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Other key contributors to this work include Anam Islam, Emir Malovic, Bisma Afzal, and Huaibo Zhang.

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This work was led by @jamunatandukar.bsky.social in the @gaogroupuic.bsky.social in the @uicbios.bsky.social and @uic-chemistry.bsky.social and was completed in collaboration with Dr. Subhash Pandey's lab at the UIC College of Medicine.

Future efforts will involve characterizing the genes targeted by increased m6A levels, as well as structural and functional analyses of the neurons and circuits within the affected brain regions.

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They further underscore the necessity of high-resolution spatial omics methods to study epitranscriptomic regulations under neurological conditions in a cell-specific manner.

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These results suggest that prolonged adolescent alcohol exposure can increase Mettl3 expression in a neuron-specific and brain-region-specific manner, triggering epitranscriptomic changes in the affected neurons.

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In contrast, we observed no significant changes across neurons, astrocytes, or microglia within the basolateral amygdala or the hippocampal CA3, which neighbor the above regions.

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In short, we observed a significant increase in cytoplasmic Mettl3 mRNA selectively in neurons, but not in astrocytes or microglia, within the central amygdala and the CA1 and dentate gyrus of the hippocampus in adult brains after adolescent alcohol exposure.

The methodological advantages of this approach facilitated a highly specific and precise analysis of Mettl3 mRNA across distinct cell types (neurons, astrocytes, and microglia) and critical brain regions (amygdala and hippocampus).

Named RESOLVE-FISH, we used this 3D spatial transcriptomics method to quantify mRNA copy numbers with single-cell resolution and single-molecule sensitivity.

we employed a super-resolved, 3D spatial transcriptomics approach to map Mettl3 expression following adolescent intermittent alcohol exposure in a cell-type- and brain-region-specific manner.

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that catalyzes N6-methyladenosine (m6A) RNA modification, in the central amygdala and other critical brain regions responsible for emotion and memory processing (Malovic et al., Neuropharmacology 2025),

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Building on our recent study with Dr. Subhash Pandey's lab (UIC Department of Psychiatry) identifying the upregulation of METTL3, a key epitranscriptomic "writer"

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Recent studies have found increasing evidence connecting epitranscriptomic changes in the brain and alcohol exposure.

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Epitranscriptomic regulation is a cellular process that involves biochemical modifications of RNA molecules after they are transcribed. These modifications affect mRNA stability and translation efficiency downstream, thereby influencing gene expression patterns within the cell.

In our latest preprint, we explore these questions through the lens of the epitranscriptomics: www.biorxiv.org/content/10.6...

biorxiv.org

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Reto Fiolka @retof.bsky.social · 27/01/2026

Have you wondered how alcohol affects your emotions and behavior in the long run? How does (excessive) alcohol exposure trigger changes in the brain at the molecular, cellular, and circuitry levels?

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Reposted by Ruixuan Gao

We have two funded postdoctoral positions available. Topics encompass: -Next gen light-sheet fluorescence microscopy instrumentation -Structured illumination microscopy and other approaches to extend the resolution limit. -Nonlinear microscopy combined with adaptive optics / phase conjugation

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Reposted by Ruixuan Gao

FocalPlane @focalplane.bsky.social · 02/12/2025

🔬🔦Check out our ‘Imaging spotlight’ on Volumetric Imaging via Photochemical Sectioning (VIPS) from @ruixuan3.bsky.social, Srigokul Upadhyayula and colleagues. VIPS helps researchers scale super resolution imaging to large whole-mount tissues. focalplane.biologists.com/2025/12/02/i...

focalplane.biologists.com

Imaging spotlight: Volumetric Imaging via Photochemical Sectioning (VIPS) - FocalPlane

Imaging spotlight: Volumetric Imaging via Photochemical Sectioning (VIPS) - Tools

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Reposted by Ruixuan Gao

Gokul Upadhyayula @supgokul.bsky.social · 17/10/2025

Thrilled to share our Science cover! VIPS (volumetric imaging via photochemical sectioning) eliminates working-distance limits for whole-mount, nanoscale imaging. LLSM + photodegradable hydrogel + petabyte-scale compute → mapped axons & myelin across two mouse olfactory bulbs (WT vs NPC1).

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Reposted by Ruixuan Gao

Science Magazine @science.org · 16/10/2025

A new method called VIPS enables organ-wide nanoscale reconstruction for quantitative mapping of connectivity and molecular landscape in intact tissue. Learn more this week in Science: scim.ag/4n4GKPm

This three-dimensional rendering of a mouse olfactory bulb exposes axons and myelin sheaths, the neuronal wiring that transmits odor information.

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(14/x) Finally, we extend our sincere gratitude to the editor, reviewers, collaborators, and colleagues for their time and insightful feedback to this manuscript

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(13/x) With the potential for large AI models to unlock and make image analysis and data mining more accessible, we anticipate VIPS will uncover biologically meaningful insights from petabyte-scale or even larger nanoscale resolution imaging datasets

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(12/x) VIPS is compatible with various tissue types and labeling strategies, including sparse (e.g., immunofluorescence, FPs) and dense labels. Specifically with the latter, VIPS could form the optical foundation for synaptic-level dense connectome of whole brains

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(11/x) This proof-of-concept study highlights the potential of VIPS to advance spatial biology research across various biological domains - from studying biological stereotypy to investigating disease perturbations across whole organs or organisms at subcellular resolution

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GitHub - abcucberkeley/PetaVIPS

(10/x) Petabyte-scale image processing and olfactory-bulb-wide axon/myeline/tractography analysis with PetaKit5D and PetaVIPS (github.com/abcucberkele...) revealed distinct spatial patterns of axon degeneration and de-/dysmyelination in the neurodegenerative mouse

github.com

Contribute to abcucberkeley/PetaVIPS development by creating an account on GitHub.

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(9/x) Using light-sheet photochemical sectioning and on-block lattice light-sheet microscopy (LLSM), we imaged two complete adult mouse olfactory bulbs at nanoscale resolution, generating more than a petabyte of data

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(8/x) Two modes of photochemical sectioning are possible: (a) complete degradation of the target volume (“photodegradation”) or (b) cross-sectional sectioning and lift-off of the overlaying volume (“photoslicing”). Option b preserves the sectioned volume (image: photoslicing)

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(7/x) We then validated spatially confined photochemical sectioning of intact biological specimens embedded in this hydrogel using single- or multiphoton illumination

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(6/x) To implement VIPS, we designed and synthesized a photodegradable superabsorbent hydrogel with a custom photocleavable cross-linker (“PC”) that undergoes complete photo-decimation under UV illumination

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(5/x) However, these techniques often lead to sample distortion, tearing, and loss with hydrogel-embedded specimens, which escalate computational challenges for tera- to petavoxel datasets

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(4/x) Previously, physical sectioning techniques, such as mechanical sectioning and surface ablation, have been combined with on-section or block-face imaging to perform volumetric electron and fluorescence microscopy

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(3/x) In more detail, conventional volumetric fluorescence imaging is constrained by a resolution/imaging depth/sample size trade-off. VIPS overcomes the microscope’s working distance limitation using iterative photochemical sectioning and on-block optical imaging

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(2/x) In essence, VIPS uses a ray or sheet of light to perform spatially precise sectioning of large biological samples, such as a brain. By iteratively repeating this light-based sectioning and imaging, we can achieve volumetric optical imaging of virtually any sample size

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