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  • Oxytocin neurons mediate the effect of social isolation via the VTA circuits.

Oxytocin neurons mediate the effect of social isolation via the VTA circuits.

eLife (2022-04-23)
Stefano Musardo, Alessandro Contestabile, Marit Knoop, Olivier Baud, Camilla Bellone
ABSTRACT

Social interaction during adolescence strongly influences brain function and behavior, and the recent pandemic has emphasized the devastating effect of social distancing on mental health. While accumulating evidence has shown the importance of the reward system in encoding specific aspects of social interaction, the consequences of social isolation on the reward system and the development of social skills later in adulthood are still largely unknown. Here, we found that 1 week of social isolation during adolescence in male mice increased social interaction at the expense of social habituation and social novelty preference. Behavioral changes were accompanied by the acute hyperexcitability of putative dopamine (pDA) neurons in the ventral tegmental area and long-lasting expression of GluA2-lacking AMPARs at excitatory inputs onto pDA neurons that project to the prefrontal cortex. Social isolation-dependent behavioral deficits and changes in neural activity and synaptic plasticity were reversed by chemogenetic inhibition of oxytocin neurons in the paraventricular nucleus of the hypothalamus. These results demonstrate that social isolation in male mice has acute and long-lasting effects on social interaction and suggest that homeostatic adaptations mediate these effects within the reward circuit.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Tyrosine Hydroxylase Antibody, clone LNC1, ascites fluid, clone LNC1, Chemicon®
Sigma-Aldrich
Anti-Oxytocin Antibody, serum, Chemicon®
Sigma-Aldrich
HEPES, ≥99.5% (titration)
Sigma-Aldrich
Anti-Neurophysin 2/NP-AVP Antibody, clone PS 45, clone PS 45, from mouse
Sigma-Aldrich
Choline chloride, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥98%