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.

Experience of visceral pain occurs when there is discomfort originating from internal organs of the body, often resulting from injury, infection, inflammation, ischemia, tumors, or neuropathy. In clinical practice, visceral pain is recognized as one of the most prevalent and incapacitating types of pain. It encompasses a diverse range of conditions impacting organs within thoracic, pelvic, and abdominal regions. Specifically, visceral pain of abdominal origin often presents as diffuse and poorly defined sensations of varying intensities. This characteristic arises from relatively sparse sensory innervation of visceral organs and divergent nature of visceral inputs. In addition, visceral noxious stimuli differ significantly from somatic pain triggers. Perception of visceral noxious stimuli from abdominal organs starts with transduction of signals at peripheral processes of sensory neurons, and transmission of these impulses to cortical centers, processing pain. Pathways concerned with nociceptive signaling from abdomen include intricate meshwork of neurons interconnecting different functional loci within nervous system. This review brings together current concepts on how abdominal pain is processed at several interconnected levels. Understanding of physiological pathways involved in abdominal pain processing supplemented with history, physical examinations, necessary biochemical, histopathological and radiological investigations constitute the cornerstone for abdominal pain management in clinical settings.

Early identification of complicated acute appendicitis remains a clinical challenge. Serum bilirubin has been proposed as a potential biomarker reflecting disease severity rather than primary diagnosis. To evaluate the diagnostic accuracy of serum bilirubin in predicting complicated acute appendicitis using histopathology as the reference standard.

The biosynthesis of 3'-phosphoadenosine 5'-phosphosulfate (PAPS), a universal sulfate donor, is catalyzed by two isoenzymes: PAPS synthetase 1 (PAPSS1) and PAPS synthetase 2 (PAPSS2). While PAPSS1 is ubiquitously expressed, PAPSS2 shows tissue-specific expression and plays a key role in cartilage development and adrenal steroid metabolism. PAPSS2 deficiency impairs dehydroepiandrosterone sulfation (DHEA-S), leading to increased bioactive androgens and hyperandrogenism. Biallelic PAPSS2 variants cause skeletal dysplasias from brachyolmia (BO) to severe spondyloepimetaphyseal dysplasia (SEMD). This study aimed to expand the PAPSS2 mutational spectrum and explore potential genotype-phenotype correlations, including the distribution of variants across functional domains.