Two septal-entorhinal GABAergic projections differentially control coding properties of spatially tuned neurons in the medial entorhinal cortex

Abstract

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.

Keywords: MEC, septum; burst firing; disinhibition; grid cells; interneurons; medial entorhinal cortex; phase coding; phase precession; theta rhythm.