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

• Published in: Molecular psychiatry Vol. 25; no. 5; pp. 1112 - 1129
• Main Authors: Sargin, Derya, Chottekalapanda, Revathy U., Perit, Kristina E., Yao, Victoria, Chu, Duong, Sparks, Daniel W., Kalik, Salina, Power, Saige K., Troyanskaya, Olga G., Schmidt, Eric F., Greengard, Paul, Lambe, Evelyn K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2020; Nature Publishing Group
• Subjects: 45/91; 631/337; 631/378; 631/443; 64/110; 692/699/476/1414; 9/74; 96/95; Animals; Annexin A2 - metabolism; Antidepressants; Antidepressive Agents - pharmacology; Behavioral Sciences; Biological Psychology; Biomarkers - metabolism; Calcium-binding protein; Cognitive ability; Comparative analysis; Cortex (motor); Cortex (somatosensory); Emotional disorders; Excitability; Male; Medicine; Medicine & Public Health; Mice; Mood; Mood disorders; Motor Cortex - pathology; Neurons; Neurons - drug effects; Neurons - metabolism; Neurosciences; Pharmacotherapy; Physiological aspects; Psychiatry; S100 protein; S100 Proteins - metabolism; Serotonin; Serotonin - metabolism; Serotonin uptake inhibitors; Serotonin Uptake Inhibitors - pharmacology; Social interactions; Somatosensory Cortex - pathology; Stress; Stress, Psychological - metabolism; Stress, Psychological - physiopathology; Transcription; Canada
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/s41380-019-0473-6

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.