SUB-SECOND STRIATAL DOPAMINE AND ACETYLCHOLINE SIGNALLING DYNAMICS DURING A DELAYED-GO REACHING TASK IN DOPAMINE-INTACT AND PARKINSONIAN MICE

Dopamine (DA) and acetylcholine (ACh) are key neuromodulators in the striatum, which serves as a critical hub for motor and cognitive information processing in the basal ganglia. Understanding DA and ACh release dynamics on short timescales is crucial for elucidating their impact on striatal function in health and in parkinsonian states. This study aimed to define sub-second DA and ACh dynamics in the dorsal striatum across cue, movement and reward phases of a Delayed-Go reaching task in both dopamine-intact and parkinsonian mice. During task performance by head-fixed mice, we recorded fluctuations of DA and ACh, readout by fluorescence changes of genetically-encoded sensors via fibre photometry, before and after 6-OHDA lesion of dopamine neurons. DA and ACh signals exhibited distinct, phasic changes around cue, movement, and reward delivery. These transients were modulated by different behavioural factors. In Parkinsonian mice, partial DA depletion disrupted normal DA and ACh signalling, with phase-specific alterations observed across the task structure. Our findings show that DA and ACh signals rapidly fluctuate in the dorsal striatum during goal-directed movement, and reveal how these signalling dynamics are altered in parkinsonian states. These insights deepen our understanding of striatal neuromodulation in both health and disease.