Biology subjects

Lai, H. M.

Publications and source records attributed to Lai, H. M..

3 recordsLinked to original sources

bioRxiv2025

Cerebellum-Targeted Transcranial Focused Ultrasound Stimulation Modulates Hippocampus Neural Activities

Low-intensity transcranial focused ultrasound stimulation (tFUS) has recently emerged as a promising neuromodulation technique due to its non-invasive nature, ability to penetrate deeply, and high spatial resolution. On the other hand, the cerebellum has attracted new interest as a target for neuromodulation. In this study, we investigated how cerebellum-targeted tFUS could modulate hippocampal neural activity. We found that tFUS at pulse repetition frequency (PRF) as high as 10kHz can effectively activate the cerebellum in vivo. Furthermore, PRF at 10kHz, rather than 1kHz, favored remote inhibition of hippocampus neurons. We found that the neuromodulation at hippocampus was mainly mediated by cerebellum cortex than deep cerebellar nucleus. Furthermore, by cFos expression mapping and phase-amplitude coupling analysis, we showed that the hippocampal response at different PRFs resulted from altered neurodynamic interaction rather than overall activation of engaged brain regions. Our results reveal new potential for cerebellum as a neuromodulation target for hippocampus-related functions.

bioengineering↗

bioRxiv2024

Topologically distinct and equivalent multiple efferent arterioles in the human glomeruli

We revisit the assumption that the human glomerulus consists of a capillary network with one afferent arteriole and only one efferent arteriole. Using three-dimensional tissue imaging, we unambiguously demonstrate the existence of multiple efferent arterioles via total reconstruction of a full human glomerular capillary network. Through graph network analysis, we found these multiple efferent arterioles can be topologically distinct or equivalent with reference to the global glomerular capillary network, and were strategically positioned with respect to the afferent arteriole. We also found the extraglomerular connections between two efferent arterioles may have significant contributions to the redistribution of intraglomerular blood flow. These new findings can provide new paradigms in the regulation and dysfunction of glomerular ultrafiltration, the crosstalk between intra- and extraglomerular factors, and the cross-coupling between nephrons.

pathology↗

bioRxiv2024

INSIHGT: Accessible multimodal systems biology with quantitative molecular phenotyping in 3D

Biological systems are complex, encompassing intertwined spatial, molecular and functional features. However, methodological constraints always limit the completeness of information that can be extracted. Here, we report the development of INSIHGT, a minimally perturbative, accessible and cost-efficient three-dimensional (3D) spatial biology method utilizing superchaotropes and host-guest chemistry. This allows highly multiplexed and multi-modal readout of tissue biomolecules in biological systems up to centimeter scales, permitting radio-histological correlation of phosphorylated alpha-synuclein pathologies in human hemi-brainstem. The homogeneous penetration permits reliable semi-quantitative signals in 3D compared to reference signals. Diverse antigens, mRNA transcripts, neurotransmitters, and post-translational and epigenetic modifications, are well-preserved and visualized. INSIHGT also allows multi-round molecular probing for high-dimensional spatial biology and compatibility with downstream traditional histology. With INSIHGT, we mapped previously undescribed podocyte-to-parietal epithelial cell microfilaments and demonstrated their geodesic clustering in mouse glomeruli, and catalogued sparsely located neurofilament-intensive inclusion bodies in the human cerebellum, and identified NPY-proximal cell types defined by spatial morpho-proteomics in mouse hypothalamus. We anticipate INSIHGT can form the foundations for 3D spatial multi-omics technology development and holistic systems biology studies.

bioengineering↗