Long-term changes of parvalbumin- and somatostatin-positive interneurons of the primary motor cortex after chronic social defeat stress depend on individual stress-vulnerability

Abstract

Chronic stress is a major risk factor for developing mental illnesses and cognitive deficiencies although stress-susceptibility varies individually. In a recent study, we established the connection between chronic social defeat stress (CSDS) and impaired motor learning abilities accompanied by chronically disturbed structural neuroplasticity in the primary motor cortex (M1) of mice. In this study, we further investigated the long-term effects of CSDS exposure on M1, focusing on the interneuronal cell population. We used repeated CSDS to elicit effects across behavioral, endocrinological, and metabolic parameters in mice. Susceptible and resilient phenotypes were discriminated by symptom load and motor learning abilities were assessed on the rotarod. Structural changes in interneuronal circuits of M1 were studied by immunohistochemistry using parvalbumin (PV+) and somatostatin (SST+) markers. Stress-susceptible mice had a blunted stress hormone response and impaired motor learning skills. These mice presented reduced numbers of both interneuron populations in M1 with layer-dependent distribution, while alterations in cell size and immunoreactivity were found in both susceptible and resilient individuals. These results, together with our previous data, suggest that stress-induced cell loss and degeneration of the GABAergic interneuronal network of M1 could underlay impaired motor learning, due to their role in controlling the excitatory output and spine dynamics of principal neurons required for this task. Our study further highlights the importance of long-term outcomes of chronically stressed individuals which are translationally important due to the long timecourses of stress-induced neuropsychiatric disorders.