Oxytocin specifically participates in social memory encoding by exciting stellate neurons in the lateral entorhinal...

Oxytocin (OXT) has emerged as a key neuromodulator of social cognition, yet the precise neural circuits underlying its role in social memory remain poorly defined. In this study, we identify a specific mechanism by which OXT regulates social memory encoding through the lateral entorhinal cortex (LEC), a critical gateway to the hippocampus.

Using whole-cell patch-clamp recordings in mouse brain slices, we examined the effects of OXT on stellate neurons in the superficial layers of the LEC. Behavioral analyses were performed to determine the role of intra-LEC OXT signaling in the encoding and retrieval of social memory. Pharmacological blockade of OXTRs in the LEC was used to assess its effects on social recognition memory and spatial memory performance.

OXT excited stellate neurons in the superficial layers of the LEC via activation of oxytocin receptors (OXTRs). This excitation was mediated by membrane depolarization and enhanced excitatory synaptic transmission, as evidenced by an increased amplitude of miniature excitatory postsynaptic currents. Intra-LEC OXT signaling was essential for the encoding, but not the retrieval, of social memory. Pharmacological blockade of OXTRs in the LEC selectively impaired social recognition memory without affecting spatial memory performance. Furthermore, inhibition of OXTRs during the recall phase did not disrupt memory expression, indicating a specific role in memory formation.

These findings establish the LEC as a critical node for OXT-dependent modulation of social memory and suggest that OXT enhances the flow of social information to the hippocampus via direct excitation of LEC stellate neurons. This circuit-specific action provides a mechanistic basis for the selective influence of OXT on social cognition and highlights the LEC-hippocampal pathway as a potential target for therapeutic intervention in social memory deficits associated with neuropsychiatric disorders.