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.
Navigation & Localization
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
Algorithm-Based Decision-Making on the Need for Antimicrobial Treatment in Hospitalized Children With Respiratory Tract Infections: A Retrospective Study.
National Burden of Human Adenovirus Infections in China: A Community-Based Multiplier Modeling Study.
Human adenovirus (HAdV) is an important cause of respiratory infections, yet community-level burden estimates remain limited. We aimed to estimate post-pandemic HAdV burden in China. Using nationwide respiratory pathogen surveillance data and a multiplier model, we estimated the incidence of HAdV infections, symptomatic illnesses (SI), and medically attended illnesses (MAI) in China from 2023 to 2024. Age-, species-, and province-specific analyses were conducted. Uncertainty was assessed using Monte Carlo simulations. We estimated 44.21 million HAdV infections (95% UI, 26.68-77.08 million) over the 19-month study period, corresponding to an average monthly incidence of 1.58 per 1000 persons (95% UI, 1.01-2.61), equivalent to an annualized incidence of 18.96 per 1000 persons (95% UI, 12.12-31.32). The estimated average monthly incidences of SI and MAI were 0.41 (95% UI, 0.30-0.57) and 0.30 (95% UI, 0.21-0.40) per 1000 persons, corresponding to annualized incidences of 4.92 (95% UI, 3.60-6.84) and 3.60 (95% UI, 2.52-4.80) per 1000 persons, respectively. Children aged 0-4 years had the highest average monthly incidence (16.66 [95% UI, 10.26-28.54] per 1000 persons). HAdV species B showed higher incidence than species C among children aged 5-14 years. The highest incidence rates occurred in several south-central and southwestern provinces, including Hunan, Guangxi, Hubei, Guangdong, and Yunnan. HAdV imposed a substantial and under-recognized respiratory disease burden in China during the post-pandemic period. Children experienced the highest burden, and marked species-specific and geographic heterogeneity were observed. These findings provide community-based evidence to inform adenovirus surveillance and respiratory disease control strategies in China.
Curving Actin Across Systems: Do Axonal Actin Rings Share Common Underlying Mechanisms?
Actin polymerization into curved and ring-shaped structures is an evolutionarily conserved mechanism that cells use to generate force, transmit tension, and maintain membrane architecture. In neurons, super-resolution imaging has revealed a striking periodic submembranous scaffold in axons, composed of circumferential actin rings interconnected by spectrin tetramers, known as the membrane periodic skeleton (MPS). This structure is widely conserved across species and neuronal subtypes and contributes to axonal integrity by reinforcing mechanical stability, organizing membrane proteins, regulating endocytosis, modulating axon caliber, and providing a transient platform for signaling. Although significant progress has been made in defining MPS functions, the molecular mechanisms governing the nucleation, assembly, and maintenance of axonal actin rings remain poorly understood. Here, we explore actin ring formation through comparison with three mechanistically informative systems: cytokinetic contractile rings, epithelial wound-edge purse strings, and adherens junction-associated actin belts. Across these contexts, ring assembly can be parsed into a series of conserved stages, including spatial confinement, membrane anchoring, actin nucleation and elongation, multivalent scaffolding, filament cross-linking and stabilization, regulated turnover, and force production. This comparative perspective uncovers shared design principles that may also apply to axons and offers a conceptual framework for dissecting the molecular basis of MPS nucleation, assembly, and long-term stability.