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

Mol Psychiatry. 2020 May;25(5):1112-1129. doi: 10.1038/s41380-019-0473-6. Epub 2019 Aug 20.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A2 / metabolism*
  • Antidepressive Agents / pharmacology*
  • Biomarkers / metabolism
  • Male
  • Mice
  • Motor Cortex / pathology
  • Neurons / drug effects*
  • Neurons / metabolism*
  • S100 Proteins / metabolism*
  • Serotonin / metabolism
  • Serotonin Uptake Inhibitors / pharmacology*
  • Somatosensory Cortex / pathology
  • Stress, Psychological / metabolism*
  • Stress, Psychological / physiopathology

Substances

  • Annexin A2
  • Antidepressive Agents
  • Biomarkers
  • S100 Proteins
  • S100 calcium binding protein A10
  • Serotonin Uptake Inhibitors
  • Serotonin