National Science Foundation (NSF)

Over the last decade, sophisticated genetic tools have been developed that allow control and monitoring of neurons’ electrical activity using light alone. “Optogenetics”, as this area of technology has become known, has revolutionized most areas of neuroscience by allowing specific components of complex neural systems to be individually controlled or monitored. Optogenetics is only useful, however, if the optogenetic molecules can be specifically expressed in functionally meaningful groups of neurons, instead of broadly in all the diverse neuron types that are present in any brain region. This requirement has confined their use almost entirely to genetically modified (“transgenic”) mice and rats. These rodent studies have been extraordinarily successful, being used in thousands of neuroscience laboratories worldwide and providing the basis for numerous high-impact discoveries. However, the approach of using transgenic animals has three major disadvantages. First, the production and maintenance of transgenic rodents is very expensive. Second, even within transgenic rodents, it allows the optogenetic study and manipulation of only one or two cell types at a time, preventing powerful combinatorial experiments in which different neuron types are independently controlled within the same tissue. These combinatorial experiments will be critical for deciphering the complex interactions between cell types. Third, it restricts the experiments to rodents, preventing studies in other important taxa including primates, in which optogenetic experimentation during complex cognitive tasks would almost certainly provide major insights into the neural circuitry underlying cognition.

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