Salient cues can prompt the rapid interruption of planned actions. It has been proposed that fast, reactive behavioral inhibition involves specific basal ganglia pathways, and we tested this by comparing activity in multiple rat basal ganglia structures during performance of a stop-signal task. Subthalamic nucleus (STN) neurons showed low-latency responses to Stop cues, irrespective of whether actions were successfully canceled or not. By contrast, neurons downstream in the substantia nigra pars reticulata (SNr) responded to Stop cues only in trials with successful cancellation. Recordings and simulations together indicate that this sensorimotor gating arises from the relative timing of two distinct inputs to neurons in the SNr dorsolateral “core” subregion: cue-related excitation from STN and movement-related inhibition from striatum. Our results support race models of action cancellation, with successful stopping requiring Stop cue information to be transmitted from STN to SNr before increased striatal input creates a point of no return.

The suppression of inappropriate actions is critical for flexible behavior. Cortical-basal ganglia networks provide key gating mechanisms for action suppression, yet the specific roles of neuronal subpopulations are poorly understood. Here, we examine Arkypallidal (“Arky”) and Prototypical (“Proto”) globus pallidus neurons during a Stop task, which requires abrupt cancellation of an imminent action. We first establish that Arky neurons can be identified by their firing properties across the natural sleep/wake cycle. We then show that Stop responses are earlier and stronger in the Arky, compared to the Proto, subpopulation. In contrast to other basal ganglia neurons, pallidal Stop responses are selective to Stop, rather than Go, cues. Furthermore, the timing of these Stop responses matches the suppression of developing striatal Go-related activity. Our results support a two-step model of action suppression: actions-in-preparation are first paused via a subthalamic-nigral pathway, then cancelled via Arky GABAergic projections to striatum.

SUMMARY Beta oscillations in cortical-basal ganglia (BG) circuits have been implicated in normal movement suppression and motor impairment in Parkinson’s disease. To dissect the functional correlates of these rhythms we compared neural activity during four distinct variants of a cued choice task in rats. Brief beta (~20 Hz) oscillations occurred simultaneously throughout the cortical-BG network, both spontaneously and at precise moments of task performance. Beta phase was rapidly reset in response to salient cues, yet increases in beta power were not rigidly linked to cues, movements, or movement suppression. Rather, beta power was enhanced after cues were used to determine motor output. We suggest that beta oscillations reflect a postdecision stabilized state of cortical-BG networks, which normally reduces interference from alternative potential actions. The abnormally strong beta seen in Parkinson’s Disease may reflect overstabilization of these networks, producing pathological persistence of the current motor state.

Fast-spiking interneurons (FSIs) can exert powerful control over striatal output, and deficits in this cell population have been observed in human patients with Tourette Syndrome and rodent models of dystonia. However, a direct experimental test of striatal FSI involvement in motor control has never been performed. We applied a novel pharmacological approach to examine the behavioral consequences of selective FSI suppression in mouse striatum. IEM-1460, an inhibitor of GluA2-lacking AMPARs, selectively blocked synaptic excitation of FSIs but not striatal projection neurons. Infusion of IEM-1460 into the sensorimotor striatum reduced the firing rate of FSIs but not other cell populations, and elicited robust dystonia-like impairments. These results provide direct evidence that hypofunction of striatal FSIs can produce movement abnormalities, and suggest that they may represent a novel therapeutic target for the treatment of hyperkinetic movement disorders.

Motor thalamus (Mthal) comprises the ventral anterior, ventral lateral, and ventral medial thalamic nuclei in rodents. This subcortical hub receives input from the basal ganglia (BG), cerebellum, and reticular thalamus in addition to connecting reciprocally with motor cortical regions. Despite the central location of Mthal, the mechanisms by which it influences movement remain unclear. To determine its role in generating ballistic, goal-directed movement, we recorded single-unit Mthal activity as male rats performed a two-alternative forced-choice task. A large population of Mthal neurons increased their firing briefly near movement initiation and could be segregated into functional groups based on their behavioral correlates. The activity of "initiation" units was more tightly locked to instructional cues than movement onset, did not predict which direction the rat would move, and was anticorrelated with reaction time (RT). Conversely, the activity of "execution" units was more tightly locked to movement onset than instructional cues, predicted which direction the rat would move, and was anticorrelated with both RT and movement time. These results suggest that Mthal influences choice RT performance in two stages: short latency, nonspecific action initiation followed by action selection/invigoration. We discuss the implications of these results for models of motor control incorporating BG and cerebellar circuits. Motor thalamus (Mthal) is a central node linking subcortical and cortical motor circuits, though its precise role in motor control is unclear. Here, we define distinct populations of Mthal neurons that either encode movement initiation, or both action selection and movement vigor. These results have important implications for understanding how basal ganglia, cerebellar, and motor cortical signals are integrated. Such an understanding is critical to defining the pathophysiology of a range of BG- and cerebellum-linked movement disorders, as well as refining pharmacologic and neuromodulatory approaches to their treatment.