Biology subjects

Li, B.-Z.

Publications and source records attributed to Li, B.-Z..

11 recordsLinked to original sources

bioRxiv2026

High precision animal stereotaxis with 3D polychromic photogrammetry

Stereotaxic brain surgery is a foundational neurosurgical technique used to deliver chemical, pharmacological, or genetic material to specific brain regions, or to precisely implant electrodes and stimulators. Accurate targeting depends on reliable identification of skull landmarks, particularly bregma and lambda. Here we present a photogrammetry-based automated small animal stereotaxic platform that uses a single, freely handheld camera, such as a standard smartphone, to generate high-resolution, polychromatic 3D skull reconstructions. Because photogrammetry requires no fixed overhead hardware, the surgical field remains fully accessible for instruments, microscopes, and other equipment. The resulting color reconstructions substantially improve identification of bregma and lambda compared to monochromatic approaches, and the higher spatial resolution translates directly into improved targeting accuracy and surgical speed. The system operates by a user moving a handheld camera around the exposed skull. The platform automatically produces a detailed 3D mesh and computes stereotaxic coordinates without manual measurement. Together, these properties yield a practical, accessible yet accurate platform for automated small animal neurosurgery. We previously described a structured illumination approach in combination with a Steward platform; however, that system required a fixed projector and camera array that occupied critical surgical workspace and produced monochromatic meshes that complicated landmark identification. The photogrammetry-based method described here overcomes both limitations while retaining full compatibility with the Steward platform as a stereotaxic base.

neuroscience↗

bioRxiv2026

Smad7-based biologic targeting epidermis and stroma promotes healing of diabetic wounds in mice and pigs

This study aimed to identify novel mechanisms of diabetic wound healing defects and test a therapeutic intervention using diabetic mouse and pig models. We found Smad7 transgene expression in mouse epidermis promoted wound healing in diabetic mice. To isolate effects of Smad7 on wounds, we created a Smad7-based biologic (Tat-PYC-Smad7) that penetrated cells of the wound. Topical Tat-PYC-Smad7 treatment to diabetic pig and mouse wounds accelerated healing compared to vehicle controls. Tat-PYC-Smad7-treated wounds showed reduced TGF{beta}/NF{kappa}B signaling, faster re-epithelialization and better extracellular matrix remodeling. Tat-PYC-Smad7 also attenuated neutrophil NETosis, potentially acting through reductions in MPO enzymatic activity and MPO nuclear entry, consequently reducing chromatin decondensation and the release of NET components. Our study revealed that Tat-PYC-Smad7 promoted diabetic wound healing by targeting keratinocytes and neutrophils, providing insight into mechanisms of diabetic wound healing defects targetable by Smad7-based therapy.

immunology↗

bioRxiv2025

In-vivo optogenetic manipulation approach for gerbil medial nucleus of trapezoid body

PurposeThis study introduces an in-vivo optogenetic manipulation approach for the medial nucleus of the trapezoid body (MNTB) in Mongolian gerbils, a species with a hearing range similar to humans. The MNTB is crucial for sound localization, but traditional methods lack temporal precision and reversibility. The aim of this study is to develop a specific, reversible method for controlling MNTB activity with fast and precise temporal control, an approach vital for studying sound localization. MethodsWe stereotactically injected adeno-associated viral vectors encoding opsins into the gerbil MNTB. Precise targeting was achieved despite the MNTBs location in a deep, heavily myelinated area of the brainstem. Opsin expression was confirmed via confocal microscopy. In-vivo electrophysiology combined with optical stimulation was used to test optical activation and suppression of MNTB activity during sound stimuli. ResultsOpsin expression was strong and stable in MNTB neurons over weeks and months. Laser stimulation during in-vivo recordings successfully induced both activation and suppression of MNTB neurons, demonstrating fast and precise control over neural activity. ConclusionThis in-vivo optogenetic method provides specific, reversible control of MNTB activity in gerbils with rapid, real-time modulation. It offers a powerful tool for investigating sound localization and auditory processing with high temporal precision.

neuroscience↗

bioRxiv2024

VARIATION IN HEAD AND PINNA MORPHOLOGY OF PRESERVED PEROMYSCUS SPP. SPECIMENS AND IMPLICATIONS FOR AUDITORY FUNCTION

The characteristics of an animals head and pinna mark the beginning of auditory communication. Auditory communication is broadly achieved by receiving sounds from the environment and plays a vital role in an animals ability to perceive and localize sounds. Natural history museums and collections along with their vast repositories of specimens provide a unique resource for examining how the variability in both the size and shape of the head and pinna cause variability in the detection of acoustic signals across species. Using this approach, we measured the dimensions of the head and pinna of over 1,200 preserved specimens of Peromyscus boylii, P. californicus, P. gossypinus, P. leucopus, P. maniculatus, and P. truei, followed by a series of head-related transfer functions (HRTFs) on several individuals to study the relationship between morphology and available auditory information. Our morphological results show significant variation in pinna length and width, as well as in the distance between the two ears across the six species. ITDs and ILDs were calculated and demonstrated consistent results across species, suggesting the differences in head and pinna size do not significantly modify these cues. Not only does this study contribute to existing research on external morphology and auditory function, but it also provides valuable insight into the use of preserved specimens in auditory research, an area that is currently understudied. Summary statementThis work aims to provide insight into using natural history museum specimens for morphological research pertaining to the auditory system in small mammals.

