Neural circuit mechanisms explain how chronic sleep loss disrupts social memory

Social memory - the ability to recognize familiar individuals and distinguish them from strangers - is fundamental to social cognition. Deficits in social memory are hallmarks of multiple neuropsychiatric and neurodegenerative disorders, including autism spectrum disorder (ASD), post-traumatic stress disorder (PTSD), and Alzheimer's disease (AD). Notably, these conditions frequently co-occur with chronic sleep disturbances. Although extensive evidence linking sleep disruption to impaired social cognition, the underlying circuit-level and neurochemical mechanisms have remained largely unresolved.

To address these challenges, the research team led by Prof. Haibo Xu and Prof. Linlin Bi at Wuhan University employed a combination of high-resolution oxytocin (OXT) sensor imaging, optogenetics, calcium imaging, and electrophysiological approaches to uncover the neural circuit mechanisms underlying sleep disruption-induced social memory impairment, as well as potential intervention strategies.

The study found that chronic sleep disruption persistently impairs social memory;OXT release is differentially encoded in hippocampal CA2 during social novelty encoding, and prelimbic cortex (PrL) during retrieval of familiar individuals; PVNOXT-CA2 and PVNOXT-PrL - respectively govern social memory encoding and retrieval;High-frequency (100 Hz) stimulation of PVNOXT neurons restores neuronal excitability, enhances OXT release, and produces sustained behavioral recovery.

This work provides causal evidence linking sleep disruption, oxytocin signaling, and social memory circuits. Importantly, it highlights restoration of the oxytocin neuronal source as a more effective strategy than downstream circuit modulation alone. The findings offer a conceptual and experimental framework for developing neuromodulation-based therapies, optimizing oxytocin-related interventions, and advancing precision medicine approaches for social cognitive dysfunction associated with sleep disorders.