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Identifying neuronal cell types and their biophysical properties based on their extracellular electrical features is a major challenge for experimental neuroscience and for the development of high-resolution brain-machine interfaces. One example is identification of retinal ganglion cell (RGC) types and their visual response properties, which is fundamental for developing future electronic implants that can restore vision.The electrical image (EI) of a RGC, or the mean spatio-temporal voltage footprint of its recorded spikes on a high-density electrode array, contains substantial information about its anatomical, morphological, and functional properties. However, the analysis of these properties is complex because of the high-dimensional nature of the EI. We present a novel optimization-based algorithm to decompose EI into a low-dimensional, biophysically-based representation: the temporally-shifted superposition of three learned basis waveforms corresponding to spike waveforms produced in the somatic, dendritic and axonal cellular compartments.The decomposition was evaluated using large-scale multi-electrode recordings from the macaque retina. The decomposition accurately localized the somatic and dendritic compartments of the cell. The imputed dendritic fields of RGCs correctly predicted the location and shape of their visual receptive fields. The inferred waveform amplitudes and shapes accurately identified the four major primate RGC types (ON and OFF midget and parasol cells) substantially more accurately than previous approaches.These findings contribute to more accurate inference of RGC types and their original light responses based purely on their electrical features, with potential implications for vision restoration technology.
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http://dx.doi.org/10.1088/1741-2552/ade344 | DOI Listing |
Nat Biomed Eng
September 2025
Department of Computer Science and Engineering, The Hong Kong University of Science and Technology, Hong Kong SAR, China.
The generalization ability of foundation models in the field of computational pathology (CPath) is crucial for their clinical success. However, current foundation models have only been evaluated on a limited type and number of tasks, leaving their generalization ability unclear. We establish a comprehensive benchmark to evaluate the performance of off-the-shelf foundation models across six distinct clinical task types, encompassing a total of 72 specific tasks.
View Article and Find Full Text PDFBiomaterials
August 2025
State Key Laboratory of Eye Health, School of Ophthalmology & Optometry, Eye Hospital, Wenzhou Medical University, 270 Xueyuan Xi Road, Wenzhou, 325027, China; Zhejiang Key Laboratory of Key Technologies for Visual Pathway Reconstruction, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, Ch
Neuroinflammation microenvironment and retinal ganglion cell (RGC) apoptosis are two critical barriers to axonal regeneration following traumatic optic neuropathy (TON). To overcome these challenges, we developed an innovative dual drug delivery strategy utilizing oriented porous nanofiber (OF) and ciliary neurotrophic factor (CNTF)-loaded delivery systems, aiming to promote axonal regeneration and restore RGC survival. Cerium oxide nanoparticles (Ce NPs) were physically mixed with poly(L-lactic acid)/polycaprolactone (PLA/PCL) solution to prepare oriented porous nanofibers (OF-Ce) via electrospinning and solvent evaporation techniques.
View Article and Find Full Text PDFFront Cell Neurosci
August 2025
Department of Neurosurgery, Stanford University, Stanford, CA, United States.
At least 20 distinct retinal ganglion cell (RGC) types have been identified morphologically in the primate retina, but our understanding of the distinctive visual messages they send to various targets in the brain remains limited, particularly for naturalistic stimuli. Here, we use large-scale multi-electrode recordings to examine how multiple functionally distinct RGC types in the macaque retina respond to flashed natural images. Responses to white noise visual stimulation were used to functionally identify 936 RGCs of 12 types in three recordings.
View Article and Find Full Text PDFNeuron
August 2025
Department of Ophthalmology, School of Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Physiology, Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA, USA. Electronic address:
Recent transcriptomic studies have categorized mouse retinal ganglion cells (RGCs) into 45 types; however, little is known about their spatial distributions on the two-dimensional retinal surface and how their local microenvironments impact their functions. Here, we optimized a workflow combining imaging-based spatial transcriptomics (multiplexed-error robust fluorescent in situ hybridization [MERFISH]) and immunostaining on retinal flatmounts. We computationally registered the somata distributions of all RGCs and found that 34/45 molecularly defined types exhibited non-uniform distributions.
View Article and Find Full Text PDFNat Biomed Eng
August 2025
Department of Biomedical Sciences and Tung Biomedical Sciences Centre, College of Biomedicine, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
Characterizing the protospacer adjacent motif (PAM) requirements of different Cas enzymes is a bottleneck in the discovery of Cas proteins and their engineered variants in mammalian cell contexts. Here, to overcome this challenge and to enable more scalable characterization of PAM preferences, we develop a method named GenomePAM that allows for direct PAM characterization in mammalian cells. GenomePAM leverages genomic repetitive sequences as target sites and does not require protein purification or synthetic oligos.
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