hippocampal Parvalbumin Neurons Mediate Behavioral Responses to Chronic Social Stress |
| title_short | Molecular and Cellular Adaptations in Hippocampal Parvalbumin Neurons Mediate Behavioral Responses to Chronic Social Stress |
| title_sort | molecular and cellular adaptations in hippocampal parvalbumin neurons mediate behavioral responses to chronic social stress |
| topic | chronic stress susceptibility resilience dentate gyrus parvalbumin interneurons Ahnak |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.898851/full |
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