Establishing the causal relationships between brain function and behavior is one of the most important goals in neuroscience research. Traditionally, this has been accomplished with electrical stimulation or lesioning techniques that nonselectively activate or ablate the neural tissue, or by microinjections of drugs, which often selectively activate or inhibit specific neurons, but do so on a timescale irrelevant to neuronal firing. Although these techniques have been crucial in defining the gross neuroanatomical pathways that mediate behavior, they have had limited success in determining the specific synaptic connections and cell types that mediate a given behavioral response. With the recent advances in the emerging field of optogenetics, it is now possible to selectively introduce light-gated ion channels and pumps into genetically defined populations of neurons to selectively stimulate or inhibit neuronal circuit elements with light. Although optogenetics is still in its infancy, its use has already revealed important and novel information on neural function that was inaccessible with traditional techniques.

Transient inhibition of circuit components could potentially be even more valuable for assaying the neural basis of behavior. By introducing the bacteria-derived light-sensitive chloride pump Halorhodopsin (NpHR) into select neurons, optical inhibition of neural activity is now possible on a millisecond timescale (Zhang et al, 2007). NpHR, which is maximally activated by yellow light (∼590 nm), yields an inward chloride conductance capable of hyperpolarizing neurons and inhibiting firing. NpHR can potentially be used in combination with ChR2 to selectively inhibit or excite subpopulations of neurons with different wavelengths of light during behavioral tasks. Taken together, these emerging tools may help reshape systems neuroscience and greatly aid our understanding of the neural circuitry underlying addiction and psychiatric disease.

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