Neurotransmitters and gap junctions in developing neural circuits

A growing body of evidence suggests that highly correlated, spontaneous neu ral activity plays an important role in shaping connections in the developi ng nervous system prior to the maturation of sensory afferents. In this art icle we discuss the mechanisms involved in the generation and the regulatio n of spontaneous activity patterns in the developing retina and the develop ing neocortex. Spontaneous activity in the developing retina propagates acr oss the ganglion cell layer as waves of action potentials and drives rhythm ic increases in intracellular calcium in retinal neurons. Retinal waves are mediated by a combination of chemical synaptic transmission and gap juncti ons, and the circuitry responsible for generating retinal waves changes wit h age and between species. In the developing cortex, spontaneous calcium el evations propagate across clusters of cortical neurons called domains. Cort ical domains are generated by a regenerative mechanism involving second mes senger diffusion through gap junctions and subsequent calcium release from internal stores. The neocortical gap junction system is regulated by glutam ate-triggered second messenger systems as well as neuromodulatory transmitt ers, suggesting extensive interactions between synaptic transmission and in formation flow through gap junctions. The interaction between gap junctions and chemical synaptic transmission observed in these developing networks r epresent a powerful mechanism by which activity across large groups of neur ons can be correlated. (C) 2000 Elsevier Science B.V. All rights reserved.