UCSF

Much of the behavior of humans and other animals is directed towards seeking out edible, social, cognitive or drug rewards. Dopamine, a neurotransmitter released by a handful of cells in the brain, is known to be essential for reward-seeking behavior. Yet despite decades of focused investigation, the nature of its influence remains a matter of considerable debate. The precise roles that dopamine neurons play are likely to depend on their afferent and efferent connectivity, the timing and length of neural activation, and the features of the behavior under investigation. Accordingly, it is becoming increasingly appreciated that delineating the specific contributions of dopamine neurons to cellular, circuit, and systems-level phenomena will require more sophisticated control over their patterns of activity than conventional electrophysiological and pharmacological techniques can provide.

Recently developed optogenetic tools hold great promise for disentangling these complex issues. In Chapter 2, I describe the development and characterization of a novel transgenic rat line that permits selective opsin expression in ventral tegmental area dopamine neurons, as well as other catecholamine neurons in the rat brain. I then utilize this tool to determine if temporally-precise patterns of dopamine neuron activity are causally related to appetitive behaviors. In Chapter 3, I present data from a series of experiments designed to clarify the role of ventral tegmental area dopamine neurons, or their major efferent projection to the nucleus accumbens, in positive reinforcement. Then in Chapter 4, I describe experiments designed to determine if ventral tegmental area dopamine neurons are capable of supporting associative cue-reward learning. Collectively, my results demonstrate that ventral tegmental dopamine neurons are sufficient to reinforce instrumental responding, and that their ability to influence reward-seeking behavior is at least partly due to the fact that they can drive associative learning directly. As such, they represent an important advance in our understanding of the neural basis of learned appetitive behaviors.