Translucence Biosystems presents at the Society for Neuroscience's 50th Annual Meeting

by Damian Wheeler
November 10, 2021

Translucence Biosystems is honored to present at the Society for Neuroscience's 50th Annual Meeting. Our presentation is entitled, "Brain-wide cellular resolution snapshots of neuronal activity with Npas4 and cFos". Access our presentation materials below.


Recent advances in optical clearing and light sheet imaging have opened an exciting new avenue for brain-wide, cellular resolution immunostaining at the forefront of a dimensional shift from 2D to 3D histology. Providing access to the intricate anatomy of the whole intact brain, new tissue clearing methods can provide neuroscientists with unbiased and complete pictures of brain anatomy and function. With our optimized iDISCO-based clearing methods and our Mesoscale Imaging System for the ZEISS Lightsheet Z.1 microscope, we can image entire mouse brains in ~25 min. Further, our machine learning-enabled 3TK software identifies individual cells throughout the brain and aligns them to the Allen Reference Atlas to produce a regionalized read-out of cellular patterns across 100’s of brain areas. We have applied this technology to generate cellular resolution maps of neuronal activity by measuring the immediate-early gene (IEG) products Npas4 and cFos. Expression of cFos is driven by Ca 2+ - signaling downstream of neuronal activity and is commonly used to mark active neurons. However, cFos expression is also driven by cAMP elevations and signaling pathways engaged by neurotrophins or other paracrine factors. In contrast, Npas4 expression is neuron-specific and tightly tuned to Ca 2+ -dependent signaling pathways. Using our Npas4 recombinant rabbit monoclonal antibody and a commercial cFos antibody, we developed whole-brain co-staining procedures and performed experiments on mice kept in the dark and exposed to light for various periods of time. After 24 hours in the dark, we found a large number of cFos(+) neurons, yet these same neurons did not express Npas4, suggesting that factors other than neuronal activity per se drove cFos expression at baseline. After light exposure, the lower baseline expression of Npas4 supported a much larger fold-change increase in expression than with cFos, where the elevated baseline of cFos(+) cells masked the precise identification of the stimulus-related ‘trace’. The fidelity of the Npas4 response allowed our statistical anatomics tools to identify a large number of brain regions, some expected and some not, that had elevated neuronal activity after light exposure. Similarly, in Contextual Fear Conditioning experiments, home cage mice expressed much less Npas4 than cFos, allowing for more precise monitoring of changes in neuronal activity after context exposure and shock. Our pipeline for brain-wide monitoring of cFos and Npas4 expression allows for high-fidelity monitoring of neuronal activity with Npas4 and also allows for mapping responses to GPCRs or trophic factors by measuring cFos(+)/Npas4(-) neurons.

Access the presentation file here.

Ask your question

Send us your questions and we will get back to you as soon as possible

Thank you! Your submission has been received!
Something went wrong while submitting the form.
Please, contact via us direct email info@translucencebio.comand

Recent news

June 30, 2021

Celebrating the Fourth with Neuroscience Fireworks

Credit for this work goes to an NIH-supported team that includes Ricardo Azevedo and Sunil Gandhi, at the Center for the Neurobiology of Learning and Memory, University of California, Irvine, and their collaborator Damian Wheeler, Translucence Biosystems, Irvine, CA. Azevedo is also an NIH National Research Service Award fellow and a Medical Scientist Training Program trainee with Gandhi.
Damian Wheeler
June 15, 2021

Translucence Biosystems presents at the 7th Annual BRAIN Initiative Investigators Meeting

Translucence Biosystems is honored to present at the 7th Annual BRAIN Initiative Investigators Meeting. Our presentation is entitled, "Measurement of Npas 4 and cFos for Brain-Wide Snapshots of Neuronal Activity" Access our presentation materials below.
Damian Wheeler
June 7, 2021

On the forefront of 3D histology | Translucence Biosystems featured in CALIT2’s Interface Magazine

The California Institute for Telecommunications and Information Technology at the University of California, Irvine Fall 2019 issue covers transformational tools. The article features the Mesoscale Imaging System™, developed by then Graduate Student in the dual M.D./Ph.D. program University of California, Irvine, Ricardo Azevedo and Associate Professor, Sunil Gandhi, Ph.D.
Damian Wheeler