Voltage-gated Na+ channels in neuronal development

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Mice that have a mutation in Scn8a, a gene that encodes a voltage-gated sodium channel, are blind according to electroretinogram (ERG) recordings (Côté et al. 2005 J Neurosci 25:5046-50). Interestingly, the blindness originates at the level of the photoreceptors, the cells of the retina that initially capture light. This observation is puzzling for two reasons 1) photoreceptors are known to use graded 'analog'-type signals to convey information to other cells while Scn8a is involved in the production and propagation of action potentials (all-or-nothing 'binary'-type signals), 2) the expression of Scn8a in photoreceptors is very weak. For these reasons, we favor the hypothesis that other cell types in the retina that strongly express Scn8a need to communicate directly or indirectly with the photoreceptors during a critical period of development. The long-term goal of the proposed research program is to uncover the cellular pathways that link Scn8a and photoreceptor function and to determine how VGSCs are involved in the maturation of other neural cell types. Knowledge gained on the normal development of the retina and the nervous system during the course of this research program will aid in devising strategies to promote regeneration in states of trauma and to counter degenerative diseases.