NEURAL ACTIVITY MOTIFS AND DOPAMINE-ACETYLCHOLINE DYNAMICS IN THE STRIATUM: INSIGHTS FROM A MOUSE DELAYED-GO REACHING TASK

The striatum is a key brain region involved in coordinating motor and cognitive functions, with the neuromodulators dopamine (DA) and acetylcholine (ACh) playing central roles in organising striatal activity through their intricate interactions. These neuromodulator dynamics are essential for normal brain function and are strongly implicated in neurological disorders such as Parkinson’s. However, the ways in which DA and ACh relate in time and influence each other, as well as how their interplay shapes striatal neuronal activity in both healthy and diseased states, are still not fully understood.
In this study, we set out to investigate this complexity by examining the relationship between DA, ACh, and striatal neuron firing during sensorimotor behaviour. We employed a Delayed-Go reaching task designed for head-fixed mice, which allowed us to temporally separate cue, movement, and reward components. During task performance, we recorded real-time fluctuations in DA and ACh using fibre photometry, while simultaneously capturing striatal neuron firing with high-density Neuropixels probes.
This approach enabled us to track how neuromodulator signals and neuronal activity co-evolve across distinct behavioural epochs. Using dynamic time-warping and hierarchical clustering, we identified a diverse set of neuronal activity response motifs within the striatum. These motifs exhibited spatial localization, suggesting region-specific processing dynamics. Furthermore, their correlations with DA and ACh signals varied across cue, movement, and reward phases, suggesting the involvement of distinct underlying neural circuits during different behavioural events.