Short- and long-term effects of chronic social stress on motor cortical neuroplasticity in mice

Anne-Kathrin Gellner1, Aileen Sitter1, Alexandra Philipsen1, Andreas Zimmer2, Valentin Stein3

1 Department of Psychiatry and Psychotherapy, University Hospital Bonn
2 Institute of Molecular Psychiatry, University of Bonn
3 Institute of Physiology 2, University of Bonn

Chronic stress is a major cause of neuropsychiatric conditions such as depression and post-traumatic stress disorder leading to a massive health burden worldwide. In contrast to well-studied affective and cognitive symptoms, motor retardation known to accompany many psychiatric conditions is not well understood yet.

Adult male Thy1-GFP M mice were equipped with a chronic cranial window over M1. The same cortical regions of interest were repeatedly visualized via in vivo 2-photon microscopy before and after 10 days of chronic social defeat stress or control conditions which were followed by motor skill learning. Imaging continued throughout and after the learning phase and for up to 5 weeks after the stress had ended. Several biological samples were collected for marker analysis.

Chronic social stress led to depression-like behavior with anhedonia, reduced sociability and self-care. A subgroup of animals showed signs of resilience. All stressed mice showed differently altered motor learning capabilities depending on their individual vulnerability and was accompanied by a reduced spine density in the motor cortex. Spine dynamics remained altered compared to controls depending on their stress phenotype which also correlated with short- and long-term changes in the HPA-axis.

These data demonstrate severe short- and long-term effects of chronic social stress on the dynamics of motor cortical neuroplasticity and motor learning in a longitudinal in vivo approach. The HPA-axis was chronically altered hinting at a potential mechanism regulating individual stress vulnerability.