Medial septal cholinergic neurotransmission is essential for social memory in mice

Social memory, a fundamental component of social behavior, is essential for the recognition and recall of familiar and novel animals/humans which is disrupted in several neuropsychiatric disorders. Although hippocampal circuitry is crucial for social memory, the role of extra-hippocampal regions in this behavior remains elusive. Here, we identified the physiological link between medial septal dependent cholinergic theta oscillations in the hippocampus and social memory behavior. We found that selective ablation of cholinergic neurons in the medial septum impaired social memory in mice, while their sociability and social novelty remained intact. Additionally, these mice showed an attenuation of cholinergic theta oscillations (3-7 Hz) in the hippocampal dorsal CA2 (dCA2) region. Furthermore, enhancing dCA2 theta oscillations by elevating cholinergic signaling using acetylcholinesterase inhibitor rescued social memory deficit. Together, these results indicate that 1) medial septal cholinergic neurons are essential for modulating social memory 2) cholinergic hippocampal theta oscillations contribute to social memory processes.