ERG conductance expression modulates the excitability of ventral horn GABAergic interneurons that control rhythmic oscillations in the developing mouse spinal cord

摘要

During antenatal development, the operation and maturation of mammalian spinal networks strongly depend on the activity of ventral\udhorn GABAergic interneurons that mediate excitation first and inhibition later. Although the functional consequence of GABA actions\udmay depend on maturational processes in target neurons, it is also likely that evolving changes in GABAergic transmission require\udfine-tuning in GABA release, probably via certain intrinsic mechanisms regulating GABAergic neuron excitability at different embryonic\udstages. Nevertheless, it has not been possible, to date, to identify certain ionic conductances upregulated or downregulated before birth in\udsuch cells. By using an experimental model with either mouse organotypic spinal cultures or isolated spinal cord preparations, the\udpresent study examined the role of the ERG current (IK(ERG) ), a potassium conductance expressed by developing, GABA-immunoreactive\udspinal neurons. In organotypic cultures, only ventral interneurons with fast adaptation and GABA immunoreactivity, and only after 1\udweek in culture, were transformed into high-frequency bursters by E4031, a selective inhibitor of IK(ERG) that also prolonged and made\udmore regular spontaneous bursts. In the isolated spinal cord in which GABA immunoreactivity and m-erg mRNA were colocalized in\udinterneurons, ventral root rhythms evoked by NMDA plus 5-hydroxytryptamine were stabilized and synchronized by E4031. All of these\udeffects were lost after 2 weeks in culture or before birth in coincidence with decreased m-erg expression. These data suggest that, during\udan early stage of spinal cord development, the excitability of GABAergic ventral interneurons important for circuit maturation depended,\udat least in part, on the function of IK(ERG).