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.

To understand the neural basis of behavior, it is necessary to record brain activity in freely moving animals. Advances in implantable multi-electrode array technology have enabled researchers to record the activity of neuronal ensembles from multiple brain regions. The full potential of this approach is currently limited by reliance on cable tethers, with bundles of wires connecting the implanted electrodes to the data acquisition system while impeding the natural behavior of the animal. To overcome these limitations, here we introduce a multi-channel wireless headstage system designed for small animals such as rats and mice. A variety of single unit and local field potential signals were recorded from the dorsal striatum and substantia nigra in mice and the ventral striatum and prefrontal cortex simultaneously in rats. This wireless system could be interfaced with commercially available data acquisition systems, and the signals obtained were comparable in quality to those acquired using cable tethers. On account of its small size, light weight, and rechargeable battery, this wireless headstage system is suitable for studying the neural basis of natural behavior, eliminating the need for wires, commutators, and other limitations associated with traditional tethered recording systems.

A_2Areceptors are a major class of G-protein-coupled receptors for adenosine. Highly expressed in the striatum, on the projection neurons giving rise to the striatopallidal or “indirect” pathway, they have been implicated in sleep, addiction, and other processes, yet their role in the control of striatal circuits and behavior remains unclear. Using established assays from the instrumental learning paradigm, we showed that mice with striatum-specific deletion of A_2Areceptors were selectively impaired in habit formation. After training that generated habitual lever pressing in wild-type controls, the performance of striatum-specific A_2Aknock-out mice remained goal directed, being highly sensitive to outcome devaluation and reversal of the action–outcome contingency. These data demonstrate a critical role for A_2Areceptors on striatopallidal medium spiny projection neurons in shaping behavior and decision making, providing the first instance of a selective alteration in instrumental learning after striatum-specific genetic manipulations.

Central to the production of adaptive behavior is the ability to learn the temporal order of behavioral elements (e.g., A, B, C). Yet little is known about neural substrates of serial order in self-initiated behavioral sequences. The present study assessed the contributions of specific dorsal striatal regions to the acquisition of serial order in mice, using a two-action sequence task without instructive cues. Excitotoxic lesions of the sensorimotor (dorsolateral) striatum dramatically impaired the acquisition of a simple sequence; in contrast, lesions of the associative (dorsomedial) striatum had no significant effect. Neither lesion caused gross motor impairments or affected the learning of nonsequential actions. These results demonstrate for the first time a critical role of the sensorimotor striatum in the learning of serial order.