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 one 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 (VTA) and long-lasting expression of GluA2-lacking AMPARs at excitatory inputs onto pDA neurons that project to the prefrontal cortex (PFC). 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 (PVN) 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.
All data generated or analysed during this study and the statistical results are included in the manuscript and supporting files. Source raw data files have been provided for all the figures and supplement figures: Figures 1 source data, Figures 2 source data, Figures 3 source data, Figures 4 source data, Figures 5 source data, Figures 6 source data, Figure 1-figure supplement 1 source data, Figure 1-figure supplement 2 source data, Figure 1-figure supplement 3 source data, Figure 3-figure supplement 1 source data, Figure 4 -figure supplement 1 source data, Figure 4 -figure supplement 2 source data, Figure 5 -figure supplement 1 source data.
- Camilla Bellone
- Camilla Bellone
- Camilla Bellone
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All the procedures performed at UNIGE complied with the Swiss National Institutional Guidelines on Animal Experimentation and were approved by the Swiss Cantonal Veterinary Office Committees for Animal Experimentation (Licence number GE-168/18).
- Joseph F Cheer, University of Maryland School of Medicine, United States
© 2022, Musardo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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