Beyond reward prediction errors: the role of dopamine in movement kinematics

Abstract

We recorded activity of dopamine (DA) neurons in the substantia nigra pars compacta in unrestrained mice while monitoring their movements with video tracking. Our approach allows an unbiased examination of the continuous relationship between single unit activity and behavior. Although DA neurons show characteristic burst firing following cue or reward presentation, as previously reported, their activity can be explained by the representation of actual movement kinematics. Unlike neighboring pars reticulata GABAergic output neurons, which can represent vector components of position, DA neurons represent vector components of velocity or acceleration. We found neurons related to movements in four directions—up, down, left, right. For horizontal movements, there is significant lateralization of neurons: the left nigra contains more rightward neurons, whereas the right nigra contains more leftward neurons. The relationship between DA activity and movement kinematics was found on both appetitive trials using sucrose and aversive trials using air puff, showing that these neurons belong to a velocity control circuit that can be used for any number of purposes, whether to seek reward or to avoid harm. In support of this conclusion, mimicry of the phasic activation of DA neurons with selective optogenetic stimulation could also generate movements. Contrary to the popular hypothesis that DA neurons encode reward prediction errors, our results suggest that nigrostriatal DA plays an essential role in controlling the kinematics of voluntary movements. We hypothesize that DA signaling implements gain adjustment for adaptive transition control, and describe a new model of the basal ganglia (BG) in which DA functions to adjust the gain of the transition controller. This model has significant implications for our understanding of movement disorders implicating DA and the BG.

Axial levodopa-induced dyskinesias and neuronal activity in the dorsal striatum

“…Prior work demonstrates that striatal MSNs and FSIs encode aspects of movement (Berke et al, 2004; Berke, 2008; Hernandez et al, 2013; Jin et al, 2014; Barter et al, 2015a, 2015b). To examine striatal function during dyskinesias, we recorded striatal neuronal ensembles and tracked movement.…”

“…Previous studies have largely relied on AIM scores, which can be laborious and temporally limited (Lundblad et al, 2004). Tracking techniques have been used to correlate movements with striatal neurophysiology (Barter et al, 2015a, 2015b), and here we extend this work to LIDs.…”

Dynamic Nigrostriatal Dopamine Biases Action Selection

“…Under different experimental settings, nigrostriatal dopamine neurons have been suggested to encode the salience of stimuli (Matsumoto and Hikosaka, 2009), the value of cues in stimulus-response behavior (Kim et al, 2015; Morris et al, 2006), the initiation and termination of self-paced action sequences (Jin and Costa, 2010), and might even directly reflect movement kinematics (Barter et al, 2015). In the current study, mice were trained to dynamically select two alternative actions according to internally-monitored temporal information.…”

“…Indeed, recent studies with optical imaging have revealed that dopamine sends both reward- and movement-related information to the striatum, likely by different dopaminergic axons (Howe and Dombeck, 2016; Parker et al, 2016). Importantly, it has been further demonstrated that the movement-related signaling in dopaminergic axons is not only associated with but also capable of directly triggering movements, emphasizing a motor nature of the nigrostriatal dopamine system (Barter et al, 2015; Howe and Dombeck, 2016; Jin and Costa, 2010). Together with the current study, these results support functionally heterogeneous roles of dopamine signaling during behavior (Hamid et al, 2016; Kim et al, 2015; Schultz, 2007), acting at both fast and slow timescales (Hamid et al, 2016; Schultz, 2007).…”

Representation of spontaneous movement by dopaminergic neurons is cell-type selective and disrupted in parkinsonism

“…For example, some dopaminergic neurons respond to novel or salient events or during cognitive processes such as decision making and working memory (6,(8)(9)(10). Moreover, although the firing of these dopaminergic neurons generally has been thought not to vary consistently with movement (3,11), there is evidence that the activity of putatively classified dopaminergic neurons can change during movement execution in a heterogeneous manner (12)(13)(14)(15)(16). This evidence, in turn, raises the possibilities that at least some types of movement might be differentially encoded by the firing of distinct populations of dopaminergic neuron and that dysregulation of such activity might contribute to motor impairment in PD before, or commensurate with, frank neurodegeneration.…”