Acetylcholine (ACh) release in the medial prefrontal cortex (mPFC) is a major contributor to the balance between attention and inhibitory control, which is crucial for the execution of adaptive goal-directed behaviors. Yet, our understanding of the functional heterogeneity within the mPFC, particularly how distinct cholinergic afferences and circuits regulate these processes, remains limited. Here, we used in vivo fiber photometry, neuronal tracing, and chemogenetics manipulations to demonstrate the role of the prelimbic sub-region of the mPFC (PrL) and its ascending cholinergic projections in a cued-Fixed Consecutive Number task (FCNcue task) in male mice. We found that following a transient activation at the initiation of the behavioral response (cue detection), persistent inhibition of PrL neuronal activity, measured by fiber photometry, may be necessary to maintain engagement in the task and completion of the chain of required responses (i.e., optimal responses). Moreover, we found that the PrL receives dense ACh projections almost exclusively from the most anterior-medial part of the basal forebrain (BF) comprising the horizontal and ventral parts of the diagonal band of Broca (HDB and VDB) and the substantia innominata (SI) nuclei. Finally, chemogenetic activation of this ACh pathway inhibited PrL activity and enhanced behavioral performance of the mice by increasing the percentage of optimal responses. Overall, this study provides insights into the spatial and temporal dynamics of cholinergic signaling to the PrL and its causal role on attentional control.

Midbrain dopamine (DA) neurons are diverse with distinct subpopulations being essential for key functions of the brain: nigrostriatal DA neurons for voluntary movement and mesolimbic DA neurons for learning from reward prediction errors. In addition to being primarily associated with distinct senso-motor or limbic cortical-striatal circuits, DA subpopulations also directly communicate with each other via local DA release in the midbrain. While the inhibitory synaptic nature of this dopamine-to-dopamine signaling has been well established, the pre- and postsynaptic identity and logic of connectivity among DA subpopulations are still unresolved. To fill this gap, we combined retrograde tracing with projection-specific optogenetic stimulation of DA neurons and patch-clamp recordings in the adult mouse of either sex. We functionally identified a unidirectional, motor-to-limbic design of the DA synapse in the midbrain. This motor-to-limbic negative feedback connection in the midbrain was independently confirmed by monosynaptic rabies tracing of projection-defined DA subpopulations. This DA synapse might complement the limbic-to-motor striato-nigro-striatal feedforward architecture of the basal ganglia. We identified the pre- and postsynaptic partners of the dopamine-to-dopamine synapse in the midbrain, independently by functional in vitro patch clamp recordings and monosynaptic rabies tracing of identified dopamine subpopulations. This DA synapse is surprisingly circuit-specific with presynaptic DA neurons projecting to the dorsal striatum and post-synaptic DA neurons projecting to the lateral shell of the nucleus accumbens. Thus, this DA synapse establishes a unidirectional, direct communication between the nigro-striatal and the meso-limbic dopamine systems.

The GABAergic striatal outputs forming the direct and indirect pathways of the basal ganglia (BG), classically defined by Drd1 and Drd2 expression, respectively, are crucial in the control of voluntary movement. Recent evidence has identified parallel direct and indirect pathways within striosomes, that exert opposing control over striatal DA release and thereby influencing locomotor behavior. These findings refine our understanding of how discrete BG pathways coordinate voluntary actions.

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.

Somatostatin-expressing low-threshold spiking interneurons (SOM-INs) constitute a key inhibitory population in the dorsal striatum, yet their contribution to parkinsonian states and L-DOPA-induced dyskinesia (LID) remains poorly understood. Here, we combined in vivo behavioral assays, chemogenetics, and ex vivo electrophysiology to examine how nigrostriatal dopamine loss and dopaminergic therapy shape SOM-INs' activity and function. During LID, SOM-INs displayed increased c-Fos expression, revealing their recruitment during dyskinetic states. Patch-clamp recordings showed that SOM-INs in control mice fire tonically with characteristic abrupt pauses. While their firing patterns are preserved after dopamine depletion and L-DOPA therapy, dopamine depletion shifted their interspike interval distribution toward longer intervals, indicating reduced intrinsic activity. This deficit was partially reversed by chronic L-DOPA. Consistent with their expression of Drd1/Drd5 transcripts, SOM-INs were excited by the D1/D5 receptor agonist SKF81297 across groups. Chemogenetic inhibition experiments revealed a functional role for SOM-INs in early rotarod learning, demonstrating their contribution to motor skill acquisition, but did not affect baseline motor output in sham or parkinsonian mice. Moreover, SOM-IN inhibition during chronic L-DOPA treatment modestly but consistently exacerbated LID expression selectively during the wearing-off phase, without altering parkinsonian symptoms or the therapeutic efficacy of L-DOPA. Notably, SOM-IN inhibition did not modify the long-duration antiparkinsonian response that persisted after discontinuing L-DOPA. Together, these findings identify SOM-INs as an intrinsically active striatal interneuron population whose excitability is shaped by dopamine depletion and dopamine receptor stimulation, and whose activity restrains dyskinetic responses to dopaminergic overstimulation. Their selective influence on dyskinesia, but not on the therapeutic actions of L-DOPA, highlights SOM-INs as a potential target for circuit-level interventions aimed at improving the motor side-effect profile of dopaminergic therapies.

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.