Final Report Summary - NEURALCHUNK (Neural bases of action chunking in basal ganglia subcircuits)
Our findings transformed the view of how cortico-basal ganglia circuits, affected in disorders like Parkinson’s and Huntington’s disease, operate during movement and learning. The basal ganglia were thought to facilitate movement by activation of the direct pathway (Go, prokinetic) and inhibition of the indirect pathway (No-Go, antikinetic). We developed novel approaches, including fiber photometry, to show that: both direct- and indirect striatal neurons are active during movement, this activity is action-specific, and necessary for movement. Furthermore, we uncovered that transient input from dopaminergic neurons (DANs) to striatum is critical for movement. DANs were thought to mainly encode reward-prediction errors. However, these neurons die in Parkinson’s leading to movement problems. We demonstrated DAN heterogeneity by showing that a DAN population in the substantia nigra (different than reward-encoding DANs) is active before movement, and critical for initiating and invigorating future movement. Our findings indicate that the striatum receives signals about what actions to do from sensorimotor cortices, and about the value/motivation to perform those movements from dopamine neurons; and selects which movements to execute in a given context by disinhibiting specific brainstem and cortical populations, via segregated projections from basal ganglia output.