Reorganization of Synaptic Connections and Perineuronal Nets in the Deep Cerebellar Nuclei of Purkinje Cell Degeneration Mutant Mice.

M. Blosa,C. Bursch,C. Janke,C. Jäger,M. Morawski,M. Holzer,T. Arendt,S. Weigel,R. T. Matthews

doi:10.1155/2016/2828536

Abstract

The perineuronal net (PN) is a subtype of extracellular matrix appearing as a net-like structure around distinct neurons throughout the whole CNS. PNs surround the soma, proximal dendrites, and the axonal initial segment embedding synaptic terminals on the neuronal surface. Different functions of the PNs are suggested which include support of synaptic stabilization, inhibition of axonal sprouting, and control of neuronal plasticity. A number of studies provide evidence that removing PNs or PN-components results in renewed neurite growth and synaptogenesis. In a mouse model for Purkinje cell degeneration, we examined the effect of deafferentation on synaptic remodeling and modulation of PNs in the deep cerebellar nuclei. We found reduced GABAergic, enhanced glutamatergic innervations at PN-associated neurons, and altered expression of the PN-components brevican and hapln4. These data refer to a direct interaction between ECM and synapses. The altered brevican expression induced by activated astrocytes could be required for an adequate regeneration by promoting neurite growth and synaptogenesis.

Highlights

The function of the nervous system is based on a precise composition and maintenance of a neuronal and synaptic network
In a mouse model for Purkinje cell degeneration, we examined the effect of deafferentation on synaptic remodeling and modulation of perineuronal net (PN) in the deep cerebellar nuclei
The neurons of the deep cerebellar nuclei (DCN) and lateral vestibular nucleus (LVN), which are innervated by the cerebellar Purkinje cells (PCs), are affected as well

Summary

Introduction

The function of the nervous system is based on a precise composition and maintenance of a neuronal and synaptic network. Once the adult connectivity is established, plasticity of some synaptic contacts is greatly diminished Functional alterations as they occur in many brain disorders are accompanied by remodeling of neuronal structures, changes in neuronal activity, and loss of neuronal molecules [1,2,3]. A specialized form of the extracellular matrix, the perineuronal net, often shows alterations in neurodegenerative diseases [8,9,10,11] and acute brain injuries [7, 11,12,13,14,15] and is suggested to prevent regeneration These perineuronal nets (PNs) enclose the cell bodies and the proximal dendrites of specialized neurons thereby embedding the contacting synaptic boutons [16,17,18]. The cytochemical analyses showed that the molecular composition of PNs has changed and revealed that brevican and hapln are prone to the degeneration processes and may influence the regeneration of the injured tissue

Experimental Procedures

Results

Discussion

Conclusions