Perineuronal nets stabilize the grid cell network

Ane Charlotte Christensen,Marianne Fyhn,Halvard Sutterud,Halvard Sutterud,Mikkel Elle Lepperød,Svenn-Arne Dragly,Torkel Hafting,Jan Sigurd Blackstad,Kristian Kinden Lensjø

doi:10.1038/s41467-020-20241-w

Abstract

Grid cells are part of a widespread network which supports navigation and spatial memory. Stable grid patterns appear late in development, in concert with extracellular matrix aggregates termed perineuronal nets (PNNs) that condense around inhibitory neurons. It has been suggested that PNNs stabilize synaptic connections and long-term memories, but their role in the grid cell network remains elusive. We show that removal of PNNs leads to lower inhibitory spiking activity, and reduces grid cells’ ability to create stable representations of a novel environment. Furthermore, in animals with disrupted PNNs, exposure to a novel arena corrupted the spatiotemporal relationships within grid cell modules, and the stored representations of a familiar arena. Finally, we show that PNN removal in entorhinal cortex distorted spatial representations in downstream hippocampal neurons. Together this work suggests that PNNs provide a key stabilizing element for the grid cell network.

Highlights

Grid cells are part of a widespread network which supports navigation and spatial memory
The grid cell network in medial entorhinal cortex (MEC) has been under intense investigation since its discovery[7], but little is known about how grid cells achieve their extraordinary stability across time and environments
We show that enzymatic degradation of perineuronal nets (PNNs) changes grid cell network dynamics by altering the temporal relationship between grid cells and impairing representations of novel environments

Summary

Introduction

Grid cells are part of a widespread network which supports navigation and spatial memory. Stable grid patterns appear late in development, in concert with extracellular matrix aggregates termed perineuronal nets (PNNs) that condense around inhibitory neurons. It has been suggested that PNNs stabilize synaptic connections and long-term memories, but their role in the grid cell network remains elusive. We show that removal of PNNs leads to lower inhibitory spiking activity, and reduces grid cells’ ability to create stable representations of a novel environment. Grid cells provide input to the hippocampus[8] and are assumed to be the primary determinant of hippocampal place cell firing[3,5,9]. Whether PV+ inhibitory neurons in MEC play a similar role for development of the grid cell network remains elusive. By the time PNNs in sensory cortex are fully mature, plasticity in the local network is strongly reduced

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Conclusion