Medial septum glutamatergic neurons support speed coding and grid cell spatial stability in the medial entorhinal cortex

Abstract

Successful navigation requires the integration of self-motion signals with spatial representations, yet the circuits that provide velocity information necessary for stable grid cell firing remain incompletely understood. Here, we identify medial septal (MS) glutamatergic neurons as a critical component of this pathway. Using cell-type-specific optogenetic silencing combined with in vivo electrophysiology in freely moving mice, we show that MS glutamatergic neurons support the fidelity of firing rate-based speed coding in the medial entorhinal cortex (MEC). Silencing this population reduced grid cell spatial periodicity and stability and produced distortions of grid firing fields. Silencing also reduced theta phase-locking strength in strongly theta-modulated MEC neurons. Model simulations of a hybrid oscillatory interference-continuous attractor network with reductions in speed-signal fidelity disrupted grid periodicity and reproduced features of the spatial distortions observed in vivo. Together, these findings identify a septo-entorhinal circuit that coordinates self-motion information with the spatial and temporal organization of MEC activity to maintain a stable neural representation of space.