Markus Morawski: The impact of proteoglycans of perineuronal nets on the ultrafast synaptic transmission in the auditory system

About 20% of central nervous system (CNS) volume is extracellular matrix (ECM) which is composed of specific macromolecules filling the extracellular space and being considered as an essential determinant of the organization and function of the CNS. Perineuronal nets (PNs) and their constructive proteoglycans are classified as a unique and specialized composition of this ECM surrounding the soma, dendrites and axon initial segments of a particular subset of neurons. In the last twenty years many researchers speculated about the potential contribution of PNs and its components to synaptic activity and synaptic transmission and also more generally to the functionality of the brain. However, there are hardly any reports providing experimental verification of this theory. The main scope of this proposal is to experimentally approach this issue and to clarify the significance of PNs for synaptic transmission. The auditory system will be the main study target due to the exceptionally high proportions of PN-bearing neurons. Supported by our preliminary data we hypothesize that especially proteoglycans of PNs, such as brevican, control the speed and efficiency of glutamatergic synaptic transmission at synapses in the ascending auditory system, and connected to this are important for normal hearing. To address this hypothesis we will apply in vivo and in vitro electrophysiology, complemented by electron microscopy and immunohistochemistry, The experiments will be conducted in transgenic mouse lines which are deficient for specific proteoglycans of the perineuronal nets (brevican, aggrecan and neurocan).
This project will provide novel insights into the functions and significance of proteoglycans of PNs for ultrafast synaptic transmission and hearing.