Precisely timed dopamine signals establish distinct kinematic representations of skilled movements

Title: Precisely timed dopamine signals establish distinct kinematic representations of skilled movements

Journal: eLife (2020) ;9:e61591

Link: https://elifesciences.org/articles/61591

Comments:

The goal of this study was to determine the effects of precisely timed dopaminergic manipulations on a complex, finely coordinated, and relatively unconstrained motor skill. To do this, they optogenetically stimulated or inhibited midbrain dopamine neurons as rats performed a skilled reaching task. In skilled reaching, rats learn the coordinated forelimb and digit movements to reach for, grasp and consume sugar pellets.

By combining skilled reaching, optogenetics, and measurement of three-dimensional paw/digit kinematics, they addressed the following questions. First, they asked whether dopamine manipulations affect current or subsequent reaches. Second, they asked how reach kinematics – specifically coordination between forelimb and digit movements – are influenced by dopamine manipulations.

They found that reach kinematics and coordination between gross and fine movements progressively changed with repeated manipulations. However, once established, rats transitioned abruptly between aberrant and baseline reach kinematics in a dopamine-dependent manner. These results suggest that precisely timed dopamine signals have immediate and long-term influences on motor skill performance, distinct from simply ‘invigorating’ movement. This phenomenon has clinical analogy with rapid motor fluctuations in PD patients.

Their dopamine manipulations influenced ‘vigor’ in unexpected ways: dopamine neuron stimulation decreased, and inhibition increased, movement amplitude (reach extent). Furthermore, both stimulation and inhibition decreased movement speed. These effects apparently contradict previous work directly correlating dopaminergic tone with movement velocity and/or amplitude. This discrepancy may be due to different demands on the motor system.

Within a ‘vigor’ framework, dopamine may invigorate the next submovement at the expense of the current one, compressing the overall sequence. In the limiting case, overlapping submovements could manifest as muscle co-contractions and dystonia, a possibility supported by the rare occurrence of abnormal movements intruding into reaches in the most severely affected rats.