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.

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