AI-Enabled Striatal Computation & Movement Control
Dopamine Signaling: From Sparse Release Sites to Distributed Computation
How does the striatum transform distributed neural activity into precise movement? We combine AI-based 3D behavior reconstruction, multi-fiber photometry, cell-type-resolved recordings and causal perturbations to connect neural population dynamics with natural actions. We employ synthetic-to-real learning to recover mouse pose across cameras and conditions; interpretable models then align movement states with dopamine, D1-MSN and D2-MSN activity across striatal regions. This multiscale framework reveals spatially organized movement codes, tests how dopamine depletion disrupts turning representations, and builds quantitative phenotypes for Parkinsonian circuit dysfunction.
Super-resolution imaging of active zones in dopamine axons. Rotating 3D view of bassoon (green, active zone marker) and TH (magenta, dopamine axon marker) from a 3D-SIM experiment in a dorsal striatal slice (10x10x2 μm3) showing volume-rendered raw images (1-10s), surface-rendered bassoon clusters and dopamine axons (10-17s) and bassoon clusters within dopamine axon.
Local Axonal Computation: Acetylcholine Triggers Dopamine Action Potentials
Information flow in neurons proceeds by integrating inputs in dendrites, generating action potentials in the soma and releasing neurotransmitters in the axon. We found that the activity of striatal cholinergic interneurons induces action potential firing in distal dopamine axons and broadcasts dopamine release. This mechanism bypasses the law of dynamic polarization of dendrite-soma-axon information flow, serves as a physiological regulation for striatal computation and contributes to behavior. Meanwhile, released dopamine strongly inhibits the activity of cholinergic neurons with high spatiotemporal precision. The purpose of this study is to understand the prevalence, physical basis, functional significance, and therapeutic potential of these reciprocal interactions.
Reference: Liu, et al. Science 2022
Spontaneous ACh-induced dopamine release in striatal slices. Example imaging and analyses of dopamine release (using DA sensor) in striatal slices (10 s, normal playback speed). A raw movie is shown on the left, the corresponding ΔF/F0 is shown in the middle, and detected dopamine release events are depicted on the right.
Acetylcholine induces ectopic firing in dopamine axons. Left, Schematic and example two-photon image of direct recording from dopamine axons. Synaptophysin-tdTomato was expressed by using mouse genetics in dopamine axons. The recorded axon was filled with Atto488 (green) through the recording pipette and puff pipette containing carbachol (acetylcholine receptor agonist) and Atto 488. Middle, Example responses of dopamine axon to current injections through the whole-cell pipette. Right, responses of the recorded dopamine axon to 10 consecutive carbachol puffs. Axonal action potentials were evoked using this stimulation.
From Distributed Striatal Activity to Quantitative Movement States
These movies connect large-scale neural recordings with AI-assisted behavioral analysis. Together, they show how distributed striatal population activity can be measured across space and aligned to precisely reconstructed natural movement.
Large-Scale Striatal Activity Across 16 Recording Sites
A multi-fiber photometry platform simultaneously monitors D1 medium spiny neuron activity across the striatum while the animal behaves freely. The synchronized traces and correlation structure reveal coordinated activity alongside regional heterogeneity, providing a systems-level view of how striatal populations participate in movement.
Synchronized Multi-View Tracking and 3D Movement Reconstruction
Six synchronized cameras capture behavior from complementary viewpoints. The views are integrated into a three-dimensional pose representation and aligned in time with concurrent fiber-photometry signals. This pipeline transforms complex natural behavior into interpretable movement states that can be mapped onto dopamine and striatal population dynamics.