Cholinergic interneurons (CINs) are essential elements of striatal circuits and functions. Although acetylcholine signaling via muscarinic receptors (mAChRs) has been well studied, more recent data indicate that postsynaptic nicotinic receptors (nAChRs) located on striatal GABAergic interneurons (GINs) are equally critical. One example is that CIN stimulation induces large disynaptic inhibition of striatal projection neurons (SPNs) mediated by nAChR activation of GINs. Although these circuits are ideally positioned to modulate striatal output, the neurons involved are not definitively identified because of an incomplete mapping of CINs-GINs interconnections. Here, we show that CINs modulate four GINs populations via an intricate mechanism involving co-activation of presynaptic and postsynaptic mAChRs and nAChRs. Using optogenetics, we demonstrate the participation of tyrosine hydroxylase-expressing GINs in the disynaptic inhibition of SPNs via heterotypic electrical coupling with neurogliaform interneurons. Altogether, our results highlight the importance of CINs in regulating GINs microcircuits via complex synaptic/heterosynaptic mechanisms.

Voltage imaging has emerged as a powerful tool for recording membrane potential changes in living cells, offering a direct measurement of rapid neuronal events with high temporal precision. Since the brain is a three-dimensional circuit, it is essential to record signals across a volume. However, achieving effective three-dimensional voltage imaging over large neuronal populations remains challenging due to the need for high imaging speed, high signal-to-noise ratio, and extensive volume coverage. In this study, we demonstrate in vivo three-dimensional voltage imaging in larval zebrafish using oblique plane microscopy and QFDBD-QUAS-driven expression of the genetically encoded voltage indicator Ace-mNeon2-Kv2.1, achieving volumetric imaging rates of up to 200 volumes per second (VPS). This approach enables dye-free voltage imaging, simplifying experimental workflows and improving the reproducibility of in vivo voltage imaging experiments for investigating neuronal circuit dynamics in the living zebrafish animal model.

The neurotransmitter acetylcholine (ACh) is essential in both the central and peripheral nervous systems. Recent studies highlight the significance of interactions between ACh and various neuromodulators in regulating complex behaviors. The ability to simultaneously image ACh and other neuromodulators can provide valuable information regarding the mechanisms underlying these behaviors. Here we developed a series of red fluorescent G-protein-coupled receptor activation-based ACh sensors, with a wide detection range and expanded spectral profile. The high-affinity sensor rACh1h reliably detects ACh release in various brain regions, including the nucleus accumbens, amygdala, hippocampus and cortex. Moreover, rACh1h can be coexpressed with green fluorescent sensors to record ACh release together with other neurochemicals in various behavioral contexts using fiber photometry, mesoscopic imaging and two-photon imaging with high spatiotemporal resolution.

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.

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.

Tetrasodium pyrophosphate (TSPP) is a widely used phosphate-based food additive that may contribute to exogenous inorganic phosphate exposure, however, its potential role in renal fibrosis remains poorly understood. This study investigated the molecular targets and mechanisms underlying TSPP-induced renal fibrosis using integrative network toxicology combined with experimental validation. Network toxicology identified 39 overlapping targets, which were mainly enriched in renal tubular ion transport, ion homeostasis, and mineral metabolism. Target prioritization and transcriptomic analysis further identified SLC5A2, a proximal tubular sodium-glucose cotransporter involved in tubular reabsorptive function, as a key candidate target. In HK-2 cells, exogenous TSPP at 5 μM suppressed SLC5A2 expression and induced inflammatory and profibrotic responses. Conversely, these effects were partially attenuated by SLC5A2 overexpression. These findings suggest that TSPP may contribute to renal fibrosis by downregulating SLC5A2 and disrupting proximal tubular transport homeostasis, thereby promoting inflammatory and profibrotic responses. Our results provide mechanistic insights into phosphate additive-associated renal fibrosis and highlight the chronic renal health risks associated with dietary and environmental exposure to TSPP, particularly in populations with impaired renal function.

Localized surface plasmon resonance (LSPR) biosensors offer high sensitivity, potential for miniaturization, and compatibility with microfluidic platforms. But their broader application is limited by the instability and cost of conventional thiol-based biofunctionalization strategies. In this work, we report a robust microfluidic-based biofunctionalization approach that uses an ultrathin silica coating of Au NPs, followed by epoxy-silane modification. An LSPR microfluidic sol-gel process was used to deposit an ultrathin silica shell (4.5 nm) on immobilized 80 nm Au NPs, enabling thickness control while preserving plasmonic performance. The impact of the silica layer on both the bulk and surface refractive-index sensitivities was systematically evaluated using ethylene glycol solutions and layer-by-layer polyelectrolyte deposition, respectively. The ultrathin coating resulted in only a minor reduction in bulk sensitivity (1.88 nm RIU) while retaining 75-77% of the surface refractive-index sensitivity. Subsequent epoxy-silane functionalization enabled stable covalent attachment of amino-terminated DNA probes, as verified by LSPR and Raman spectroscopy. A proof-of-concept DNA hybridization assay demonstrated specific binding of complementary targets under microfluidic conditions. The presented approach overcomes key limitations of thiol chemistry and provides a stable, versatile, and microfluidics-compatible platform for LSPR bioanalytics.