The interplay between two major forebrain structures - cortex and subcortical striatum - is critical for flexible, goal-directed action. Traditionally, it has been proposed that striatum is critical for selecting what type of action is initiated while the primary motor cortex is involved in the online control of movement execution. Recent data indicates that striatum may also be critical for specifying movement execution. These alternatives have been difficult to reconcile because when comparing very distinct actions, as in the vast majority of work to date, they make essentially indistinguishable predictions. Here, we develop quantitative models to reveal a somewhat paradoxical insight: only comparing neural activity during similar actions makes strongly distinguishing predictions. We thus developed a novel reach-to-pull task in which mice reliably selected between two similar, but distinct reach targets and pull forces. Simultaneous cortical and subcortical recordings were uniquely consistent with a model in which cortex and striatum jointly specify flexible parameters of action during movement execution.

Chemical neurotransmission constitutes one of the fundamental modalities of communication between neurons. Monitoring release of these chemicals has traditionally been difficult to carry out at spatial and temporal scales relevant to neuron function. To understand chemical neurotransmission more fully, we need to improve the spatial and temporal resolutions of measurements for neurotransmitter release. To address this, we engineered a chemi-sensitive, two-dimensional nanofilm that facilitates subcellular visualization of the release and diffusion of the neurochemical dopamine with synaptic resolution, quantal sensitivity, and simultaneously from hundreds of release sites. Using this technology, we were able to monitor the spatiotemporal dynamics of dopamine release in dendritic processes, a poorly understood phenomenon. We found that dopamine release is broadcast from a subset of dendritic processes as hotspots that have a mean spatial spread of ≈3.2 µm (full width at half maximum) and are observed with a mean spatial frequency of 1 hotspot per ≈7.5 µm of dendritic length. Major dendrites of dopamine neurons and fine dendritic processes, as well as dendritic arbors and dendrites with no apparent varicose morphology participated in dopamine release. Remarkably, these release hotspots colocalized with Bassoon, suggesting that Bassoon may contribute to organizing active zones in dendrites, similar to its role in axon terminals.