Synaptic coupling of inner ear sensory cells is controlled by brevican-based extracellular matrix baskets resembling perineuronal nets

Mandy Sonntag,Sophie Schmidt,Dietmar Hecker,Gudrun Seeger,Markus Morawski,Katja Reimann,Tobias Eckrich,Thomas Arendt,Jutta Engel,Bernhard Schick,Maren Blosa,Kerstin Blum

doi:10.1186/s12915-018-0566-8

Mandy Sonntag, Sophie Schmidt + Show 10 more

Open Access

https://doi.org/10.1186/s12915-018-0566-8

Copy DOI

Journal: BMC Biology	Publication Date: Sep 26, 2018
Citations: 24	License type: open-access

Affiliation: Leipzig University, Saarland University

Abstract

BackgroundPerineuronal nets (PNNs) are specialized aggregations of extracellular matrix (ECM) molecules surrounding specific neurons in the central nervous system (CNS). PNNs are supposed to control synaptic transmission and are frequently associated with neurons firing at high rates, including principal neurons of auditory brainstem nuclei. The origin of high-frequency activity of auditory brainstem neurons is the indefatigable sound-driven transmitter release of inner hair cells (IHCs) in the cochlea.ResultsHere, we show that synaptic poles of IHCs are ensheathed by basket-like ECM complexes formed by the same molecules that constitute PNNs of neurons in the CNS, including brevican, aggreccan, neurocan, hyaluronan, and proteoglycan link proteins 1 and 4 and tenascin-R. Genetic deletion of brevican, one of the main components, resulted in a massive degradation of ECM baskets at IHCs, a significant impairment in spatial coupling of pre- and postsynaptic elements and mild impairment of hearing.ConclusionsThese ECM baskets potentially contribute to control of synaptic transmission at IHCs and might be functionally related to PNNs of neurons in the CNS.

Highlights

Perineuronal nets (PNNs) are specialized aggregations of extracellular matrix (ECM) molecules surrounding specific neurons in the central nervous system (CNS)
Distribution of PNN-constituting proteoglycans and link proteins in the cochlea Given the sparse information on the expression of the Chondroitin-sulfated proteoglycan (CSPG) brevican, aggrecan, and neurocan, as well as HAPLN1, HAPLN4, and tenascin-R in the cochlea, the initial aim of the present study was to test whether these typical constituents of PNNs can be identified within cochlear tissue and whether these components are associated with cochlear sensory cells
All of the tested CSPGs as well as HAPLN1 could be identified in cross-section of the cochlea (Fig. 1), even brevican (Fig. 1a) and neurocan (Fig. 1c), which have been presumed to be specific for the brain [26,27,28,29]

Summary

Introduction

Perineuronal nets (PNNs) are specialized aggregations of extracellular matrix (ECM) molecules surrounding specific neurons in the central nervous system (CNS). PNNs are supposed to control synaptic transmission and are frequently associated with neurons firing at high rates, including principal neurons of auditory brainstem nuclei. A specialized form of the ECM are the perineuronal nets (PNNs), a pericellular cover that tightly enwraps somata, proximal dendrites, and axon initial segments of specific neurons thereby leaving meshes occupied by synaptic terminals. PNNs are assumed to contribute to high-frequency neuronal activity and synaptic transmission [16, 17]. They typically surround fast-spiking, parvalbumin-positive interneurons within the cortex [9, 16, 18]. PNNs are densely expressed within all auditory brainstem nuclei, thereby surrounding various neuron types such as glutamatergic bushy cells in the cochlear nucleus or glycinergic principal neurons in the medial nucleus of the trapezoid body (MNTB) (for review see Sonntag et al BMC Biology (2018) 16:99

Objectives

Methods

Results

Discussion

Conclusion