evolutionary biology↗

bioRxiv2024

Hearing in Two Closely Related Peromyscus Species (Peromyscus maniculatus and P. leucopus)

The genus Peromyscus has been extensively used as a model for ecological, behavioral, and evolutionary studies. We used auditory brainstem responses (ABRs), craniofacial morphology, and pinna measurements to compare characteristics that could impact the threshold, amplitude, and latency of ABRs in two wild-caught species, P. leucopus and P. maniculatus. We observed significant differences in craniofacial and pinna attributes between species, with P. leucopus exhibiting larger features and bigger overall size compared to P. maniculatus. ABR recordings showed similar hearing thresholds with peak sensitivity between 8 to 46 kHz for both species. We found that amplitude of ABR wave I and IV increased significantly with increasing intensity, while no main effect of species was detected. Latency of wave I and IV significantly decreased with increasing intensity in both species. Finally, we observed longer latencies of the binaural interaction component (BIC) at longer interaural time differences (ITDs) in P. leucopus, while no differences were observed across relative BIC amplitude between species. These results provide additional ABR related data that expands the use of both Peromyscus species as future models for auditory research.

neuroscience↗

bioRxiv2024

Sapphire-Based Optrode for Low Noise Neural Recording and Optogenetic Manipulation

Electrophysiological recordings of neurons in deep brain regions using optogenetic stimulation are essential to understanding and regulating the role of complex neural activity in biological behavior and cognitive function. Optogenetic techniques have significantly advanced neuroscience research by enabling the optical manipulation of neural activities. Because of the significance of the technique, constant advancements in implantable optrodes that integrate optical stimulation with low-noise, large-scale electrophysiological recording are in demand to improve the spatiotemporal resolution for various experimental designs and future clinical applications. However, robust and easy-to-use neural optrodes that integrate neural recording arrays with high-intensity light emitting diodes (LEDs) are still lacking. Here, we propose a neural optrode based on Gallium Nitride (GaN) on sapphire technology, which integrates a high-intensity blue LED with a 5x2 recording array monolithically for simultaneous neural recording and optogenetic manipulation. To reduce the noise interference between the recording electrodes and the LED, which is in close physical proximity, three metal grounding interlayers were incorporated within the optrode, and their ability to reduce LED-induced artifacts during neural recording was confirmed through both electromagnetic simulations and experimental demonstrations. The capability of the sapphire optrode to record action potentials has been demonstrated by recording the firing of mitral/tuft cells in the olfactory bulbs of mice in vivo. Additionally, the elevation of action potential firing due to optogenetic stimulation observed using the sapphire probe in medial superior olive (MSO) neurons of the gerbil auditory brainstem confirms the capability of this sapphire optrode to precisely access neural activities in deep brain regions under complex experimental designs.

neuroscience↗

bioRxiv2024

Computational model for synthesizing auditory brainstem responses to assess neuronal alterations in aging and autistic animal models

PurposeThe auditory brainstem response (ABR) is a widely used objective electrophysiology measure for non-invasively assessing auditory function and neural activity in the auditory brainstem, but its ability to reflect detailed neuronal processing is limited due to the averaging nature of the electroencephalogram-type recordings. MethodThis study addresses this limitation by developing a computational model of the auditory brainstem which is capable of synthesizing ABR traces based on a large, population scale neural extrapolation of a spiking neuronal network of auditory brainstem circuitry. The model was able to recapitulate alterations in ABR waveform morphology that have been shown to be present in two medical conditions: animal models of autism and aging. Moreover, in both of these conditions, these ABR alterations are caused by known distinct changes in auditory brainstem physiology, and the model could recapitulate these changes. ResultsIn the autism model, the simulation revealed myelin deficits and hyperexcitability, which caused a decreased wave III amplitude and a prolonged wave III-V interval, consistent with experimentally recorded ABRs in Fmr1-KO mice. For the aging condition, the model recapitulated ABRs recorded in aged gerbils and indicated a reduction in activity in the medial nucleus of the trapezoid body (MNTB), a finding validated by confocal imaging data. ConclusionThese results demonstrate not only the models accuracy but also its capability of linking features of ABR morphology to underlying neuronal properties and suggesting follow-up physiological experiments.

