Electrical activity of nerve cells appears to have roles in the developmental wiring of the nervous system and neuronal differentiation. Thus, understanding neural development necessarily requires understanding the regulation and role of neural excitability during development. Various extrinsic modulatory factors alter neuronal survival and excitability. Changes in excitability may be a mechanism through which these extrinsic factors exert their control over neuronal survival and/or differentiation. Recent data suggest that the electrophysiological development of a class of Xenopus primary spinal neurons, most likely neurons, is affected by factors extrinsic to the cell. This proposal will focus on the extrinsic modulation of an mRNA that encodes a specific voltage-gated ion channel (Kv2.2) that is differentially regulated in vitro compared with in vivo in these Xenopus neurons. There are three independent specific aims: (1) Characterize the temporal pattern of Kv2.2 mRNA expression in vivo and in vitro; (2) Determine the identity of Kv2.2- expressing neurons and assess the effects of potential target cells on Kv2.2 mRNA in vitro and (3) Delineate the specific window of time (critical period) during which neurons must reside in vivo to enable appropriate Kv2.2 expression in vitro. Examination of the developmental regulation of neuronal excitability may provide a foundation for study of some pervasive developmental disorders. In addition, this research could lead to treatment of motor neuron pathologies such as amyotrophic lateral sclerosis, through illumination of the roles of extrinsic factors and excitability in neuronal survival.
