Structural development and dorsoventral maturation of the medial entorhinal cortex.

Saikat Ray,Michael Brecht

doi:10.7554/elife.13343

Abstract

We investigated the structural development of superficial-layers of medial entorhinal cortex and parasubiculum in rats. The grid-layout and cholinergic-innervation of calbindin-positive pyramidal-cells in layer-2 emerged around birth while reelin-positive stellate-cells were scattered throughout development. Layer-3 and parasubiculum neurons had a transient calbindin-expression, which declined with age. Early postnatally, layer-2 pyramidal but not stellate-cells co-localized with doublecortin - a marker of immature neurons - suggesting delayed functional-maturation of pyramidal-cells. Three observations indicated a dorsal-to-ventral maturation of entorhinal cortex and parasubiculum: (i) calbindin-expression in layer-3 neurons decreased progressively from dorsal-to-ventral, (ii) doublecortin in layer-2 calbindin-positive-patches disappeared dorsally before ventrally, and (iii) wolframin-expression emerged earlier in dorsal than ventral parasubiculum. The early appearance of calbindin-pyramidal-grid-organization in layer-2 suggests that this pattern is instructed by genetic information rather than experience. Superficial-layer-microcircuits mature earlier in dorsal entorhinal cortex, where small spatial-scales are represented. Maturation of ventral-entorhinal-microcircuits - representing larger spatial-scales - follows later around the onset of exploratory behavior.

Highlights

The representation of space in the rodent brain has been investigated in detail
We investigated the development of the architecture of the medial entorhinal cortex (MEC) and parasubiculum (PaS), two key structures in the cortico-hippocampal system
The clustering of layer 2 MEC calbindin+ neurons into patches is an early developmental event, and key aspects of the grid-layout of calbindin+ neurons are already present at birth

Summary

Introduction

The representation of space in the rodent brain has been investigated in detail. The functional development of spatial response properties has been investigated in the cortico-hippocampal system (Ainge and Langston, 2012; Wills et al, 2014), with studies suggesting the early emergence of head-directional selectivity (Tan et al, 2015; Bjerknes et al, 2015), border representation (Bjerknes et al, 2014) and place cell firing, but a delayed maturation of grid cell discharges (Wills et al, 2010; Langston et al, 2010).Even though there is information on the emergence of functional spatial properties in the hippocampal formation, remarkably little is known about the structural development of the microcircuits which bring about these properties. The functional development of spatial response properties has been investigated in the cortico-hippocampal system (Ainge and Langston, 2012; Wills et al, 2014), with studies suggesting the early emergence of head-directional selectivity (Tan et al, 2015; Bjerknes et al, 2015), border representation (Bjerknes et al, 2014) and place cell firing, but a delayed maturation of grid cell discharges (Wills et al, 2010; Langston et al, 2010). Layer 2 of MEC contains two types of principal cells, stellate and pyramidal cells (Alonso and Klink, 1993; Germroth et al, 1989). Pyramidal neurons in layer 2 of MEC can be identified by calbindinimmuno-reactivity (Varga et al, 2010) and are clustered in patches across various mammalian species (Fujimaru and Kosaka, 1996; Ray et al, 2014; Naumann et al, 2016), while stellate cells can

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