Biology subjects

Bi, G.-Q.

Publications and source records attributed to Bi, G.-Q..

8 recordsLinked to original sources

bioRxiv2026

Precision cooling assists electrical stimulation: Breaking selectivity barriers in nerve control

Peripheral neuromodulation can relieve pain through sensory activation or conduction block. However, electrical stimulation of mixed nerves couples these intended effects to unwanted neural activity. Here we demonstrate local cooling can separate targeted from off-target neural activity. In the rat sciatic nerve, precooling reduced the onset response to kilohertz-frequency stimulation by about 90% and maintained block in the target pathway during rewarming. During low-frequency stimulation, spatially graded cooling suppressed A{delta} enriched activity and blocked nontarget propagation. This produced a directional, A{beta} biased afferent output. A cooling-electrical neural digital twin predicted both responses and linked them to field-edge transition dynamics and spatially separated control of recruitment and conduction. These findings provide a mechanistically grounded route beyond the targeting limits of electrical stimulation alone.

bioengineering↗

bioRxiv2025

High-speed mapping of whole-mouse peripheral nerves at subcellular resolution

In contrast to the rapid advancements in mesoscale connectomic mapping of the mammalian brain, similar mapping the peripheral nervous system has remained challenging due to the bodys size and complexity. Here, we present a high-speed blockface volumetric imaging system with an optimized workflow of whole-body clearing, capable of imaging the entire adult mouse at micrometer resolution within 40 hours. Three-dimensional reconstruction of individual spinal fibers in Thy1-EGFP mice reveals distinct morphological features of sensory and motor projections along the ventral and dorsal rami. Immunostaining facilitates body-wide mapping of sympathetic nerves and their branches, highlighting their perivascular patterns in limb muscles, bones, and most visceral organs. Viral tracing elucidates the fine architecture of vagus nerves and individual vagal fibers, revealing unexpected projection routes to various organs. Our approach offers an effective means to achieve a holistic understanding of cellular-level interactions among different systems that underlie body physiology and disease. HighlightsO_LIImaging of whole adult mouse at uniform subcellular resolution within 40 hours C_LIO_LIReconstruction of 191 thoracic spinal neuron projections for Thy1-EGFP mice C_LIO_LIMapping of immunolabeled sympathetic projections and their perivascular patterns C_LIO_LIResolving virus-labeled architecture of vagus nerves and complex single-fiber routes C_LI

neuroscience↗

bioRxiv2023

Multi-region calcium imaging in freely behaving mice with ultra-compact head-mounted fluorescence microscopes

To investigate the circuit-level neural mechanisms of behavior, simultaneous imaging of neuronal activity in multiple cortical and subcortical regions is highly desired. Miniature head-mounted microscopes offer the capability of calcium imaging in freely behaving animals. However, implanting multiple microscopes on a mouse brain remains challenging due to space constraints and the cumbersome weight of equipment. Here, we present TINIscope, a Tightly Integrated Neuronal Imaging microscope optimized for electronic and opto-mechanical design. With its compact and lightweight design of 0.43 g, TINIscope enables unprecedented simultaneous imaging of behavior-relevant activity in up to four brain regions in mice. Proof-of-concept experiments with TINIscope recorded over 1000 neurons in four hippocampal subregions and revealed concurrent activity patterns spanning across these regions. Moreover, we explored potential multi-modal experimental designs by integrating additional modules for optogenetics, electrical stimulation or local field potential recordings. Overall, TINIscope represents a timely and indispensable tool for studying the brain-wide interregional coordination that underlies unrestrained behaviors.

neuroscience↗

bioRxiv2021

Multi-Functionalized Self-Bonding MXene for Minimal-invasive Jet-injected Neural Interface and Tissue Healing

Implantable central and peripheral neural interfaces have great potential in treating various nerve injuries and diseases. Still, limitations of surgery trauma, handling inconvenience, and biocompatibility issues of available materials and techniques significantly hinder the peripheral nerve interface for research and clinical purposes. MXenes have great potential as bioelectronics materials for excellent hydrophilicity, conductivity, and biocompatibility. However, their application in bioelectronic interface has been limited due to the poor oxidation stability and fast tissue clearance. Here, we developed a minimal-invasive jet-injected neural interface using MXene nanosheets with strong redox stability, tissue adhesion, conductivity, and good self-bonding properties. We also develop a minimal-invasive jet injector to implant the optimized MXene suspension into the damaged sciatic nerve and establish a neural interface through tissue adhesion and self-bonding. We use this neural interface to promote nerve regeneration and perform electrophysiology recording on moving mice. We prove that the nanosheets can mitigate cellular inflammation, promote tissue healing, and record high-quality electrophysiology signals for predicting joint movement. Thus, our material and implantation strategy together form a novel minimal-invasive neural interface, facilitating the collection and analysis of large-scale living body data to solve the challenge of neurological diseases of the peripheral or even the central nervous system.

