Social Instability in Adolescent Mice Leads to Lasting Cognitive Deficits with Reduction of Intra-Hippocampal Functional Connectivity and Parvalbumin-Containing Interneurons with Perineuronal Nets.

Background Adolescent social stress can be detrimental to developing hippocampal-prefrontal circuits and is associated with adverse cognitive outcomes. We previously found that adolescent social instability stress (SIS) in mice resulted in later-life memory retrieval impairment as measured with novel object recognition (NOR). Methods Mice were behaviorally assessed using novel object recognition (NOR), social interaction, and the elevated plus maze. We analyzed local-field potential data during NOR. We assessed the 1/f slope of the power spectral density within the dCA1, dCA3, vCA1, and mPFC and analyzed coherence between the ventral hippocampus and medial prefrontal cortex (mPFC) and dorsal CA3 to CA1 as animals were near objects during NOR. Additionally we measured serum corticosterone levels immediately following the termination of the adolescent SIS manipulation, and used immunohistochemistry to quantify perineuronal nets (PNN) around parvalbumin (PV)-positive neurons using antibodies for PV and Wisteria floribunda agglutinin (WFA), which labels PNNs. Results NOR deficits in SIS mice were replicated. No significant changes to social interactions, elevated plus maze or the aperiodic component of spectral parameterization were observed. Intra-hippocampal gamma coherence was reduced in SIS animals around the novel object relative to controls. PNN density was reduced in the mPFC of stressed animals. Corticosterone was lower in SIS mice relative to controls. Conclusions Data support the hypothesis that altered social interactions during adolescence can result in structural, electrophysiological, and cognitive deficits that persist well into adulthood.