Parvalbumin Interneurons Are Differentially Connected to Principal Cells in Inhibitory Feedback Microcircuits along the Dorsoventral Axis of the Medial Entorhinal Cortex.

Sabine Grosser,Federico J Barreda,Sam A Booker,Imre Vida,Dietmar Schmitz,Prateep Beed

doi:10.1523/eneuro.0354-20.2020

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 cell 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 morphologic and physiological mechanisms remain unknown. In this study, we examined PV BCs in layer (L)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 dorsoventral 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 cell (PC) and stellate cell (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 dorsoventral axis of the mEC.

Highlights

The hippocampal formation, comprising the entorhinal cortex and hippocampus as its central structures, is a key component of the mammalian spatial navigation system (O’Keefe and Nadel, 1978)
Given that the excitability of a given neuron is directly related to its synaptic input, we asked whether the spontaneous EPSCs arriving onto PV basket cells (BCs) in the dorsal medial entorhinal cortex (mEC) were stronger than those arriving in the ventral mEC (Fig. 1E)
parvalbumin basket cells (PV BCs) from the dorsal mEC had a total dendritic length of 4.8 6 0.3 mm (22 PV BCs from 18 rats), comparable to those in the ventral mEC with 4.4 6 0.3 mm (21 PV BCs from 17 rats; p = 0.29, Mann–Whitney U test; Fig. 2A)

Summary

Introduction

The hippocampal formation, comprising the entorhinal cortex and hippocampus as its central structures, is a key component of the mammalian spatial navigation system (O’Keefe and Nadel, 1978). Spatially modulated neuronal activity has been described in essentially all areas of the formation, most notably as place cells in CA1 (O’Keefe, 1979), grid cells in L2/3 and L5 of the mEC (Sargolini et al, 2006; Boccara et al, 2010) and the dentate gyrus (Park et al, 2011). PrCs of mEC L2/3 comprise reelincontaining stellate cells (SCs), which are the canonical, highly spatially modulated grid cells, and calbindin-containing pyramidal cells (PCs) which display spatial tuning (Sargolini et al, 2006; Tang et al, 2014; Tennant et al, 2018). In the dorsal mEC, grid fields are small with higher spatial resolution, whereas in the ventral mEC, grid fields are larger, perhaps corresponding to different roles in spatial navigation (Hafting et al, 2005; Brun et al, 2008)

Methods

Results

Conclusion