Neurocan Contributes to Perineuronal Net Development

Perineuronal nets (PNs) are matrix molecule assemblies surrounding neuronal somata, dendrites and axon initial segments in a lattice-like appearance. PN molecules are involved in many structural and physiological processes during development and in adulthood, suggesting a crucial role in normal brain function. Neurocan, as one of the main PN proteoglycans, is suggested to control important developmental processes of neuronal tissue. This statement relies on thorough and excellent experimental work mainly conducted in reduced systems, such as cell cultures. However, previous data collected in neurocan-deficient mice do not seem to support neurocan's role in development since brain development in general and the formation of PNs especially in the hippocampus were reported to be undisturbed in neurocan-deficient mice. Here, we aim to re-address the role of neurocan in developmental processes by investigating the influence of neurocan on PN formation in the medial nucleus of the trapezoid body, a PN-enriched nucleus in the auditory brainstem, using neurocan-deficient mice. Immunohistochemical and biochemical analyses demonstrate that neurocan controls the regulation of PN development by influencing mRNA and protein quantity of various PN molecules. Resulting alterations in PN fine structure are critical for PN function as estimated by reduced amount of GAD65/67 and prolongation of synaptic transmission delay of calyx of Held synapses. Thus, neurocan contributes to proper PN formation and synapse physiology in the MNTB.