Biology subjects

Cui, X. T.

Publications and source records attributed to Cui, X. T..

6 recordsLinked to original sources

bioRxiv2026

Zwitterionic polymer coating enabled chronic dopamine sensing and electrophysiology recording in free-moving mice

The brains complex network relies on both electrical and chemical signaling to support its physiological and cognitive functions. To fully understand neural circuit dynamics and their dysfunctions, it is crucial to simultaneously detect neurotransmitters and modulators alongside electrophysiological signals. The striatal dopamine circuits are integral to neurological processes such as movement, reward, learning, and circadian rhythm regulation, making it highly desirable to monitor both neural activity and dopamine (DA) levels in freely behaving animals. One promising approach involves the implantation of multimodal microelectrode arrays (MEAs). However, chronic electrochemical sensing of DA in freely moving animals faces significant challenges, including biofouling of sensing electrodes and the instability of Ag/AgCl reference electrodes. In this study, we developed two complementary strategies--surface grafting and photo crosslinking--to coat the MEA and implanted Ag/AgCl reference electrodes, respectively, with zwitterionic poly(sulfobetaine methacrylate) (PSB). The surface-grafted thin PSB coating effectively inhibits protein fouling and inflammatory responses to the MEA, while the PSB hydrogel protects the Ag/AgCl electrodes from delamination in vivo, ensuring a stable reference potential. By coating both the Ag/AgCl reference electrodes and flexible polyimide MEAs with PSB and PEDOT/CNT, we achieved stable DA detection and electrophysiological recordings in freely moving mice over a four-week period. Weekly electrochemical impedance spectroscopy confirmed the long-term stability of the implanted electrodes. Our method enables multidimensional analysis of behavioral patterns, electrophysiological activity, and DA dynamics, providing a comprehensive approach for neuroscience research. This work advances neurochemical and electrophysiological methodologies by offering reliable tools for longitudinal investigations of brain function in freely behaving animals.

bioengineering↗

bioRxiv2025

Intracortical Microstimulation Induces Rapid Microglia Process Convergence

Intracortical microstimulation (ICMS) has demonstrated the potential to restore vision and hearing by stimulating relevant cortical regions in both animals and humans, offering significant clinical promise for sensory restoration. While the neuronal response to ICMS has been extensively studied at the cellular level through electrophysiology and two-photon (2P) imaging, the response of non-neuronal cells, particularly microglia, as well as the effects of ICMS on blood-brain barrier (BBB) integrity remain poorly understood. In this study, we applied ICMS under 2P imaging in dual-reporter mice, with green fluorescent protein labeling microglia and a red fluorescent Ca2+ indicator labeling neurons. We also monitored vascular dye leakage to assess BBB integrity throughout the experiment. Using clinically relevant waveform parameters, we tested a range of current amplitudes. Surprisingly, we found that microglia responded rapidly, within 15 minutes of stimulation, by converging their processes (MPC) on areas of high neural activity. The prevalence of MPC increased with higher current amplitudes, but intriguingly, it did not correlate with the strength of the local electric field. Additionally, vascular dye penetration into brain tissue was higher in stimulated animals than in controls and increased with current amplitude. This study reveals a rapid microglia and BBB response to ICMS that has not been reported previously, underscoring the need for further research to fully characterize the biological response to ICMS and establish improved safety standards.

bioengineering↗

bioRxiv2024

Potential of Photoelectric Stimulation with Ultrasmall Carbon Electrode on Neural Tissue: New Directions in Neuromodulation Technology Development

ObjectiveNeuromodulation technologies have gained considerable attention for its clinical potential in treating neurological disorders and their capacity to advance cognition research. Nevertheless, traditional neuromodulation methods such as electrical stimulation and optogenetics manipulation currently experience technical and biological challenges that hinge their therapeutic potential and chronic research applications. Recently, a promising alternative neuromodulation approach based on the photoelectric effect has emerged. This approach is capable of generating electrical pulses when exposed to near-infrared (NIR) light and allows modulation of neuronal activity without the need for genetic alterations. In this study, we investigate a variety of design strategies aimed at enhancing photoelectric stimulation using minimally invasive, ultrasmall, untethered carbon electrodes. ApproachA multiphoton laser was employed as the NIR light source. Benchtop investigations were conducted using a three-electrode setup, and chronopotentiometry was used to record photo-stimulated voltage. For in vivo evaluation, we used Thy1-GCaMP6s mice with acute implantation of ultrasmall carbon electrodes. Main resultsWe revealed the beneficial effects of high duty-cycle laser scanning and photovoltaic polymer interfaces on the photo-stimulated voltages of ultrasmall carbon electrodes. Additionally, we demonstrated the promising potential of carbon-based diamond electrodes for photoelectric stimulation and examined the application of photoelectric stimulation in precise chemical delivery by loading mesoporous silica nanoparticles (SNPs) co-deposited with polyethylenedioxythiophene (PEDOT). SignificanceThese findings on photoelectric stimulation utilizing ultrasmall carbon electrodes underscore its immense potential for advancing the next generation of neuromodulation technology. This approach offers the opportunity to effectively modulate neural tissue while minimizing invasive implantation-related injuries in freely moving subjects, which hold significant promise for a wide range of applications in neuroscience research and clinical settings.