neuroscience↗

bioRxiv2024

Age-related myelin deficits in the auditory brain stem contribute to cocktail party-deficits

Age-related hearing loss consists of both peripheral and central components and is an increasing global health concern. While peripheral hearing loss is well understood, central hearing loss-- age-related changes in the central auditory pathways resulting in a listeners inability to process sound correctly --remains poorly understood. In this study, we focus on the pathway from the cochlear nucleus to the medial nucleus of the trapezoid body (MNTB), which depends on heavily myelinated axons for microsecond-level temporal precision required for sound localization. Using a combination of auditory brainstem response recordings (ABR), advanced light and electron microscopy, and behavioral testing with prepulse inhibition of the acoustic startle response (PPI) we identified a correlation between oligodendrocyte loss, abnormal myelination in MNTB afferents, altered ABR wave III morphology indicating MNTB dysfunction, and deficits in spatial hearing behaviors in aging Mongolian gerbils. These findings provide a mechanistic explanation of how demyelination contributes to age-related dysfunction in the auditory brainstems sound localization pathway.

neuroscience↗

bioRxiv2022

Identification of different classes of genome instability suppressor genes through analysis of DNA damage response markers

Genetic studies in Saccharomyces cerevisiae have identified 266 genes and predicted an additional 38 genes that suppress the accumulation of spontaneous gross chromosomal rearrangements (GCRs). Here we identified mutations that induce two DNA damage response (DDR) markers, Hug1 expression and Ddc2 foci, and combined these data with other published screens identifying mutations inducing other DDR markers, including Rad52 foci and Rnr3 expression. Together, these data identify four categories of mutations: most mutations were DDR- GCR-, 356 were DDR+ GCR-, 72 were DDR- GCR+, and 157 were DDR+ GCR+. These results indicate that induction of DDR markers alone, while allowing DDR analysis, is not a reliable indicator of increased genome instability. They also guide further analysis of mechanistically distinct groups of GCR-inducing mutations, such as mutations that increase levels of GCR-inducing DNA damage and mutations that result in mis-repair of normal levels of DNA damage resulting in GCRs.

genetics↗

bioRxiv2021

Predicting the Influence of Axon Myelination on Sound Localization Precision Using a Spiking Neural Network Model of Auditory Brainstem

Spatial hearing allows animals to rapidly detect and localize auditory events in the surrounding environment. The auditory brainstem plays a central role in processing and extracting binaural spatial cues through microsecond-precise binaural integration, especially for detecting interaural time differences (ITDs) of low-frequency sounds at the medial superior olive (MSO). A series of mechanisms exist in the underlying neural circuits for preserving accurate action potential timing across multiple fibers, synapses and nuclei along this pathway. One of these is the myelination of afferent fibers that ensures reliable and temporally precise action potential propagation in the axon. There are several reports of fine-tuned myelination patterns in the MSO circuit, but how specifically myelination influences the precision of sound localization remains incompletely understood. Here we present a spiking neural network model of the auditory brainstem with myelinated axons to investigate whether different axon myelination thicknesses alter the sound localization process. Our model demonstrates that axon myelin thickness along the contralateral pathways can substantially modulate ITD detection. Furthermore, optimal ITD sensitivity is reached when the MSO receives contralateral inhibition via thicker myelinated axons compared to contralateral excitation, a result that is consistent with previously reported experimental observations. Our results suggest specific roles of axon myelination for extracting temporal dynamics in ITD perception, especially in the pathway of the contralateral inhibition.

neuroscience↗

bioRxiv2021

Hearing Ability of Prairie Voles (Microtus ochrogaster)

Hearing ability of mammals can be impacted by many factors including social cues, environment, and physical properties of animal morphology. Despite being used commonly to study social behaviors, hearing of the monogamous prairie vole (Microtus ochrogaster) has never been fully characterized. In this study, we measure morphological head and pinna features and use auditory brainstem responses to measure auditory capabilities of prairie voles characterizing monaural and binaural hearing and hearing range. Additionally, we measured unbonded male and female voles to characterize differences due to sex. We found that prairie voles show a hearing range with greatest sensitivity between 8 - 32 kHz, robust binaural hearing, and characteristic monaural ABRs. We show no differences between the sexes for binaural hearing or hearing range, however female voles have increased amplitude of peripheral ABR waves I and II and increased latency of wave IV. Our results confirm that prairie voles have both low and high frequency hearing, binaural hearing, and despite biparental care and monogamy, differences in processing of sound information between the sexes. These data further highlight the necessity to understand sex-specific differences in neural processing that may underly variability in behavioral responses between sexes. HighlightsO_LIMonogamous prairie voles hear across both low and high frequencies. C_LIO_LIFemale prairie voles show differences in monaural hearing compared to males. C_LIO_LIThere is no difference in binaural hearing or pinna/head size morphology between the sexes. C_LI

neuroscience↗