The extracellular matrix (ECM) in the central nervous system plays an important role in neural development and Hebbian forms of plasticity. Here we highlight new functions of ECM glycans at the synaptic, neural network and behavioral levels. We show in vitro that removal of hyalurionic acid or heparan sulfates converts the normal network firing bursts and Ca2+ oscillations into long-lasting epileptiform “superbursts” and “superoscillations”. A plausible mechanism for these changes is homeostatic up-scaling of excitatory transmission induced by a deficit in L-type Ca2+ channel-mediated signaling during development. Another mechanism is activated by acute removal of chondroitin sulfates that impairs long-term potentiation by suppression of neuronal activity through modulation of specific K+ channels. In vivo, heparan sulfates are required for contextual fear conditioning and proper generation of theta- and gamma-oscillations in the hippocampus, supporting the view that the ECM is essential for learning and memory.