An optogenetics method has been used to stimulate the repair of a single neuronal circuit in zebrafish larvae. The method could have future therapeutic applications as a treatment for neuropathies in humans and other vertebrates. Environmental insult, disease or trauma can affect the physical integrity of neuronal circuits, and the inability of many neurons to regenerate injured axons leads to irreversible neural dysfunction, said researchers from Helmholtz Zentrum München, the German research center for environmental health. Key for the researchers' success was the messenger molecule cAMP, which is produced by the enzyme adenylyl cyclase and is known to promote axonal regrowth. 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 predefined neurons at selected time points in whole specimens, the researchers said. Technologies to guide neuronal repair in time and space would enable studies of neural-circuit recovery with unprecedented resolution. For their experiment, the scientist used a form of adenylyl cyclase inducible by blue light, enabling specific modulation of the production of cAMP in cells expressing this enzyme. They applied the system to zebrafish larvae that had interrupted sensory lateralis nerves. "When blue light was shone on severed nerves that expressed a photoactivatable adenylyl cyclase, their repair was dramatically increased," said doctoral student Yan Xiao. "While untreated nerve terminals only made synapses again in 5 percent of the cases, about 30 percent did after photostimulation." "Our results show for the first time how the repair of a complex neural circuit in a whole animal can be promoted remotely by the use of light," said Hernán López-Schier, head of the sensory biology and organogenesis research unit at Helmholtz Zentrum München.