Cholinergic control of striatal GABAergic microcircuits.
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.
Three-dimensional voltage imaging in live larval zebrafish brains using fully genetically encoded voltage indicator.
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.
Red-shifted GRAB acetylcholine sensors for multiplex imaging in vivo.
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.
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Basal Ganglia Advances
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.
Progress in Voltage Imaging
Recent advances in the field of Voltage Imaging, with a special focus on new constructs and novel implementations.
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Work related to place tuning, spatial navigation, orientation and direction. Mainly includes articles on connectivity in the hippocampus, retrosplenial cortex, and related areas.
Most Popular Recent Articles
The antioxidant and α-glucosidase inhibitory compounds isolated from the roots of Fisch.
As a 'medicine food homology' herbal medicine, Fisch. has been consumed widely in the pharmaceutical and food industries. In this paper, seventeen known compounds () were isolated from the ethyl acetate fraction of roots. Their structures were elucidated as isoliquiritin , liquiritigenin , liquiritin , ononin , quercetin , 2,4-dihydroxybenzoic acid , isoliquiritigenin , kaempferol , rutin , naringenin , isolicoflavonol , licoflavonol , β-sitosterol , p-hydroxyphenethylanisate , 6,8-diprenylgenistein luteolin and p-hydroxybenzoic acid . Among them, compounds and were verified with significant α-glucosidase inhibitory activity with IC of 1.9 and 2.6 M for the first time, respectively. Compounds , , and exhibited distinctive antioxidant efficacies. Additionally, the structure-activity relationship analysis has been discussed. Herein, this paper highlights that the ethyl acetate fraction of is a potentially natural source for exploring antioxidant and antidiabetic constituents.
Modular PEG coatings for engineering a biomimetic glycocalyx on lipid membranes.
Engineering synthetic cells with biomimetic surface architectures requires precise control over the spatial organization and mechanical properties of the membrane surface. Inspired by the protective and regulatory functions of the natural glycocalyx, we present a modular platform for constructing hierarchical, crosslinked PEG networks on fluid lipid membranes. Through spatially controlled, sequential strain-promoted azide-alkyne cycloaddition (SPAAC), we assemble a tunable, multilayered PEG mesh that mimics the dynamic, dense, and mechanically resilient architecture of the glycocalyx. By incorporating linear PEG lipids as defined anchors at controlled densities (0.25-1 mol%), we establish a reactive scaffold on the membrane surface. Sequential conjugation with eight-arm PEG-DBCO and eight-arm PEG-azide enables the formation of a covalently crosslinked, multilayered PEG mesh with tunable thickness, connectivity, and mechanical robustness. The multivalency of the eight-arm architecture allows each first-layer PEG to act as a branching node, enabling high-density network formation and exceeding the surface coverage achievable with linear PEG chains. Crucially, the phase-dependent partitioning of the lipid anchor enables a spatially confined network assembly within the liquid-disordered (L) domains of phase-separated membranes, allowing for domain-specific functionalization. Once formed, the crosslinked network exhibits persistent spatial organization, retaining its footprint even after thermal mixing of the underlying lipid phase-a hallmark of mechanical stability and functional memory. Quantitative analysis QCM-D and FRAP reveals that network connectivity and lateral mobility are governed by anchor density and PEG architecture. The resulting mesh acts as a tunable steric barrier, effectively attenuating receptor-ligand interactions in a stepwise, assembly-dependent manner. This work demonstrates a powerful strategy for engineering programmable, adaptive, and mechanically resilient surface architectures on model membranes, a critical step toward interfacing functional synthetic cells with intelligent nanocarriers of spatiotemporally regulated functionality.
Diagnostic Performance of CT/MRI-Based Lymph Node Morphology With Three-Plane Size Measurements in Oral Cavity Cancer.
This study evaluates the diagnostic value of CT/MRI-based nodal morphology and three-plane size criteria for identifying pathologically positive (pN+) cervical lymph nodes (LNs) in oral squamous cell carcinoma (OSCC).