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.
Highlights
These authors contributed : Derya Sargin, Revathy U
To decipher the unique physiological characteristics of S100a10 neurons, we performed whole-cell patch-clamp electrophysiology in cortical slices obtained from S100a10 bacTRAP mice
We focused on motor and somatosensory cortical areas which are critical for psychomotor and sensory functions and harbor an abundant expression of S100a10 in layer 5a corticostriatal neurons [12] (Fig. 1a, b)
Summary
We characterized the transcriptional alterations that mediate changes in behavior and physiology across healthy, stressed, and chronic antidepressant treatment states by profiling the translatome of motor and somatosensory S100a10 neurons using translating ribosome affinity purification (TRAP) analysis. Together, these studies provide a strong molecular framework for defining the complex physiology of a selective population of sensory and motor cortical neurons that, when perturbed, leads to mood dysfunction and may identify new avenues for treatment of sensory and motor symptoms
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