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.

Although oral antidiabetic agents are widely prescribed for management of type 2 diabetes mellitus (T2DM), their long-term mutagenic and carcinogenic safety remains insufficiently characterized. The aim of this study was to examine the genotoxic potential of empagliflozin, linagliptin, pioglitazone, and the fixed-dose combination (empagliflozin/linagliptin) using Somatic Mutation and Recombination Test (SMART) in . Third-instar larvae from standard (ST) and high-bioactivation (HB) crosses, differing in cytochrome P450 enzyme activity, were chronically exposed to increasing concentrations of selected drugs. Empagliflozin, linagliptin, and their combination did not induce significant alterations in mutant clone frequency across all tested doses in either cross. In contrast, the highest concentration of pioglitazone (72 mg/ml) significantly elevated DNA damage, with lesions originating from both mutation and recombination in the ST cross, but almost exclusively from mutational events in the HB cross. These findings suggest that while empagliflozin and linagliptin present no apparent detectable genotoxic hazard under these tested conditions, pioglitazone displays a dose-dependent genotoxic effect. Data indicate the importance of systematic genotoxicity assessment in widely used antidiabetic medications to ensure patient safety.

Acute kidney injury (AKI) is a complex disease driven by the dynamic coupling of multiple pathological mechanisms. Current treatments remain primarily supportive, making it difficult to achieve precise regulation at key pathological junctures. In recent years, cell-derived nanomaterials (CdNMs) have demonstrated unique advantages in renal-targeted delivery, biocompatibility, and multi-mechanism synergistic regulation, due to their retention of the native biological properties of the source cells. This offers a novel technical pathway to overcome the limitations of traditional nanodelivery systems in AKI treatment. This review systematically summarizes the construction strategies and application progress of CdNMs-including exosomes, cell membrane-coated nanoparticles (CM-NPs), and engineered extracellular vesicles (eEVs)-with a focus on core AKI pathological processes. It further discusses their potential applications in multimodal synergistic therapy and integrated diagnosis-treatment approaches. More importantly, this review proposes a research paradigm in which the design principles of CdNMs are systematically coupled with AKI's pathological dynamics, therapeutic timing, and efficacy evaluation dimensions. This paradigm, driven by a reverse-engineering strategy from pathological mechanisms to material construction and functional assessment, provides methodological references for achieving precise intervention, predictable efficacy evaluation, and optimized clinical translation pathways for AKI.

The composition of polymeric colloidal particle mixtures made from polyacrylates and polyurethanes can be determined at the single nanoparticle level in their solid state using infrared (IR) based Photo-induced Force Microscopy (PiFM). The morphological differences between (1) a blend of two individual polymer dispersions and (2) a hybrid dispersion created by incorporating polyacrylate phases during the preparation of polyurethane particles can be clearly elucidated by detecting the photo-induced force responses originating from materials under irradiation of a tunable IR laser at a wavelength at which one of the polymers shows a strong characteristic IR absorption peak. The hybrid dispersion shows a high degree of mixing between the two chemically distinct species, which would otherwise phase separate in a physical blend. PiFM, with its excellent spatial resolution down to the nanometer scale and spectroscopic similarity to the FT-IR technique, shows strong potential in materials characterization for research areas such as colloids in water-based coatings and micro/nano-plastics.