The extracellular matrix regulates cortical layer dynamics and cross-columnar frequency integration in the auditory cortex

Mohamed El-Tabbal,Julia U Henschke,Max F K Happel,Hartmut Niekisch,Matthias Deliano,Renato Frischknecht,Eike Budinger

doi:10.1038/s42003-021-01837-4

Abstract

In the adult vertebrate brain, enzymatic removal of the extracellular matrix (ECM) is increasingly recognized to promote learning, memory recall, and restorative plasticity. The impact of the ECM on translaminar dynamics during cortical circuit processing is still not understood. Here, we removed the ECM in the primary auditory cortex (ACx) of adult Mongolian gerbils using local injections of hyaluronidase (HYase). Using laminar current-source density (CSD) analysis, we found layer-specific changes of the spatiotemporal synaptic patterns with increased cross-columnar integration and simultaneous weakening of early local sensory input processing within infragranular layers Vb. These changes had an oscillatory fingerprint within beta-band (25–36 Hz) selectively within infragranular layers Vb. To understand the laminar interaction dynamics after ECM digestion, we used time-domain conditional Granger causality (GC) measures to identify the increased drive of supragranular layers towards deeper infragranular layers. These results showed that ECM degradation altered translaminar cortical network dynamics with a stronger supragranular lead of the columnar response profile.

Highlights

In the adult vertebrate brain, enzymatic removal of the extracellular matrix (ECM) is increasingly recognized to promote learning, memory recall, and restorative plasticity
This study investigated the impact of acute removal of the extracellular matrix on the network physiology in the gerbil primary auditory cortex by local injection of the ECM-degrading enzyme hyaluronidase
Based on laminar current-source density (CSD) recordings we found that ECM removal altered the spatiotemporal profile of sensory-evoked synaptic population activity across cortical layers

Summary

Introduction

In the adult vertebrate brain, enzymatic removal of the extracellular matrix (ECM) is increasingly recognized to promote learning, memory recall, and restorative plasticity. We removed the ECM in the primary auditory cortex (ACx) of adult Mongolian gerbils using local injections of hyaluronidase (HYase). To understand the laminar interaction dynamics after ECM digestion, we used time-domain conditional Granger causality (GC) measures to identify the increased drive of supragranular layers towards deeper infragranular layers These results showed that ECM degradation altered translaminar cortical network dynamics with a stronger supragranular lead of the columnar response profile. Our data thereby shows that enzymatic removal of the ECM acutely biases the columnar synaptic network processing towards stronger recruitment of supragranular circuits and enhancement of lateral, cross-columnar interactions along with stronger drive from supragranular layers I/II towards deep infragranular layers VI which showed stronger drive towards layer Vb. Our study unraveled a mesoscopic cortical circuit mechanism of enhanced sensory integration in upper layers controlled by the ECM. These findings help to better understand existing behavioral findings linked to ECM modulation and may further allow to better understand certain pathological conditions of altered translaminar response characteristics, as for instance during sensory loss, and may help to optimize concepts for therapeutic approaches targeting the ECM

Methods

Results

Conclusion