Rapidly accumulating evidence indicates that the brain extracellular matrix (ECM), a complex molecular network surrounding all neural cells, plays a key role brain development and adult neural functions. The composition of the ECM varies through different developmental stages, a phenomenon likely to reflect its evolving functions regulating cell differentiation and migration, axonal outgrowth, and synaptic connectivity. Likewise, in the adult brain, the ECM region-specific composition and association of specialized ECM structures, such as perineuronal nets, with distinct neuronal populations, may reflect its functional heterogeneity and versatility. Exciting findings in recent years are beginning to shed light on the functions of perineuronal nets, one of the most extensively studied ECM forms. Their role during critical periods of development, malleability during learning processes, and regulation of synaptic plasticity, receptor trafficking and neuronal firing properties has provided important insights on brain plasticity and led to the suggestion that long term memories may in fact be stored in perineuronal nets.

Growing evidence also supports the involvement of the ECM in several diseases, such as epilepsy, traumatic brain injury, schizophrenia, bipolar disorder, anxiety and stress regulation, age related cognitive deficits including Alzheimer’s disease, drug addiction, and alcoholism. For instance, massive evidence shows a key role of the ECM in brain injuries, and marked decreases of perineuronal nets and anomalies of glial cells expressing ECM molecules have been reported in schizophrenia and bipolar disorder, affecting several brain regions. In addition, perineuronal nets have been suggested to have protective effects against oxidative stress, while at the same time being vulnerable to it, a phenomenon of great relevance to several brain disorders.

Despite these significant advances, the complexity and variety of the ECM neurochemical properties and functions is such that this field may be considered to be still in its infancy, while at the same time carrying the promise of transforming the field of neuroscience. This Frontiers Topic aims to create a multidisciplinary collection of recent advances on the ECM in adult normal brain and disease states. We invite authors to contribute original research articles as well as review articles that will represent current knowledge and stimulate investigation on the ECM and integrate this knowledge with efforts to better understand neural functions and brain disorders, as well as potential new therapeutic strategies.

Keywords: extracellular matrix, psychoses, addiction, epilepsy, aging

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