Lateral Septal Circuits Govern Schizophrenia-Like Effects of Ketamine on Social Behavior
bioRxiv Preprint Server August 8, 2023 Ruixiang Wang, Zeru Peterson, Nagalakshmi Balasubramanian et al. 1 citation preprint
Social deficits in schizophrenia may stem from underactivity in a specific brain region called the lateral septum (LS). In mice given chronic ketamine to model schizophrenia-like symptoms, the LS showed reduced activation during social encounters. Artificially stimulating the LS restored normal social behavior, while silencing it in healthy mice caused social impairments. Genetic analysis of LS neurons revealed dysregulation of genes linked to neuronal excitability and cell death, with 38 genes overlapping those implicated in human schizophrenia. Activating LS neurons triggered activity in brain areas involved in reward, fear, and sensory processing. The findings suggest the LS acts as a central hub for social behavior, and its dysfunction may underlie social challenges in schizophrenia, pointing to potential targets for new therapies.