Abstract
Interplay between dopaminergic and cholinergic neuromodulation in the striatum is crucial for movement control, with prominent models proposing pro-kinetic and anti-kinetic effects of dopamine and acetylcholine release, respectively. However, the natural, movement-related signals of striatum cholinergic neurons and their relationship to simultaneous variations in dopamine signaling are unknown. Here, functional optical recordings in mice were used to establish rapid cholinergic signals in dorsal striatum during spontaneous movements. Bursts across the cholinergic population occurred at transitions between movement states and were marked by widespread network synchronization which diminished during sustained locomotion. Simultaneous cholinergic and dopaminergic recordings revealed distinct but coordinated sub-second signals, suggesting a new model where cholinergic population synchrony signals rapid changes in movement states while dopamine signals the drive to enact or sustain those states.
Highlights
IntroductionStriatum cholinergic interneurons (ChIs) have long been recognized as critical for normal functioning of the basal ganglia in the control of movement and in learning and responding to motivational and salient stimuli (Apicella et al, 1996; Apicella et al, 1997; Apicella et al, 1991; Collins et al, 2016; Kimura et al, 1984; Kondabolu et al, 2016; Schulz et al, 2011; Kaneko et al, 2000)
This clinical observation led to the hypothesis that loss of dopaminergic (DA) innervation to the dorsal striatum from the substantia nigra pars compacta (SNc) in Parkinson’s Disease (PD) disrupts a dynamic balance between acetylcholine and dopamine signaling (Barbeau, 1962)
These results demonstrate that transient dorsal striatum cholinergic interneurons (ChIs) population signals reflect rapid transitions in internally generated spontaneous movement, from rest to movement or during resets in locomotion, independently of changes in reward prediction or experimentally generated salient stimuli
Summary
Striatum cholinergic interneurons (ChIs) have long been recognized as critical for normal functioning of the basal ganglia in the control of movement and in learning and responding to motivational and salient stimuli (Apicella et al, 1996; Apicella et al, 1997; Apicella et al, 1991; Collins et al, 2016; Kimura et al, 1984; Kondabolu et al, 2016; Schulz et al, 2011; Kaneko et al, 2000). Bilateral optogenetic stimulation of dorsal striatum ChIs reduces gross spontaneous locomotion (Kondabolu et al, 2016) (an effect counter to stimulation of DA [Howe and Dombeck, 2016; da Silva et al, 2018]), while optogenetic inhibition can alleviate motor deficits of L-DOPA induced dyskinesias in rodent PD models (Bordia et al, 2016b; Maurice et al, 2015; Ztaou et al, 2016) These findings suggest that cholinergic signaling opposes the pro-kinetic actions of dopamine in the striatum.
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