A ventral hippocampal-lateral septum pathway regulates social novelty preference

The ability to distinguish strangers from familiar individuals is crucial for the survival of most mammalian species. In humans, an inability to recognize kin and familiar individuals and engage in appropriate behaviors is associated with several types of dementia, including Alzheimer's disease. Mice preferentially spend more time investigating a novel individual relative to a familiar individual. Yet, how social novelty-related information drives increased investigation of the novel animal remains poorly understood. Recent evidence has implicated the ventral hippocampus (vHPC) as a key node in encoding information about conspecific identity. Of particular interest are vHPC projections to the lateral septum (LS), a region that has been implicated in driving a wide range of motivated social behaviors. In this study using chemogenetics, optogenetics, and monosynaptic rabies tracing, we identified a novel vHPC-LS-ventral tegmental area (VTA) pathway that is necessary for mice to preferentially investigate novel conspecifics. Using monosynaptic rabies tracing, we established that LS neurons make direct monosynaptic connections onto dopaminergic neurons in the VTA. Thus, we have identified a potential pathway via which conspecific identity could be transformed to drive motivated social behaviors.