Neuronal Plasticity in the Juvenile and Adult Brain Regulated by the Extracellular Matrix

In brains of higher vertebrates, the delicate balance of structural remodeling and stabilization of neuronal networks changes over the life-span. While the juvenile brain is characterized by high structural plasticity, it is more restricted in the adult. During brain maturation, the occurrence of the extracellular matrix (ECM) is a critical step to restrict the potential for neuronal remodeling and regeneration, but providing structural tenacity. How this putative limitation of adult neuronal plasticity might impact on learning-related plasticity, lifelong memory reformation, and higher cognitive functions is subject of current research. Here, we summarize recent evidence that recognizes the ECM and its activity-dependent modulation as a key regulator of learning-related plasticity in the adult brain. We will first outline molecular concepts of enzymatic ECM modulation and its impact on synaptic plasticity mechanisms. Thereafter, the ECM’s role in converting juvenile to adult plasticity will be explained by several key studies in wild-type and genetic knockout animals. Finally, current research evidences the impact of ECM dynamics in different brain areas including neocortex on learning-related plasticity in the adult brain impacting on lifelong learning and memory. Experimental modulation of the ECM in local neuronal circuits further opens short-term windows of activity-dependent reorganization. Malfunctions of the ECM might contribute to a variety of neurological disorders. Therefore, experimental ECM modulation might not only promote complex forms of learning and cognitive flexible adaptation of valuable behavioral options, but has further implications for guided neuroplasticity with regenerative and therapeutic potential.