UC San Diego

Making decisions is a critical part of adaptive behavior across many species. Volitional decision-making, otherwise known as action control, is disrupted across many disease states, and thus studying the neurobiological circuits that support decision-making can help inform future therapeutics. This thesis examines two nodes known to be critical for goal-directed decision-making: the striatum, and the mediodorsal thalamus. Chapter 1 investigated changes to the striatum after chronic alcohol exposure. Chronic alcohol exposure has been shown to alter goal-directed control over behavior. We examined calcium activity using fiber photometry in three major cell types, D1 spiny projection neurons, D2 spiny projection neurons, and PV interneurons in striatum after chronic alcohol exposure. Fiber photometry in the striatum does not necessarily reflect changes in somatic activity or action potentials and instead reflects a sum of non-somatic changes in calcium. Thus, the calcium changes we observed were sums of the changes in input to each cell type after chronic alcohol exposure. We saw increased calcium activity in the direct pathway during action-related behavior in contrast to decreases in activity in indirect pathway and local inhibitory PV neurons. Chapter 2 focused on one of striatum’s thalamic partners, the mediodorsal thalamus. We investigated the role of mediodorsal thalamic input in striatum during a decision-making task. We examined MD terminal activity in striatum during an action task and found significant modulation around actions depending on if the action would be successful. We also found that inhibition of the MD-DMS circuit disrupts flexible learning of new action rules under a change in contingency. These studies demonstrate changes to input in striatum after chronic alcohol exposure where action control is altered and show that mediodorsal thalamic input to striatum is critical for learning new contingencies.