Characterizing striatum-dopamine interactions in freely-moving mice

Choosing what to do at any given moment is a key brain function largely accomplished by a deep brain region called the striatum. The striatum is a major target of dopamine, a neurotransmitter that regulates reward learning and goal-directed behaviors. Interestingly, the striatum contains specialized regions called ‘patches’ (or striosomes), which simultaneously project to dopamine neurons and suppress dopamine release, acting as a negative feedback loop. Recent studies have demonstrated an important role of striatal patches in action selection, making them well-suited as a putative candidate for sculpting dopamine output in the striatum. Furthermore, previous work from our lab suggests that activation of patches is sufficient to suppress dopamine release in anesthetized mice. However, no studies have fully characterized striatum-dopamine or patch-dopamine interactions during behavior. To examine this, we utilize a novel technique called fiber photometry to detect subsecond fluctuations in striatal signaling via calcium indicators (GCaMP6s/GCaMP8m) and extracellular dopamine levels via dopamine sensors (GRAB-DAr) in freely-moving mice. We first ask how activity in these regions change with locomotor activity in mice, and will nextly assess their effect on reward-related behavioral tasks. Early results suggest that dopamine release may upregulate striatal activity and that striatal activity is linked to locomotor behaviors. In addition, we expect increases in patch activity to be associated with dopamine decreases, or smaller amplitude dopamine signals, to reflect its inhibitory function on dopamine neurons. Together, this work will provide novel insight into how the striatum and dopamine systems coordinate their activity to modify ongoing actions.