Linking activity in specific cell types with perception, cognition, and action, requires quantitative behavioral experiments in genetic model systems such as the mouse. In head-fixed primates, the combination of precise stimulus control, monitoring of motor output, and physiological recordings over large numbers of trials are the foundation on which many conceptually rich and quantitative studies have been built. Choice-based, quantitative behavioral paradigms for head-fixed mice have not been described previously. Here, we report a somatosensory absolute object localization task for head-fixed mice. Mice actively used their mystacial vibrissae (whiskers) to sense the location of a vertical pole presented to one side of the head and reported with licking whether the pole was in a target (go) or a distracter (no-go) location. Mice performed hundreds of trials with high performance (>90% correct) and localized to <0.95 mm (<6 degrees of azimuthal angle). Learning occurred over 1-2 weeks and was observed both within and across sessions. Mice could perform object localization with single whiskers. Silencing barrel cortex abolished performance to chance levels. We measured whisker movement and shape for thousands of trials. Mice moved their whiskers in a highly directed, asymmetric manner, focusing on the target location. Translation of the base of the whiskers along the face contributed substantially to whisker movements. Mice tended to maximize contact with the go (rewarded) stimulus while minimizing contact with the no-go stimulus. We conjecture that this may amplify differences in evoked neural activity between trial types.

The substantia nigra pars reticulata (SNr) functions as the principal inhibitory output of the basal ganglia, with the timing of its spikes critically controlling downstream disinhibition required for movement initiation. The external globus pallidus (GPe) and D1-expressing medium spiny neurons (D1-MSNs) in the striatum provide GABAergic inputs to the SNr that differ in their amplitude and kinetic properties. How these inputs interact with the intrinsic membrane currents that determine SNr firing is only partially understood. Using optogenetics, computational modeling, and electrophysiology in acute mouse brain slices, 47 animals of either sex were used for measurements, and we found an unexpected interaction between GABAergic inputs and hyperpolarization-activated currents (Ih) that tunes inhibitory efficacy in a pathway-specific manner. GPe inputs evoke fast, large IPSCs that transiently suppress SNr firing within a narrow window but whose rapid decay enables depolarization from Ih to restore firing after only a brief pause. In contrast, the slower decay kinetics of striatal IPSCs enables more sustained inhibition that counters the depolarizing drive from Ih to produce longer pauses, despite their lower conductance amplitudes. Pharmacological blockade of Ih with ZD7288 eliminated the rapid recovery of firing after GPe inhibition and equalized the inhibitory efficacy between GPe and striatal pathways. These findings establish an important interplay between synaptic kinetics and intrinsic membrane conductances in establishing pathway-specific inhibitory balance in the basal ganglia. Our study reveals that inhibitory pathways to the substantia nigra pars reticulata are differentially shaped by the interplay between synaptic kinetics and intrinsic membrane conductances. Using optogenetics, electrophysiology, and modeling, we showed that fast-decaying GABAergic inputs from the external globus pallidus are rapidly overcome by Ih, producing only brief pauses in SNr firing, whereas slower striatal inputs generate longer-lasting inhibition. Blocking Ih abolishes this difference, demonstrating that intrinsic currents tune inhibitory efficacy in a pathway-specific manner. These results identify a biophysical mechanism that helps set the balance of basal ganglia output essential for movement control.

Frontal Cortex (FC) plays a pivotal role in adaptively controlling actions and their dynamics in response to incoming sensory signals. We explored FC encoding of identical stimuli and their behavioral consequences when they signified diametrically opposite responses depending on task context. Two groups of female ferrets performed Go-NoGo auditory categorization tasks with opposite contingencies and rewards, and diverse stimuli. Remarkably, despite opposite stimulus-action associations, single-unit responses were similar across all tasks, being more sustained and stronger to Target sounds (signaling a change in action) than to Reference sounds (indicating maintenance of ongoing actions) especially during task engagement. Overall activity was composed of three distinct dynamic response profiles. Each corresponded to a separate neuronal cluster and exhibited a different role in relation to the succession of task events. Decoding based on the temporal structure of population responses revealed distinct decoders that were aligned to different task events. Similar to single unit findings, the β-band power extracted from the FC local field potentials (LFPs) was strongly and similarly modulated during Target stimuli across all tasks despite opposite behavioral actions. In contrast, power in all other LFP frequency bands varied significantly across task stimuli and actions. Based on these findings, we propose the FC encodes a common, highly abstract representation of all the different behavioral tasks. We further outline a hypothetical model of pathway-specific functional projections from the tripartite FC neuronal clusters to the basal ganglia, consistent with previous evidence for the conjoint roles of the FC and striatum in adaptive motor control. The frontal cortex (FC) encodes an abstract representation of perception and action with associated rewards and cognitive functions. Thus, even when ferrets perform opposite Go/NoGo behaviors, FC responses exhibit similar sequences of dynamic patterns from 3 cell clusters. The first component is phasic encoding stimulus category and the decision to maintain or change ongoing actions. The second is a rapid response suppression, initiated if the animal switches to a new action. The third is a buildup of excitatory activity as the animal sustains its new action. We propose a model for how such an abstract FC representation may emerge from separate functional projections from the FC clusters to the striatum, offering new insights into the FC role in behavioral control.

