Abstract
The extracellular matrix (ECM) of the brain plays a crucial role in providing optimal conditions for neuronal function. Interactions between neurons and a specialized form of ECM, perineuronal nets (PNN), are considered a key mechanism for the regulation of brain plasticity. Such an assembly of interconnected structural and regulatory molecules has a prominent role in the control of synaptic plasticity. In this review, we discuss novel ways of studying the interplay between PNN and its regulatory components, particularly tenascins, in the processes of synaptic plasticity, mechanotransduction, and neurogenesis. Since enhanced neuronal activity promotes PNN degradation, it is possible to study PNN remodeling as a dynamical change in the expression and organization of its constituents that is reflected in its ultrastructure. The discovery of these subtle modifications is enabled by the development of super-resolution microscopy and advanced methods of image analysis.
Highlights
The extracellular matrix (ECM) has an instrumental role in the regulation of function and homeostasis of the nervous system
These molecules associated with perineuronal nets (PNN) structure and function are hyaluronic acid (HA), chondroitin sulfate proteoglycans (CSPG; including four members of the lectican family: aggrecan, brevican, neurocan and versican), link proteins and glycoproteins tenascin R (TnR) and tenascin C
Digesting HA in the rat cultured hippocampal network leads to hyperexcitability, an epileptic form of activity that was suppressed by blocking amino3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and L-type voltage dependent Ca2+ channels (L-VDCC), supporting the role of PNN constituents in optimizing neuronal networks through the control of synaptic inputs [78]
Summary
The extracellular matrix (ECM) has an instrumental role in the regulation of function and homeostasis of the nervous system. ECM can exist in a form of condensed web around the neuron and its proximal dendrites, which was first recognized in 1898 by Camillo Golgi in the cat cortex. He named those specific reticular structures perineuronal nets (PNN) [1]. Assumed to function as a rigid mechanical anchor for the cells, PNN were later recognized as long-lasting structures that restrict plasticity and set neuronal circuits’. We discuss novel ways of studying the interplay between PNN and their regulatory components, taking into account the growing body of literature regarding the relationship between prominent plasticity regulators, through their developmental, behavioral and functional correlations. We have dedicated a section of this review to the super-resolution imaging methods as indispensable tools for deciphering the complete topography of PNN and to follow their ultra-structural changes in physiological and pathological conditions
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