Medial septum glutamate neurons are essential for spatial goal-directed memory

The medial septum (MS), a brain region containing acetylcholine, GABA and glutamate neurons, is essential for learning and memory. However, whether MS glutamate neurons contribute to memory is unknown. Here, we use calcium imaging and optogenetic silencing to determine the function of MS glutamate neurons in mice performing a spatial allocentric memory navigation task. While MS glutamate neurons appeared randomly active during free exploration, two groups of glutamate neurons emerged during training in a five-arm star maze, distinguished by their peak activity. The largest group was predominantly activated before locomotion whereas the other was primarily active when mice reached the reward site. Both populations were preferentially activated for correct over incorrect trajectories. Interestingly, optogenetic silencing of MS glutamate neurons immediately before mice start navigating, induced significant spatial memory impairments. Together these results demonstrate that MS glutamate neurons heterogeneously encode navigationally relevant information and are essential for spatial learning.