Brain circuitry outside the synaptic cleft

A growing body of experimental evidence suggests that astroglia, and possibly microglia, play an important part in regulating synaptic networking of the brain. It has also emerged that extracellular matrix (ECM) structures that enwrap synaptic connections can generate molecular signals affecting both neuronal and glial activity. Thus it appears that the mechanism of information processing in the brain, which has hitherto been associated almost exclusively with neural circuits, could also involve informative signal exchange outside the synaptic cleft. In this Theme Issue, research teams including leading experts on astroglia–neuron communication and on ECM signalling report their recent findings, share their views and discuss future conceptual advances in the field. Potential implications for drug development and new therapeutic targets with regard to some common neurological conditions are discussed throughout the issue.