Abstract
Social memory, the ability to recall and comprehend social interactions, depends on hippocampal circuits, particularly the dorsal CA2. Disruptions in inhibitory transmission within CA2 have been implicated in neuropsychiatric and neurodevelopmental disorders, including schizophrenia and autism spectrum disorder. However, the extrahippocampal mechanisms regulating CA2-dependent social memory remain poorly understood. The medial septum (MS), a major source of hippocampal afferents involved in network synchronization and information processing, has emerged as a potential modulator of social memory. Nevertheless, the contribution of MS GABAergic neurons to social memory remains unclear. Here, we selectively depleted MS GABAergic neurons using an anti-vesicular GABA transporter-saporin immunotoxin (anti-vGAT-SAP) and examined the resulting behavioral consequences. We found that loss of MS GABAergic neurons selectively impaired social memory, whereas sociability, social novelty preference and novel object recognition remain intact. In addition, lesioned animals exhibited impaired spatial memory together with increased locomotion, exploratory activity, and possible anxiolytic-like effects. These findings identify MS GABAergic neurons as a critical component of the neural circuitry underlying social memory and suggest that dysfunction of septal inhibitory signaling may contribute to the social and cognitive deficits associated with neuropsychiatric and neurological conditions.