Although learning in response to extrinsic reinforcement is theorized to be driven by dopamine signals that encode the difference between expected and experienced rewards, skills that enable verbal or musical expression can be learned without extrinsic reinforcement. Instead, spontaneous execution of these skills is thought to be intrinsically reinforcing. Whether dopamine signals similarly guide learning of these intrinsically reinforced behaviours is unknown. In juvenile zebra finches learning from an adult tutor, dopamine signalling in a song-specialized basal ganglia region is required for successful song copying, a spontaneous, intrinsically reinforced process. Here we show that dopamine dynamics in the song basal ganglia faithfully track the learned quality of juvenile song performance on a rendition-by-rendition basis. Furthermore, dopamine release in the basal ganglia is driven not only by inputs from midbrain dopamine neurons classically associated with reinforcement learning but also by song premotor inputs, which act by means of local cholinergic signalling to elevate dopamine during singing. Although both cholinergic and dopaminergic signalling are necessary for juvenile song learning, only dopamine tracks the learned quality of song performance. Therefore, dopamine dynamics in the basal ganglia encode performance quality during self-directed, long-term learning of natural behaviours.

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.

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.

Polycystic Ovary Syndrome (PCOS), affects 5-20% of women of reproductive age, it is the leading cause of anovulatory infertility accounting for 70-90% of cases and resulting in lower natural conception rates and a significant contributor to adverse pregnancy outcomes. Following PRISMA 2020 guidelines, this systematic review synthesized evidence from 2014-2025, evaluating the evolving landscape of PCOS pregnancy management. It explores the relationship between PCOS and reproductive outcomes, details specific maternal and perinatal complications, and discusses the latest evidence-based interventions and emerging therapies to improve pregnancy outcomes and the long-term health of both mother and child. The findings revealed that the syndrome's pathophysiology driven by hyperandrogenism, insulin resistance, and obesity significantly increases the risks of early pregnancy loss, gestational diabetes, and pre-eclampsia. There is a paradigm shift toward individualized, multidisciplinary care. Evidence-based strategies highlight the superiority of letrozole for ovulation induction, the metabolic benefits of metformin, and the necessity of nuanced lifestyle interventions over simple weight-loss models. Furthermore, emerging research into immune-metabolic pathways, such as Interleukin-22, suggests novel therapeutic directions. The review concludes that recognizing PCOS as a high-risk obstetric condition and integrating early metabolic screening into standard care are essential to improving maternal and neonatal outcomes.

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the gut, whose pathogenesis is closely related to immune dysregulation. Regulatory T cells (Tregs), as a key cell population maintaining intestinal immune tolerance, exhibit not only reduced frequency but, more critically, profound functional deficiencies, including the generation of pro-inflammatory ex-Tregs, and loss of lineage stability in the inflamed gut microenvironment of IBD. This review systematically delineates the sophisticated biological characteristics of Tregs, with a particular focus on the epigenetic and metabolic checkpoints that govern their stability. We critically summarize the aberrant changes of Tregs in IBD, emphasizing mechanisms such as inflammatory cytokine-induced Treg plasticity (e.g., Th1-like or Th17-like conversion) and microbiota-metabolite axis-mediated functional modulation. Furthermore, we provide an in-depth analysis of emerging therapeutic strategies aimed at restoring Treg suppressive capacity, including selective cytokine therapy (e.g., low-dose/engineered IL-2), adoptive transfer of engineered antigen-specific Tregs (including CAR-Tregs), microbiome/dietary interventions, and pharmacological modulation of Treg differentiation. We also discuss the disrupted crosstalk between Tregs and other innate and adaptive immune cells within the IBD milieu. Finally, this review highlights how cutting-edge technologies like single-cell multi-omics and spatial transcriptomics are delineating the heterogeneous landscape and uncovering novel, disease-specific Treg subpopulations, thereby paving the way for precise Treg-targeting therapies. Unlike previous reviews that broadly catalog Treg abnormalities, this review offers a refined conceptual framework centered on the critical distinction between lineage-defective ex-Tregs and exhausted effector Tregs (eTregs), and integrates recent multi-omics insights to redefine Treg functional failure in IBD.