Regulation of gap junction coupling in the developing neocortex.

In the developing mammalian, neocortex gap junctions represent a transient, metabolic, and electrical communication system. These gap junctions may play a crucial role during the formation and refinement of neocortical synaptic circuitries. This article focuses on two major points. First, the influence of gap junctions on electrotonic cell properties will be considered. Both the time-course and the amplitude of synaptic potentials depend, inter alia, on the integration capabilities of the postsynaptic neurons. These capabilities are, to a considerable extent, determined by the electrotonic characteristics of the postsynaptic cell. As a consequence, the efficacy of chemical synaptic inputs may be crucially affected by the presence of gap junctions. The second major topic is the regulation of gap junctional communication by neurotransmitters via second messenger pathways. The monoaminergic neuromodulators dopamine, noradrenaline, and serotonin reduce gap junction coupling via activation of two different intracellular signaling cascades--the cAMP/protein kinase A pathway and the IP3/Ca2+/protein kinase C pathway, respectively. In addition, gap junctional communication seems to be modulated by the nitric oxide (NO)/cGMP system. Since NO production can be stimulated by glutamate-induced calcium influx, the NO/cGMP-dependent modulation of gap junctions might represent a functional link between developing glutamatergic synaptic transmission and the gap junctional network. Thus, it might be of particular importance in view of a role of gap junctions during the process of circuit formation.