bioengineering↗

bioRxiv2021

Isotropic Reconstruction of Electron Tomograms with Deep Learning

Cryogenic electron tomography (cryoET) allows visualization of cellular structures in situ. However, anisotropic resolution arising from the intrinsic "missing-wedge" problem has presented major challenges in visualization and interpretation of tomograms. Here, we have developed IsoNet, a deep learning-based software package that iteratively reconstructs the missing-wedge information and increases signal-to-noise ratio, using the knowledge learned from raw tomograms. Without the need for sub-tomogram averaging, Isonet generates tomograms with significantly reduced resolution anisotropy. Applications of IsoNet to three representative types of cryoET data demonstrate greatly improved structural interpretability: resolving lattice defects in immature HIV particles, establishing architecture of the paraflagellar rod in Eukaryotic flagella, and identifying heptagon-containing clathrin cages inside a neuronal synapse of cultured cells. Therefore, by overcoming two fundamental limitations of cryoET, IsoNet enables functional interpretation of cellular tomograms without sub-tomogram averaging. Its application to high-resolution cellular tomograms should also help identify differently oriented complexes of the same kind for near-atomic resolution sub-tomogram averaging.

cell biology↗

bioRxiv2020

High-throughput whole-brain mapping of rhesus monkey at micron resolution

Whole-brain mesoscale mapping of primates has been hindered by large brain size and the relatively low throughput of available microscopy methods. Here, we present an integrative approach that combines primate-optimized tissue sectioning and clearing with ultrahigh-speed, large-scale, volumetric fluorescence microscopy, capable of completing whole-brain imaging of a rhesus monkey at 1 {micro}m x 1 {micro}m x 2.5 {micro}m voxel resolution within 100 hours. A progressive strategy is developed for high-efficiency, long-range tracing of individual axonal fibers through the dataset of hundreds of terabytes, establishing a "Serial sectioning and clearing, 3-dimensional Microscopy, with semi-Automated Reconstruction and Tracing" (SMART) pipeline. This system supports effective connectome-scale mapping of large primates that reveals distinct features of thalamocortical projections of the rhesus monkey brain at the level of individual axonal fibers.

neuroscience↗

bioRxiv2020

Mesophasic organization of GABAA receptors in hippocampal inhibitory synapse

Information processing in the brain depends on synaptic transmission and plasticity, which in turn require specialized organization of neurotransmitter receptors and scaffolding proteins within the postsynaptic density (PSD). However, how these molecules are organized in situ remains largely elusive, limiting our mechanistic understanding of synaptic formation and functions. Here, we have developed template-free classification of over-sampled sub-tomograms to analyze cryo-electron tomograms of hippocampal synapses, enabling us to identify type-A {gamma}-aminobutyric acid receptor (GABAAR) in inhibitory synapses and determine its in situ structure at 19 [A] resolution. We found that these receptors are organized hierarchically: from GABAAR super-complexes with a fixed 11-nm inter-receptor distance but variable relative angles, through semi-ordered two-dimensional receptor networks with reduced Voronoi entropy, to mesophasic assembly with a sharp phase boundary. This assembly aligns with condensates of postsynaptic scaffolding proteins and putative presynaptic vesicle release sites. Such mesophasic self-organization may allow synapses to achieve a "Goldilocks" state with a delicate balance between stability and flexibility, enabling both reliability and plasticity in information processing.

neuroscience↗

bioRxiv2017

Scalable volumetric imaging for ultrahigh-speed brain mapping at synaptic resolution

We describe a new light-sheet microscopy method for fast, large-scale volumetric imaging. Combining synchronized scanning illumination and oblique imaging over cleared, thick tissue sections in smooth motion, our approach achieves high-speed 3D image acquisition of an entire mouse brain within 2 hours, at a resolution capable of resolving synaptic spines. It is compatible with immunofluorescence labeling, enabling flexible cell-type specific brain mapping, and is readily scalable for large biological samples such as primate brain.

neuroscience↗