The regulation and role of neuronal gap junctions during development.

Coupling of neurons by electrical synapses (gap junctions) transiently increases in the mammalian CNS during development and plays a role in a number of developmental events, including neuronal death. The coupling subsequently decreases and remains low in the adult, confined to specific subsets of neurons. In a recent study we have demonstrated that the developmental increase in neuronal gap junction coupling is regulated by the balance between the activity of two neurotransmitter receptors, group II metabotropic glutamate receptors (mGluR) and GABA(A) receptors. Specifically, we found that activation of group II mGluRs induces the developmental increases in neuronal gap junction coupling and expression of connexin 36 (Cx36; neuronal gap junction protein) and activation of GABA(A) receptors counteracts to these increases. We also established that the regulation by both neurotransmitter receptors is via a neuron-restrictive silencer element in the Cx36 gene promoter and the 3'-untranslated region of the Cx36 mRNA. Importantly, we demonstrated that mechanisms for the developmental increase in neuronal gap junction coupling directly control the death/survival mechanisms in developing neurons.