Ih is maturing: implications for neuronal development

Vast electrophysiological activity near resting potential, including rhythmic oscillatory activity, is a hallmark of many brain regions and a motor of the developing CNS. This activity is mediated and influenced by diverse receptor-operated and voltage-gated ion channels. In turn, these channels are modulated during the course of development by altering their density, distribution and properties. The hyperpolarization-activated and cyclic nucleotide-gated cation current, Ih, impacts on the resting membrane potential and is involved in the generation and modulation of neuronal oscillatory activity. Therefore, it is conceivable that Ih is well suited to govern the specific processes involved in activity-dependent neuronal development. Here, we review the evidence that maturation of Ih accounts, at least in part, for the control of membrane properties during neuronal development of various parts of the brain. The temporal and regional variations in Ih development might underlie the normal maturation of neuronal circuits and, consequently, the perturbations of this might account for some of the neuropathology of the brain. This review summarizes the evidence for the stage and localization dependence of Ih in CNS development with a focus on arborized cells with high dendritic Ih. Further, it outlines hypotheses on the contribution of Ih to neuronal and network maturation.