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.

Per- and polyfluoroalkyl substances (PFAS) are called forever chemicals due to the extremely stable C─F bond (bond energy of 485 kJ·mol), which leads the persistent existence in the natural environment thus poses a threat to human health. Compared with simple removal without destruction, defluorination is a more meaningful and thorough way for the harmless disposal of PFAS. In this review, the relationship between the structural properties of PFAS and defluorination mechanism are concluded. Thereafter, we discussed the advantages and limitations of defluorination techniques and specific defluorination pathways of active substances (free radicals and electron). This will provide a comprehensive theoretical foundation for the selection and improvement of defluorination technologies. The influence of key factors on the practical application of defluorination technologies in wastewater treatment plants are assessed in detail from the perspectives of reaction solvents, homogeneous and heterogeneous systems, and reactor design. Importantly, the pilot-scale application of relevant PFAS defluorination technologies has also been discussed. Finally, we prospect for the future research direction of PFAS defluorination from the aspects of precise exploration of reaction pathways, fluorine balance, resource recovery, and life cycle assessment (LCA). This will provide a practical strategy for addressing the urgent issue of PFAS-contaminated wastewater.

Targeting disease-specific chemical signals enables precise therapeutic control over complex pathologies. In Alzheimer's disease (AD), elevated hydrogen peroxide (HO) accompanies hallmark features, including amyloid-β (Aβ) aggregate deposition and metal ion dyshomeostasis, creating an oxidative milieu primed for selective chemical activation. Here, we show a rationally designed prodrug platform that harnesses HO as an endogenous trigger for redox-based therapy. Boronic ester-masked precursors (BE-1 and BE-2) remain inert under physiological conditions but undergo rapid oxidative deboronation in the presence of HO, releasing redox-active aminophenols. These activated molecules exhibit multimodal pathological modulation, as revealed by molecular-level biochemical and biophysical analyses: scavenging reactive oxygen species, inducing residue-specific oxidative modifications of Aβ, and redirecting aggregation pathways of both metal-free and metal-bound Aβ. In AD transgenic mice, BE-1 undergoes conversion to its active form within the brain tissue. Long-term administration of BE-1 markedly reduces hippocampal oxidative stress, lowers amyloid plaque burden, and improves cognitive performance. This pathology-responsive, activity-based prodrug strategy provides a chemically precise framework for simultaneously modulating multiple, interconnected drivers of neurodegeneration.

The rapid advancement of perovskite solar cells (PSCs) through high-power conversion efficiencies (PCEs) and low fabrication costs made them a potential candidate for the next generation of photovoltaic technology. Although, the inverted (p-i-n) configuration of the PSCs has recently gained attention due to low temperature production, the regular (n-i-p) architecture remains a benchmark model for inorganic HTLs due to high PCEs and well characterized interfacial energy levels. Hole transport layer plays a vital role in extracting photogenerated holes and minimizing charge recombination and energy losses in n-i-p architecture. While organic materials like spiro-OMeTAD have dominated HTL research, their limitations in stability, cost, environmental sustainability, and scalability have steered interest in inorganic alternatives. This comprehensive review systematically explores recently progress in inorganic HTLs for n-i-p PSCs, focusing on metal oxides, metal chalcogenides and emerging inorganic compounds. Important aspects of the HTLs required for enhancing the PSCs, including optical properties, energy gap, band alignment, deposition techniques and interfacial engineering strategies with emphasis on their influence on PCEs, stability and commercial viability is carried out. By consolidating recent advancements and identifying remaining key challenges, this review offers a critical foundation for advancing the design and optimization of efficient, stable and scalable n-i-p PSCs.