# Decreased Oxytocin Mediates PVN–CA2 and PVN–PrL in Sleep Deprivation-Induced Social Memory Deficits

## TL;DR

This study shows how sleep deprivation impairs social memory by reducing oxytocin in specific brain pathways, and how stimulating these pathways can restore memory function.

## Contribution

The study identifies specific brain pathways (PVNOXT–CA2 and PVNOXT–PrL) and their causal roles in sleep deprivation-induced social memory deficits.

## Key findings

- Chronic sleep deprivation reduces oxytocin release in the hippocampal CA2 and PrL, impairing social memory.
- Optogenetic activation of PVNOXT neurons can transiently or sustainably restore social memory deficits caused by sleep deprivation.
- PVNOXT–CA2 and PVNOXT–PrL pathways have distinct roles in encoding and retrieval of social memory.

## Abstract

While sleep disorders are a known correlate of social memory deficits, the underlying neurocircuitry and molecular mechanisms remain poorly understood. Using an oxytocin (OXT)-specific sensor imaging approach, we discovered that chronic sleep deprivation (SD) reduced OXT neuropeptide release in the hippocampal CA2 and prelimbic cortex (PrL), thereby disrupting social memory encoding and retrieval processes, respectively. Using fiber photometry recordings and in vitro electrophysiology, we identified the activity of the predominantly OXT-expressing neurons in the paraventricular hypothalamic nucleus (PVNOXT) were reduced following SD. Specific optogenetic activation of the PVNOXT–CA2 pathway during encoding phase or PVNOXT–PrL pathway during retrieval transiently restored SD-induced social memory deficits. Conversely, optogenetic high-frequency activation of PVNOXT neurons enhanced the function of both PVNOXT–CA2 and PVNOXT–PrL pathways, promoting increased OXT release and providing sustained protection against SD-induced social memory deficits. These findings offer causal evidence that the PVNOXT–CA2 and PVNOXT–PrL pathways exert distinct modulatory roles in sleep-related social memory deficits and thereby nominate these pathways as precise targets for neuromodulation in sleep-related cognitive disorders.