Optogenetic stimulation of neuronal repair

Abstract

Environmental insult, disease or trauma can affect the physical integrity of neuronal circuits, and the inability of many neurons to regenerate injured axons invariably leads to irreversible neural dysfunction. The conserved second messenger cyclic adenosine monophosphate (cAMP) can promote axonal re-growth. Widely used pharmacological or genetic approaches to increase intracellular levels of cAMP are often inadequate for precise neural-circuit reconstruction because their activity cannot be easily timed to specific target cells. These shortcomings have prevented the controlled repair of pre-defined neurons at selected time points in whole specimens. Thus, technologies to guide neuronal repair in time and space would enable studies of neural-circuit recovery with unprecedented resolution. Towards this aim, we have implemented a proof-of-principle optogenetic method to promote the selective regeneration of refractory axons in a living vertebrate.