Dual neuromodulatory dynamics underlie birdsong learning.
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.
Vibrissa-based object localization in head-fixed mice.
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.
Ih Shapes Pathway-Specific Inhibition in Substantia Nigra Pars Reticulata.
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.
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Basal Ganglia Advances
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.
Progress in Voltage Imaging
Recent advances in the field of Voltage Imaging, with a special focus on new constructs and novel implementations.
Navigation & Localization
Work related to place tuning, spatial navigation, orientation and direction. Mainly includes articles on connectivity in the hippocampus, retrosplenial cortex, and related areas.
Most Popular Recent Articles
Effects of mindfulness-based intervention on teachers' work stress: A systematic review and meta-analysis of randomized controlled trials.
BackgroundIn recent years, the increasing demand for educational innovation and quality has created multiple occupational stressors for teachers. Long-term exposure to these stressors increases the risk of burnout, which influences mental and public health. Although numerous studies have evaluated the effectiveness of stress reduction interventions for educators, a gap exists in evidence-based research on mindfulness-based interventions (MBIs), specifically targeting this professional group.ObjectsThis study aims to evaluate the overall effects of MBIs on teachers' work stress.MethodsThis systematic review and meta-analysis focused on randomized controlled trials (RCTs) to evaluate the effectiveness of MBIs in alleviating teachers' work-related stress. Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines, we searched five databases (PubMed, EMBASE, Cochrane, Web of Science, and PsycINFO) for relevant RCTs up to July 2025. We assessed the risk of bias using Cochrane RoB 2 tool.ResultsPooled data from 13 trials (N = 2119) showed that, compared with the waitlist control group, perceived stress significantly decreased after intervention (standardized mean difference, SMD = -2.37, 95% CI = [-4.40, -0.35]. Additionally, mindfulness levels increased (SMD = 0.59, 95% CI = [0.39, 0.79], p < 0.001), and negative emotions decreased (SMD = -0.95, 95% CI = [-1.27, -0.62], p < 0.001). However, the presence of methodological and clinical heterogeneity requires a cautious interpretation of these results.ConclusionFindings suggest that MBIs serves as an effective tool for reducing general perceived stress and improving teacher well-being. Results also emphasize the need to design and conduct studies with long-term follow-up.
Engineering a Natural Ferritin Nanozyme-Probiotic Biosynthesis System for Inflammatory Bowel Disease Therapy.
With the increasing incidence of inflammatory bowel disease (IBD), antioxidant therapies aimed at scavenging excess reactive oxygen species (ROS) are considered promising treatment options. However, current strategies, such as the use of natural antioxidants or synthetic nanozymes, are often limited by inefficient biological delivery and potential safety concerns. To address these challenges, we developed OFn-EcN (OmpA-Ferritin nanozymes expressed in EcN), a novel biosynthetic system that integrates natural ferritin nanozymes with the beneficial probiotic (EcN). Specifically, biosynthesized ferritin nanozymes exhibit superoxide dismutase- and catalase-like activities to scavenge ROS in a cascade. Upon oral administration, OFn-EcN effectively neutralizes excessive ROS in the gut, protecting against probiotics and breaking the vicious cycle of inflammation and oxidative damage. Furthermore, the system restores intestinal barrier integrity, enhances nutrient absorption, and reestablishes a healthy microbial balance with a low risk of extraintestinal dissemination and high biosafety. In preclinical models, OFn-EcN effectively prevented the onset of DSS-induced colitis. Thus, this innovative approach offers a promising strategy for the prevention and effective alleviation of IBD.
Molecular Evolution of Organic Matter Humification Governs Ferrihydrite Transformation: Interfacial Electron Transfer Mechanisms and Carbon Preservation Implications.
During soil humification, organic matter (OM) develops distinct compositional and chemical signatures across the progressive stages. However, how these evolving OM characteristics influence iron (hydr)oxide transformation and ultimately regulate carbon preservation remains unclear. Through controlled anaerobic incubation experiments with ferrihydrite (Fh) and straw-derived OM from sequential soil humification stages under Fe(II)-mediated conditions, we found that advancing humification increasingly inhibited Fh crystallization, reducing its transformation to lepidocrocite/goethite from 45.3% in the degradation stage to 21.5% in the maturation stage. This stage-dependent inhibition correlated strongly with the accumulation of highly unsaturated and phenolic compounds (HUPs), which disrupted interfacial electron transfer and mineral nucleation, which are key processes in secondary mineral formation. Mechanistically, HUPs facilitated ternary Fh-OM-Fe(II) complex formation via the C-O-Fe bond, enhancing Fe(II) adsorption while narrowing the Fe(II)-Fh redox potential gap to suppress interfacial electron transfer. Furthermore, HUPs reduced the mineral surface potential and impeded particle agglomeration, thereby disrupting the crystallization of nucleation precursors. Consequently, the inhibited Fh transformation facilitated the selective adsorption of HUPs and their molecular conversion to condensed aromatics, thereby preferentially preserving organic carbon from advanced humification stages. These findings highlight the stage-dependent regulation of Fh transformation by humified OM and its implication for carbon preservation, advancing our understanding of coupled carbon-iron biogeochemistry in soils.