bioengineering↗

bioRxiv2023

Real-time in vivo thoracic spinal glutamate sensing reveals spinal hyperactivity during myocardial ischemia

Myocardial ischemia-reperfusion (IR) can cause ventricular arrhythmias and sudden cardiac death via sympathoexcitation. The spinal cord neural network is crucial in triggering these arrhythmias and evaluating its neurotransmitter activity during IR is critical for understanding ventricular excitability control. To assess the real-time in vivo spinal neural activity in a large animal model, we developed a flexible glutamate-sensing multielectrode array. To record the glutamate signaling during IR injury, we inserted the probe into the dorsal horn of the thoracic spinal cord at the T2-T3 where neural signals generated by the cardiac sensory neurons are processed and provide sympathoexcitatory feedback to the heart. Using the glutamate sensing probe, we found that the spinal neural network was excited during IR, especially after 15 mins, and remained elevated during reperfusion. Higher glutamate signaling was correlated with the reduction in the cardiac myocyte activation recovery interval, showing higher sympathoexcitation, as well as dispersion of the repolarization which is a marker for increased risk of arrhythmias. This study illustrates a new technique for measuring the spinal glutamate at different spinal cord levels as a surrogate for the spinal neural network activity during cardiac interventions that engage the cardio-spinal neural pathway. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=76 SRC="FIGDIR/small/531911v2_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@d2e503org.highwire.dtl.DTLVardef@1b93bdeorg.highwire.dtl.DTLVardef@99ceaorg.highwire.dtl.DTLVardef@11d053e_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Implantable flexible multielectrode arrays for multi-site sensing of serotonin tonic levels

Real-time multi-channel measurements of tonic serotonin (5-hydroxytryptamine, 5-HT) concentrations across different brain regions are of utmost importance to the understanding of 5-HTs role in anxiety, depression, and impulse control disorders, which will improve the diagnosis and treatment of these neuropsychiatric illnesses. Chronic sampling of 5-HT is critical in tracking disease development as well as the time course of pharmacological treatments. Despite their value, in vivo chronic multi-site measurements of 5-HT have not been reported. To fill this technological gap, we batch fabricated implantable glassy carbon (GC) microelectrode arrays (MEAs) on a flexible SU-8 substrate to provide an electrochemically stable and biocompatible device/tissue interface. Then, to achieve multi-site detection of tonic 5-HT concentrations, we incorporated the poly(3,4-ethylenedioxythiophene)/functionalized carbon nanotube (PEDOT/CNT) coating on the GC microelectrodes in combination with a new square wave voltammetry (SWV) approach, optimized for selective 5-HT measurement. In vitro, the PEDOT/CNT coated GC microelectrodes achieved high sensitivity towards 5-HT, good fouling resistance in the presence of 5-HT, and excellent selectivity towards the most common neurochemical interferents. In vivo, our PEDOT/CNT-coated GC MEAs were able to successfully detect basal 5-HT concentrations at different locations of the CA2 hippocampal region of mice in both anesthetized and awake head-fixed conditions. Furthermore, the implanted PEDOT/CNT-coated MEA achieved stable detection of tonic 5-HT concentrations for one week. Finally, histology data in the hippocampus shows reduced tissue damage and inflammatory responses compared to stiff silicon probes. To the best of our knowledge, this PEDOT/CNT-coated GC MEA is the first implantable flexible multisite sensor capable of chronic in vivo multi-site sensing of tonic 5-HT. This implantable MEA can be custom-designed according to specific brain region of interests and research questions, with the potential to combine electrophysiology recording and multiple analyte sensing to maximize our understanding of neurochemistry. HighlightsO_LIPEDOT/CNT-coated GC microelectrodes enabled sensitive and selective tonic detection of serotonin (5-HT) using a new square wave voltammetry (SWV) approach C_LIO_LIPEDOT/CNT-coated GC MEAs achieved multi-site in vivo 5-HT tonic detection for one week. C_LIO_LIFlexible MEAs lead to reduced tissue damage and inflammation compared to stiff silicon probes. C_LI

bioengineering↗

bioRxiv2022

Integrated microprism and micro-electrode array for chronic in vivo two-photon imaging and electrophysiology across all cortical layers

Electrophysiology is a vital tool in neuroscience research with increasing translational value. It is used to record or modulate neuronal activity with high temporal but lower spatial resolution. Optical technologies, such as two-photon microscopy (TPM) can complement electrophysiological recordings with large-scale imaging at cellular resolution. Combining these two provides a powerful platform to elucidate and coordinate multimodal functions. Prior attempts have been limited to the superficial brain from a top-down optical view. Here, we describe a novel combination of transparent microelectrode arrays (MEAs) with glass microprisms for simultaneous electrophysiology and optical imaging of all cortical layers in a vertical plane. We tested our device in Thy1-GCaMP6 mice for over 4 months and demonstrated its capability for multisite single-unit recording, microstimulation, and simultaneous TPM calcium imaging. Using this setup, we reveal how amplitude, frequency, and depth of microstimulation impact neural activation patterns across the cortical column. This work presents a multimodal tool that extends integrated electrophysiology and optical imaging from the superficial brain to the whole cortical column, opening new avenues of neuroscience research and neurotechnology development.

bioengineering↗