Differential expression of membrane conductances underlies spontaneous event initiation by rostral midline neurons in the embryonic mouse hindbrain.

摘要

Spontaneous activity is expressed in many developing CNS structures and is crucial in correct network development. Previous work using [Ca(2+)](i) imaging showed that in the embryonic mouse hindbrain spontaneous activity is initiated by a driver population, the serotonergic neurons of the nascent raphe. Serotonergic neurons derived from former rhombomere 2 drive 90% of all hindbrain events at E11.5. We now demonstrate that the electrical correlate of individual events is a spontaneous depolarization, which originates at the rostral midline and drives events laterally. Midline events have both a rapid spike and a large plateau component, while events in lateral tissue comprise only a smaller amplitude plateau. Lateral cells have a large resting conductance and are highly coupled via neurobiotin-permeant gap junctions, while midline cells are significantly less gap junction-coupled and uniquely express a T-type Ca(2+) channel. We propose that the combination of low resting conductance and expression of T-type Ca(2+) current is permissive for midline neurons to acquire the initiator or driver phenotype, while cells without these features cannot drive activity. This demonstrates that expression of specific conductances contributes to the ability to drive spontaneous activity in a developing network.