Molecular and Cellular Adaptations in Hippocampal Parvalbumin Neurons Mediate Behavioral Responses to Chronic Social Stress.

Autor:	Bhatti DL; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, United States.; Program in Neuroscience, Harvard Medical School, Boston, MA, United States., Medrihan L; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, United States., Chen MX; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, United States., Jin J; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, United States., McCabe KA; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, United States., Wang W; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, United States.; Bioinformatics Resource Center, The Rockefeller University, New York, NY, United States., Azevedo EP; Laboratory of Molecular Genetics, The Rockefeller University, New York, NY, United States., Ledo JH; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, United States., Kim Y; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, United States.; Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, United States.; Brain Health Institute, Rutgers University, Piscataway, NJ, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular neuroscience [Front Mol Neurosci] 2022 Jun 24; Vol. 15, pp. 898851. Date of Electronic Publication: 2022 Jun 24 (Print Publication: 2022).
DOI:	10.3389/fnmol.2022.898851
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Bhatti, Medrihan, Chen, Jin, McCabe, Wang, Azevedo, Ledo and Kim.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu