The striatum is crucial for movement, learning and flexible behavior. Both dopamine (DA) and acetylcholine (ACh) play key roles in these functions. While the role of DA is relatively well established, that of ACh remains enigmatic. Cholinergic interneurons (CINs), the major source of striatal ACh, are involved in processing contextual information that guides flexible behavior. Locally, CINs also exert control over striatal DA release, hijacking DA axons and making them release ACh by activating nicotinic receptors near their terminals.
The central hypothesis of the grant is that CINs contribute to behavioral flexibility by dynamically orchestrating DA signaling in the striatum. Modeling the two processes of DA and ACh release in the striatum as activator-inhibitor reaction diffusion system gives rise to predictions concerning localized areas of increased concentration and traveling waves of DA and ACh. With the advent of genetically encoded biosensors, which permit ultrafast cellular resolution imaging of neuronal DA and ACh dynamics in mouse brain, this hypothesis will be tested in freely-moving mice.