Dopamine is essential for striatal function and learning. Striatal dopamine release can be triggered by dopamine cell firing, but also by coordinated cholinergic interneuron activity, which stimulates dopamine release via presynaptic nicotinic acetylcholine receptors on dopamine axons. While acetylcholine-dependent dopamine release is well-documented ex vivo and under artificial optogenetic stimulation in vivo, its role during natural behavior has remained unclear. One possible endogenous driver of acetylcholine-dependent dopamine release is thalamic input, which provides strong excitatory drive to cholinergic interneurons. To examine whether thalamic input provokes acetylcholine-dependent dopamine release during behavior, we performed simultaneous fiber photometry recordings of striatal dopamine (GRAB-rDA3m) and thalamic axon activity (gCaMP8m) in the dorsomedial (DMS) and dorsolateral striatum (DLS) of mice learning the accelerating rotarod, a striatal-dependent task that demands precise and effortful motor control. Recordings were obtained on- and off-task and across days of training to capture the full arc of learning. Dopamine transients in DMS, but not DLS, were frequently coupled to peaks in thalamic axon activity via an acetylcholine-dependent mechanism. The occurrence of these thalamic-evoked DMS dopamine transients depended on learning, task engagement, and the recent history of dopamine activity, but did not contribute to motor error signals. Together, these findings establish thalamic input as a physiological driver of acetylcholine-dependent dopamine release in DMS. Moreover, they reveal that striatal sensitivity to this local release mechanism is dynamically gated by dopaminergic history, providing a compelling framework for understanding how local and soma-triggered dopamine signals are coordinated to support learning.

High-resolution extracellular electrophysiology is the gold standard for recording spikes from distributed neural populations and is especially powerful when combined with optogenetics for manipulation of specific cell types with high temporal resolution. We integrated these approaches into prototype Neuropixels Opto probes, which combine electronic and photonic circuits. These devices pack 960 electrical recording sites and two sets of 14 light emitters onto a 70-μm-wide, 1-cm-long shank, allowing spatially addressable optogenetic stimulation with blue and red light. In mouse cortex, Neuropixels Opto probes delivered high-quality recordings together with spatially addressable optogenetics, differentially activating or silencing neurons at distinct cortical depths. In the mouse striatum and other deep structures, Neuropixels Opto probes delivered efficient optotagging, facilitating the identification of two cell types in parallel. Neuropixels Opto probes represent a promising tool for recording, identifying and manipulating neuronal populations.

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.

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.

Despite major advances in reperfusion therapy and pharmacological management, acute myocardial infarction (AMI) remains one of the leading causes of mortality and morbidity worldwide. Conventional treatment strategies primarily focus on restoring coronary blood flow to ischemic myocardium; however, their ability to regenerate damaged cardiac tissue remains limited. In recent years, exosomes have emerged as a promising cell-free therapeutic approach for cardiac repair following AMI. Exosomes are nanosized extracellular vesicles secreted by various cell types that carry diverse bioactive molecules, including microRNAs, proteins, lipids, and signaling factors, which mediate intercellular communication and regulate multiple biological processes involved in myocardial healing. Emerging experimental and preclinical evidence suggests that exosome-based therapy may attenuate inflammation, reduce cardiomyocyte apoptosis, enhance angiogenesis, modulate immune responses, and promote myocardial regeneration following ischemic injury. Compared with conventional stem cell therapy, exosomes offer several advantages, including lower immunogenicity, reduced risk of tumorigenicity, improved stability, and easier storage and handling. Furthermore, engineered exosomes and targeted delivery systems are being investigated to enhance therapeutic specificity and efficacy in cardiovascular diseases. In addition to their therapeutic potential, circulating exosomes are also being explored as diagnostic and prognostic biomarkers for the early detection and monitoring of AMI. This review highlights the biological characteristics of exosomes, their mechanisms of action in myocardial repair, current experimental and clinical evidence, and future perspectives of exosome-based therapeutics in the management of AMI.

Current guidelines recommend endoscopic variceal ligation (EVL) and endoscopic cyanoacrylate injection (ECI) for esophageal and fundal variceal bleeding, respectively. However, the optimal strategy for treating acute variceal bleeding (AVB) from the cardia to the lesser curvature remains undefined. This study compared the efficacy of EVL and ECI for AVB at this region.

In 2016 the American Board of Surgery introduced Entrustable Professional Activities (EPAs) as an assessment framework to support competency-based education within General Surgery. EPAs operationalize milestones and competencies into a practical assessment framework, enabling timely, targeted feedback and progressive entrustment.