Brain mechanisms of reinforcement and reward underlie major human diseases such as
drug addiction (1), and contribute to a wide variety of normal processes ranging from goal-directed behavior (2) to
decision making (3). However, in these and many other complex behaviors, technological limitations have prevented spatiotemporally precise investigation and control over the
biochemical signaling mechanisms that may mediate these processes. Here, we report the development of a versatile family of optical tools (optoXRs) for recruiting and controlling, with high spatiotemporal precision, receptor-initiated
biochemical pathways within genetically-specified cell types in vivo. In particular, we have characterized in
neural systems two optically addressable receptor pathways, opto-_1AR and opto-_2AR, and tested the potential role of the resulting recruited
signaling pathways within
nucleus accumbens neurons in modulating reward behavior in freely-moving adult
mice. We find that these two pathways exert opposite effects on spike firing in
nucleus accumbens; that stimulation of the Gq -linked opto-_1AR in
accumbens neurons by itself suffices to induce place preference in an operant optical conditioning paradigm; and that recruitment of this
signaling pathway in these
neurons is more tightly linked to behaviorally-defined reward than changes in spiking rate itself. The optoXR approach allows testing of hypotheses regarding the causal impact of
biochemical signaling in freely moving animals, in a cell type-specific and temporally-precise manner.
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Neuro (2006); Carelli RM, Wightman RM. Curr Opin Neurobiol (2004).
2
Grace AA, Floresco SB, Goto Y, et al.
Trends in Neuroscience (2007).
3
Gold JI, Shadlen MN. Ann Rev
Neuro (2007); Schultz W. Ann Rev Psych (2006); Rangel A, Camerer C, Montague PR. Nat Rev
Neuro (2008).
