Lectures and seminars StratNeuro Seminar: Dopamine, acetylcholine, and the value of effort

Dopamine, acetylcholine, and the value of effort

Effort is costly: given a choice, we tend to avoid it. But in many cases, effort is also valued. Experiments across species have demonstrated numerous examples where individuals value outcomes more after working harder for them. Despite accumulating evidence on the value of effort, however, little is known about the underlying neural substrates. We recently found that dopamine (DA) release in the core of the nucleus accumbens (NAc) tracked the effort required for reward, even when the reward was kept constant. When mice worked harder for reward, more DA was released in response to the cue denoting reward delivery. Our findings provide a plausible neural basis for how effort can augment a reward’s value. We are now situating our findings within the larger striatal circuit, discovering both what generates this DA effort signal (i.e., one synapse upstream), and how it modulates neural circuit function (i.e., one synapse downstream). In exciting preliminary data, we have discovered that cholinergic interneurons in the NAc encode effort, and their activity is essential to augment DA release in high-effort conditions. The cholinergic interneurons appear to inherit their effort encoding from long-range excitatory inputs, and when their signaling is disrupted, mice no longer work as hard for reward. In sum, we have begun to draw a circuit diagram for effort valuation, revealing how key cell types and neuromodulators interact in the striatum to drive effortful behavior.

Professor Neir Eshel's clinical focus is the full-spectrum mental health care of sexual and gender minorities, with particular interest in depression, anxiety, and the complex effects of trauma in this population. He works in collaboration with other primary care and mental health providers at the Stanford LGBTQ+ program.

His research interests (www.staarlab.com) include the use of optogenetic, electrophysiological, neuroimaging, and behavioral approaches to probe the neural circuits of reward processing, decision making, and social behavior. He has won multi-year grants from the National Institutes of Health, Burroughs-Wellcome Fund, Brain and Behavior Research Foundation, and Simons Foundation to further his research.