Objective: To develop a new behavioral task for assessment of mice forelimb movements, and evaluate the substantia nigra pars compacta dopaminergic cells’ (SNpc) correlates of movement kinematics.

Background: Models of basal ganglia function frequently focus on initiation deficits. This contrasts with what is observed in Parkinson’s Disease (PD) where chronic dopamine depletion is associated not only with “slowness of initiation” but also with “progressive reduction in speed and amplitude of repetitive actions” (Bradykinesia). The role of basal ganglia on movement speed and amplitude remains unclarified, but it seems reasonable to hypothesize that dopamine has a pivotal role.

Methods: Repetitive finger tapping is commonly used to assess movement speed and amplitude in PD. Using this as an inspiration we developed a novel self-paced operant task, in which mice learn to perform a particular sequence of actions, using only one forelimb. The task was designed to collect data regarding the spatial position, speed and acceleration of the forelimb of the mouse. A miniature epifluorescence microscope (~1.9g) was used to image GCaMP6f fluorescence (a calcium indicator) in dopaminergic SNpc cells while TH-cre mice performed the task. After animals learned the task we induced partial dopamine depletion by unilateral intrastriatal 6-Hydroxydopamine injection.

Results: Preliminary results showed that after depletion there is a redistribution of movement speed with an increase in slower movements and with longer within-sequence inter-press intervals. We also found changes in the sequence microstructure, including the number of lever presses/sequence.

Using in vivo calcium imaging we identified phasic activity of SNpc dopaminergic accompanying the start of a learned lever-press sequence both in healthy and partially dopamine depleted animals.

Conclusions: We developed a clinically-relevant task for movement sequence kinematics assessment in mice, and identified SNpc correlates of movement. Ongoing analysis using the combination of these 2 tools will allow us to clarify the role of SNpc dopaminergic neurons in different type of movements (slow vs. fast movements), in healthy and chronic dopamine depleted mice. This will have impact in our comprehension on the role of basal ganglia dysfunction in PD symptoms.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neural-correlates-of-movement-sequence-kinematics-in-substantia-nigra-dopaminergic-cells/