From molecules to behavior: Implications for perineuronal net remodeling in learning and memory

Perineuronal nets (PNNs) are condensed extracellular matrix (ECM) structures found throughout the central nervous system that regulate plasticity. They consist of a heterogeneous mix of ECM components that form lattice-like structures enwrapping the cell body and proximal dendrites of particular neurons. During development, accumulating research has shown that the closure of various critical periods of plasticity is strongly linked to experience-driven PNN formation and maturation. PNNs provide an interface for synaptic contacts within the holes of the structure, generally promoting synaptic stabilization and restricting the formation of new synaptic connections in the adult brain. In this way, they impact both synaptic structure and function, ultimately influencing higher cognitive processes. PNNs are highly plastic structures, changing their composition and distribution throughout life and in response to various experiences and memory disorders, thus serving as a substrate for experience- and disease-dependent cognitive function. In this review, we delve into the proposed mechanisms by which PNNs shape plasticity and memory function, highlighting the potential impact of their structural components, overall architecture, and dynamic remodeling on functional outcomes in health and disease. Perineuronal nets (PNNs) are condensed extracellular matrix structures consisting of multiple components joined together in a lattice-like fashion around particular neurons. In general, PNNs are thought to restrict plasticity (e.g., closure of critical periods, stabilization of synapses, and refinement of neural activity), subsequently impacting learning and memory processes. PNNs are highly dynamic and continuously fluctuate in composition and distribution throughout life and in response to various contexts, rendering them as a substrate for experience- and disease-dependent cognitive function.image