Basal Ganglia Advances is a collection highlighting research on the structure, function, and disorders of the basal ganglia. It features studies spanning neuroscience, clinical insights, and computational models, serving as a hub for advances in movement, cognition, and behavior.

Recent advances in the field of Voltage Imaging, with a special focus on new constructs and novel implementations.

Work related to place tuning, spatial navigation, orientation and direction. Mainly includes articles on connectivity in the hippocampus, retrosplenial cortex, and related areas.

How the brain signals prediction errors for non-rewarding, yet significant, sensory events remains a central question. Although the cortical mismatch negativity provides a well-known signature for deviance detection, the contribution of subcortical dopamine remains unclear. This study tested the hypothesis that phasic dopamine in the nucleus accumbens encodes the salience associated with the violation of an ongoing statistical regularity. Using fiber photometry in freely moving rats, we contrasted an auditory oddball paradigm with a many-standards control. Deviant stimuli elicited a significantly amplified dopamine response compared with standard stimuli. Crucially, this dopamine response enhancement was absent in the control condition, demonstrating that the nucleus accumbens dopamine responds specifically to rule violation rather than mere stimulus rarity. The long latency of this signal (~500 ms) relative to the cortical mismatch negativity argues against a direct role in the initial detection of deviance. Instead, our findings support a model in which subcortical dopamine acts as a distinct salience signal, operating in parallel with cortical deviance detection, to evaluate unexpected events and guide subsequent behavioral adjustments.

Making appropriate decisions relies on the brain's capacity to evaluate the expected outcomes of available options and select the most rewarding action. The ventral striatum and midbrain dopamine neurons have been implicated in the option valuation process, consistent with the brain's reinforcement learning theory in which these brain structures encode and update value representations of expected outcomes. Extending beyond this framework, we found that the dopamine-ventral striatum system plays a more proactive role in action selection. We recorded single-unit activity from ventral striatum neurons in macaque monkeys as they sequentially evaluated an option, decided whether to perform an action to choose it, and expressed that motor action. The activity of these neurons initially reflected the value of the option but gradually shifted to reflect monkey's action selection, as if the ventral striatum translates the value information into the action. Moreover, optogenetic facilitation of dopamine input to the ventral striatum as well as electrical stimulation of this region altered monkey's action selection. Our findings reveal a previously unappreciated function of the ventral striatum as a neural hub that bridges option valuation and action selection, and demonstrate the contribution of dopamine in the process leading to action selection within this region.

Midbrain dopamine neurons promote reinforcement learning and movement vigor. An outstanding question is how dopamine-recipient neurons in the striatum parse these heterogeneous signals. Previous work suggests that cholinergic striatal interneurons may gate dopamine-dependent plasticity, but this has not been tested in behaving animals. Here we studied rats performing a decision-making task with reward-related and movement-related events. Optical measurement of dopamine and acetylcholine release in the dorsomedial striatum (DMS) revealed that reward cues evoked cholinergic pauses with different phase relationships relative to dopamine. When dopamine lagged cholinergic dips, dopamine predicted future behavior and DMS firing rates on subsequent trials. In contrast, when dopamine preceded cholinergic dips, there was no observable relationship between dopamine and learning. Finally, when dopamine was coincident with cholinergic bursts, it preceded and predicted the vigor of contralateral orienting movements. Our findings suggest that cholinergic dynamics determine whether dopamine promotes vigor or learning, depending on the instantaneous behavioral context.