Vinny Costa

Bellair’s? Jealous you get to check that off the bucket list.

Reach out, happy to help get your lab started using the RMAs.

Should work in marmosets if Fc receptor genetic overlap is high enough. Actually given smaller brain volume & higher neuronal density/mm I bet you would get even higher SNR, similar (rhesus brain is too damn big). But probably best to optimize to each species.

Thanks Eliza!

This. is. amazing.

Thanks Lauren!

You can also order the constructs from @uncneurotools.bsky.social where the plasmids are banked.

For NHP users this is our go-to-core because of their extra purification step when producing constructs for NHPs. Give them your business!

Thanks Rachel!

All of the constructs are available on @addgene.bsky.social. If you are interested in using these tools please reach out to @jerzyszablowski.bsky.social and I. I very much want these tools to be used by the NHP community to lower barriers to adopting and molecular and genetics tools in NHPs.

So we now have a tool for monitoring gene expression in vivo from multiple brain regions and cell types simultaneously that predicts ex vivo expression.

As we allude to in the paper RMAs open up a new set of opportunities for behavioral & translational neuroscience in NHPs & eventually humans.

So we could use RMAs to monitor in vivo gene expression but could we also use them to predict ex vivo transduction levels? Turns out, yes!! The peak RMA signal predicts the strength of ex vivo expression!

Could we track Cre-Lox recombination within amygdala neurons in realtime with weekly blood draws? Yes!!! And the timing differed from a non-Cre dependent NHP-RMA

So Jerzy and Sin designed a CRE-dependent NHP-RMA and we injected into the amygdala alongside a Cre-dependent chemogenetic AAV after we injected a retrograde AAV into the nucleus accumbens to deliver Cre to those neurons.

McKenna Romac, a technician in my lab at ONPRC and now a graduate student at Emory, and I were in the middle of doing circuit specific chemogenetic experiments at the time. We wondered if we could use the NHP-RMAs to monitor in vivo Cre-Lox recombination within amygdala circuitry.

And even more exciting was that there was >90% overlap between the macaque and human Fc receptor. So if we could develop it further there was really translational potential.

This never happens. System neuroscience tools developed for use in rodents are notoriously difficult to get to work in nonhuman primates. This worked because Jerzy and Sin had rationally designed RMAs.
Despite only ~60% genetic overlap between the macaque and mouse Fc receptor we had a new tool.

We showed dose dependent reverse transcytosis from the brain to the bloodstream of the NHP-RMA protein being able to read it out in as little as 2 hours!

Because my lab was located at a @nprcnews.bsky.social we had resources to move fast and within months Jerzy and Sin had redesigned a version of the RMA protein for IG1 Fc receptor in primates they called, NHP-RMAs. We injected the protein into the brain and O.M.G it worked inspiring this tweet.

I saw their preprint back in 2022 and was blown away by the potential of this technique. So I of course slid into Jerzy’s DMs on Twitter and said we have to try this in NHPs.

Engineered serum markers for non-invasive monitoring of gene expression in the brain - Nature Biotechnology Gene expression in the mouse brain is measured with a simple blood draw.

Jerzy & his grad student Sangsin Lee designed serum markers called “release markers of activity (RMAs)”. RMAs are secreted by neurons, undergo reverse transcytosis through the BBB, and contained a luciferase reporter that could be read out with a simple blood test. www.nature.com/articles/s41...

Monitoring gene expression in the brain with a simple blood test?

In collaboration with @jerzyszablowski.bsky.social & his lab we figured out how to do it nonhuman primates using noninvasive neuroengineering of synthetic serum markers.

nam11.safelinks.protection.outlook.com?url=https%3A...

A recent paper in @natureportfolio.nature.com raised concerns about the lesion network mapping method. Our team of 16 coauthors analyzed >1000 lesions and 34 symptoms and found that "The methodological foundations of lesion network mapping remain sound" www.biorxiv.org/content/10.6...

It's also worth saying that this is one of the hardest lessons I learned as a new PI: Maintenance is real! Projects are easy to start and hard to hand off. Technology that changes fast accelerates obsolescence. I think there's real value in trying ideas, letting some fail, and moving on. 1/n

Within app purchases include an ascot, pipe, and chalk dust.

"Your h-index will thank you" 😂 The professor's answer to students using Einstein has arrived www.professorfeynman.com

“Students rated your digital twin 0.3 points higher on evals.”

Dopamine Supports Reward Prediction to Shape Reward-Pursuit Strategy Reward predictions not only promote reward pursuit, they also shape how reward is pursed. Such predictions are supported by environmental cues that signal reward availability and probability. Such cue...

🚨📃New Wassum Lab Paper 📃🚨

Out today, Melissa Malvaez, Nick Griffin, Andrea Suarez & team discovered that dopamine can enable reward predictions to shape how we pursue reward.

Surprisingly, we find that dopamine can constrain instrumental reward seeking.

www.jneurosci.org/content/46/8...

🧵👇🏻

Has anyone else had so much negative emotion attached to a project you can't physically bring yourself to work on it

NYU's Center for Neural Science is seeking a faculty candidate that would be jointly appointed with our Tandon School of Engineering. We are looking for post-doc applicants with neuroengineering or computational backgrounds.

apply.interfolio.com/182074