Silencing of pyramidal neurons in the anterior piriform cortex mediates olfactory dysfunction and social novelty deficits in mice.

BACKGROUND: The olfactory system plays a critical role in modulating social cognition, with the anterior piriform cortex (aPC) serving as a key hub. However, the specific contribution of aPC pyramidal neurons to social regulation remains poorly understood. METHODS: In this study, we selectively silenced these neurons in C57BL/6J mice using a genetic apoptosis approach. TUNEL staining confirmed the specific loss of targeted neurons in the experimental group. The buried food test and the Go/No-Go odor discrimination assay were used to verify the effects of aPC pyramidal neuron apoptosis on the olfactory ability of mice. The three-chamber social test was used to assess the sociability and social novelty recognition ability of mice. The open field test was used to assess the locomotor ability and anxiety level of mice. RESULTS: Buried food and Go/No-Go odor discrimination assays revealed deficits in both olfactory sensitivity and complex odor discrimination. Results from three-chamber tests indicated that while basic sociability remained intact, social novelty recognition was significantly impaired. Notably, no impairments in anxiety or motor function were observed. CONCLUSIONS: These findings demonstrate that aPC pyramidal neurons are essential for mediating olfactory discrimination and social novelty recognition, identifying them as a core node within the olfactory-social cognition circuit and a potential therapeutic target for interventions addressing social cognitive impairments.