Mapping the physiological and molecular markers of stress and SSRI antidepressant treatment in S100a10 corticostriatal neurons.

TitleMapping the physiological and molecular markers of stress and SSRI antidepressant treatment in S100a10 corticostriatal neurons.
Publication TypeJournal Article
Year of Publication2019
AuthorsSargin, D, Chottekalapanda, RU, Perit, KE, Yao, V, Chu, D, Sparks, DW, Kalik, S, Power, SK, Troyanskaya, OG, Schmidt, EF, Greengard, P, Lambe, EK
JournalMol Psychiatry
Date Published2019 Aug 20
ISSN1476-5578
Abstract

In mood disorders, psychomotor and sensory abnormalities are prevalent, disabling, and intertwined with emotional and cognitive symptoms. Corticostriatal neurons in motor and somatosensory cortex are implicated in these symptoms, yet mechanisms of their vulnerability are unknown. Here, we demonstrate that S100a10 corticostriatal neurons exhibit distinct serotonin responses and have increased excitability, compared with S100a10-negative neurons. We reveal that prolonged social isolation disrupts the specific serotonin response which gets restored by chronic antidepressant treatment. We identify cell-type-specific transcriptional signatures in S100a10 neurons that contribute to serotonin responses and strongly associate with psychomotor and somatosensory function. Our studies provide a strong framework to understand the pathogenesis and create new avenues for the treatment of mood disorders.

DOI10.1038/s41380-019-0473-6
Alternate JournalMol. Psychiatry
PubMed ID31431686
Grant ListNARSAD Young Investigator Award / / Brain and Behavior Research Foundation (Brain & Behavior Research Foundation) /
Postdoctoral Fellowship / / Alzheimer Society (Société Alzheimer) /
MH090963 / / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) /
R01NS091722 / / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) /
P30 Center DA035756 / / U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) /
T32 HG003284 / HG / NHGRI NIH HHS / United States