Precisely timed dopamine signals establish distinct kinematic representations of skilled movements

Abstract

Brain dopamine is critical for normal motor control, as evidenced by its importance in Parkinson Disease and related disorders. Current hypotheses are that dopamine influences motor control by 'invigorating' movements and regulating motor learning. Most evidence for these aspects of dopamine function comes from simple tasks (e.g., lever pressing). Therefore, the influence of dopamine on motor skills requiring multi-joint coordination is unknown. To determine the effects of precisely-timed dopamine manipulations on the performance of a complex, finely coordinated dexterous skill, we optogenetically stimulated or inhibited midbrain dopamine neurons as rats performed a skilled reaching task. We 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.

Nucleus accumbens D1-receptors regulate and focus transitions to reward-seeking action

“…Notably, both optogenetic inhibition and stimulation of substantia nigra pars compacta dopamine cells or D1-expressing MSNs have been shown to disrupt ongoing movements (Bova et al, 2020;Tecuapetla, Jin, Lima, & Costa, 2016), which parallels the effect observed here that systemic administration of not just the D1R antagonist but also the D1R agonist slowed travel to the lever. The latter manipulation also caused a small but reliable increase in incorrect lever presses on Go trials, and both effects may reflect competition between different potential reward-associated instrumental responses in dorsal striatum (Bova et al, 2020).…”

Evolution of Gross Forelimb and Fine Digit Kinematics during Skilled Reaching Acquisition in Rats

“…The possible neural substrates for such variability are broad. One candidate is differences in dopamine signaling/receptor profiles, as dopamine plays an important role in motor adaptation ( Panigrahi et al, 2015 ; Bova et al, 2020 ). Other possibilities include differences in cortical plasticity ( Li et al, 2017 ; Hyland et al, 2019 ) and corticostriatal coherence ( Lemke et al, 2019 ).…”

“…Thus, coordinated corticostriatal activity could be correlated with changes in fine digit kinematics not evident from success rate. Indeed, previous work found that optogenetic manipulations of substantia nigra pars compacta dopamine neurons during skilled reaching disrupted the coordinated execution of digit movements with gross forelimb movements ( Bova et al, 2020 ). Therefore, basal ganglia circuitry does regulate some aspects of fine digit control, or at least its timing with respect to gross forelimb movements.…”

Dopamine neuron stimulation induces context-dependent abnormal involuntary movements in healthy rats

“…After rats completed training, we implanted an optical fiber over SNc contralateral to the rat's preferred reaching paw. Opsin expression was restricted to TH-expressing neurons in SNc projecting to striatum, and nigrostriatal TH expression was preserved (Figure S1, Bova et al, 2020).…”

“…In addition to differences in AIMs between ''reaching'' and ''non-reaching'' epochs, ''non-reaching'' AIMs were more severe with inter-reach than during-reach stimulation (Figure 3D). This is despite the fact that the duration of stimulation was similar for both groups, with a median during-reach stimulation duration of 5.37 s and a median inter-reach stimulation duration of 5 s (Bova et al, 2020). This suggests two (D) A single skilled reaching trial.…”