Parvalbumin interneurons are differentially connected to principal cells in inhibitory feedback microcircuits along the dorso-ventral axis of the medial entorhinal cortex

Abstract

The medial entorhinal cortex (mEC) shows a high degree of spatial tuning, predominantly grid-cell activity, which is reliant on robust, dynamic inhibition provided by local interneurons (INs). In fact, feedback inhibitory microcircuits involving fast-spiking parvalbumin (PV) basket cells (BCs) are believed to contribute dominantly to the emergence of grid-field firing in principal cells (PrCs). However, the strength of PV BC-mediated inhibition onto PrCs is not uniform in this region, but high in the dorsal and weak in the ventral mEC. This is in good correlation with divergent grid field sizes, but the underlying morphological and physiological mechanisms remain unknown. In this study, we examined PV BCs in layer 2/3 of the mEC characterizing their intrinsic physiology, morphology, and synaptic connectivity in the juvenile rat. We show that while intrinsic physiology and morphology are broadly similar over the dorso-ventral axis, PV BCs form more connections onto local PrCs in the dorsal mEC, independent of target cell type. In turn, the major PrC subtypes, pyramidal (PC) and stellate cells (SC), form connections onto PV BCs with lower, but equal probability. These data thus identify inhibitory connectivity as source of the gradient of inhibition, plausibly explaining divergent grid field formation along this dorso-ventral axis of the mEC.

Significance Statement Inhibition by parvalbumin basket cells (PV BCs) is essential for the emergence of grid firing in principal cells (PrCs) in the medial entorhinal cortex (mEC).The strength of PV BC-mediated inhibition decreases along the dorso-ventral axis, in correlation with the grid field size of spatially tuned PrCs. In this study, to identify underlying cellular mechanisms, we combined electrophysiological recordings and neuroanatomical analysis investigating properties and connectivity of PV BCs in layer 2/3 of the rat mEC. While morphological and physiological properties were largely uniform, IN-PrC connectivity was higher in the dorsal than ventral mEC. Thus, our results indentify a difference in PV BC connectivity as source of the inhibitory gradient in the mEC with implications for grid size modulation.