Two septal-entorhinal GABAergic projections differentially control coding properties of spatially tuned neurons in...

Septal parvalbumin-expressing (PV⁺) and calbindin-expressing (CB⁺) projections inhibit low-threshold and fast-spiking interneurons, respectively, in the medial entorhinal cortex (MEC). We investigate how the two inputs control neuronal activity in the MEC in freely moving mice. Stimulation of PV⁺ and CB⁺ terminals causes disinhibition of spatially tuned MEC neurons, but exerts differential effects on temporal coding and burst firing. Thus, recruitment of PV⁺ projections disrupts theta-rhythmic firing of MEC neurons, while stimulation of CB⁺ projections increases burst firing of grid cells and enhances phase precession in a cell-type-specific manner. Inactivation of septal PV⁺ or CB⁺ neurons differentially affects context, reference, and working memory. Together, our results reveal how specific connectivity of septal GABAergic projections with MEC interneurons translates into differential modulation of MEC neuronal coding.