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.

Center for Integrative Brain Research Seattle Children's Research Institute 1900 9th Ave Seattle WA 98125 USA

Center for Laser Microscopy Institute for Physiology and Biochemistry Jean Giaja Faculty of Biology University of Belgrade 11000 Belgrade Serbia

Laboratory of Biomechanics and Biomedical Engineering Department of Mechanical Engineering and Aeronautics University of Patras 26504 Patras Greece

Light Microscopy Core Facility Institute of Molecular Genetics CAS Prague 142 20 Czech Republic

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