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Authors & Affiliations
Teris, Wing Kin Tam, Rasha Elghaba, Kouichi Nakamura, Julien Carponcy, Guy Yona, Peter J. Magill
Abstract
The striatum intricately regulates motor and cognitive functions through the dynamic interplay of dopamine (DA), acetylcholine (ACh), and intrinsic neuronal firing, bearing profound implications for disorders like Parkinson's. However, the interaction between striatal DA and ACh, and their collective impact on striatal neuron activity in health and disease, are not fully understood. This study aims to elucidate the complex interplay between ACh, DA, and neuronal activity in the striatum during sensory and motor events. Utilizing a specialized Delayed-Go reaching task for head-fixed mice, we recorded real-time DA and ACh fluctuations using genetically-encoded sensors and fibre photometry. In some mice, we also simultaneously monitored striatal neural activity with Neuropixels probes. Our task design allows for the separation of cue, movement, and reward responses in time, shedding light on the interactions between neuromodulators and neuronal activity during different task events. Photometry results indicated a dynamic interplay between ACh and DA signals, characterized by occasional alignment and opposing patterns, which in turn implies a complex, time-locked interaction during specific task-related events. Employing dynamic time warping and hierarchical clustering of neuronal response curves, our Neuropixels data unveiled a rich repertoire of distinct activity motifs among groups of striatal neurons. These motifs tend to segregate spatially, suggesting distinct event-related responses in different regions of the striatum. Our findings offer new insights into the complexity of neuromodulator signalling and neuronal activity in striatum.