Jeff Markowitz

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...

𝗦𝗽𝗼𝗻𝘁𝗮𝗻𝗲𝗼𝘂𝘀 𝗯𝗲𝗵𝗮𝘃𝗶𝗼𝗿 𝗶𝘀 𝗮 𝘀𝘂𝗰𝗰𝗲𝘀𝘀𝗶𝗼𝗻 𝗼𝗳 𝘀𝗲𝗹𝗳-𝗱𝗶𝗿𝗲𝗰𝘁𝗲𝗱 𝘁𝗮𝘀𝗸𝘀
More hidden markov models for cool behaviors and brain data
#neuroskyence
doi.org/10.1016/j.ne...

Thanks Ariel, excited to get this out into the world!

This work was driven by the singular vision and dedication of Zeynep Ulutas, @ezeyulu00.bsky.social . We could not have finished this without @amartyapradhan.bsky.social . @dkoveal.bsky.social provided key guidance on chemistry.

We’re pumped about the future of this technique and are excited to share it with the community. There’s still a lot to optimize, but we’d like to optimize it with you! Seriously, reach out to us, we're nice!

We built a dataset with 100,000(ish) automatically labeled frames. Since the labels are localized through fluorescence, no labeling ambiguity! Turns out: with this many frames you can train techniques like SLEAP and DLC to label body parts with close to sub-mm precision.

We figured out another cool trick. Markerless trackers require labeling of hundreds of frames (click, click, rinse & repeat 500 times). We worked out a machine learning pipeline to take data where we fluorescently tagged 10 body parts and automatically labeled all frames without human intervention.

We successfully targeted the fatty tissue beneath the skin and even into the knee joint! Both of these were readily resolvable with off-the-shelf cameras. If you’re handy, you can pluck out the IR filter in your cameras and try it yourself.

We hit our first hurdle. Standard particle mixtures diffused away within 48 hours. So we formulated alternatives, and now we can watch the insides of mice glow for months as they freely move! We call the end-result Quantum Dot-based Pose estimation in vivo or…QD-Pi (pun intended).

With the first person in the lab, @ezeyulu00.bsky.social , we came up with the idea of injecting near-infrared-fluorescent nanoparticles to make little orbs of light inside the body that we could see from the outside.

Markerless trackers like DLC, SLEAP, DANNCE, Lightning Pose, and others have totally revolutionized tracking movement, since they don’t require the mice to wear anything. BUT, their precision is generally not as good as marker-based methods.

Unlike Mr. Serkis, mice don’t like the suit, and they don’t like anything being attached to their skin. And even if you did manage to get something onto/into the skin, they have lots of fatty tissue, which makes their gelatinous bodies hard to track from the “outside-in”.

GIF by Cinecom.net - Find & Share on GIPHY Discover & share this GIF by Cinecom.net with everyone you know. GIPHY is how you search, share, discover, and create GIFs.

If we want to understand movement, we have to track it. In people, we can look like Andy Serkis and wear a Styrofoam ball bedazzled swimsuit.

High-resolution in vivo kinematic tracking with customized injectable fluorescent nanoparticles Injectable fluorescent nanoparticles were used to track positions on and inside of freely moving animals at high resolution.

Our first preprint has been accepted for publication www.science.org/doi/10.1126/... !!
tldr: @ezeyulu00.bsky.social , @amartyapradhan.bsky.social , @dkoveal.bsky.social and I developed a method using injectable nanoparticles to turn mice into…constellations in motion. 🧵⤵️

A Chemically Stable Photocaged Noradrenaline Photoactivatable neurotransmitters provide spatiotemporally precise experimenter control over endogenous receptor activation in living tissue. The resulting optical stimulus-neuronal response relationship provides a sensitive assay that can drive quantitative studies into receptor signaling. Here, we report a photocaged derivative of the prominent catecholamine neurotransmitter noradrenaline (NA). Appending a carboxynitroveratryl (CNV) caging group to the 4-hydroxyl of the catechol group produced CNV-NA, which displays good aqueous solubility and chemical stability. We verified CNV-NA’s lack of activity at α1B- and β2-adrenoreceptors expressed in HEK cells using a live-cell cAMP assay. We validated CNV-NA photoactivation at native α2-adrenoreceptors in brain slices of rat locus coeruleus using whole cell electrophysiological recordings. Monitoring the stereotyped outward current response to repeated CNV-NA photoactivation revealed that the neuropeptide substance P suppresses α2-adrenoreceptor signaling in locus coeruleus neurons. This work adds a new reagent to the growing library of photocaged neuroactive ligands, thereby expanding the scope and applications of photopharmacology.

another new reagent from the lab! pubs.acs.org/doi/10.1021/...

Dopaminergic action prediction errors serve as a value-free teaching signal - Nature Dopaminergic action prediction error signals are used by mice as a value-free teaching signal to reinforce stable sound–action associations in the tail of the striatum.

Impressive study in @nature from my colleague Marcus Stephenson-Jones at UCL in the @sainsburywellcome.bsky.social

www.nature.com/articles/s41...

Very honored to be awarded tenure officially this week.

SO grateful to my amazing lab, and to mentors, sponsors, and friends who played an absolutely essential part in this.

Striatal dopamine represents valence on dynamic regional scales Adaptive decision making relies on dynamic updating of learned associations where environmental cues come to predict valenced stimuli, such as food or threat. Cue-guided behavior depends on a network ...

Our latest! We measure dopamine signals as rats disambiguate cues that predict reward or threat. We find that dopamine flexibly tracks the changing salience and value of cues, but according to region-specific scales, rapid within-trial dopamine fluctuations prioritize different stimulus features.

And that's a wrap on #InterfaceNeuroGT!

Thank you to the organizers and attendees for a great meeting. See you next year at @riceneuro.bsky.social!

@crozell.bsky.social @vulcnethologist.bsky.social @gtresearchnews.bsky.social

The final #InterfaceNeuroGT session covered joint modeling of brain and behavior. Speakers highlighted how they're using innovative computational and experimental approaches to understand how neural activity influences behavior and intention.

Chaired by @vulcnethologist.bsky.social.

A spatial code governs olfactory receptor choice and aligns sensory maps in the nose and brain Although topographical maps organize many peripheral sensory systems, it remains unclear whether olfactory sensory neurons (OSNs) choose which of the ~1100 odor receptors (ORs) to express based upon t...

Maps are everywhere in the brain...and finally we've discovered one in the nose! Led by @davidhbrann.bsky.social, we uncovered the logic that specifies the positions of each of the 1,000 sensory neuron subtypes in the nose and aligns their projections to the brain.👇👃see more details below👃👇

InterfaceNeuro was a great meeting! There is such an impressive range of technologies being developed for neuromodulation and brain-computer interfaces. It was nice to see this work presented alongside more basic science efforts to figure out exactly what/where we should be modulating.

Wrote a review with some thoughts about dopamine's role in movement. Hope people find it useful and/or stimulating! Thanks again to @bensaunders.bsky.social for the invitation and editing this issue. kwnsfk27.r.eu-west-1.awstrack.me/L0/https:%2F...

Exciting new results from the lab -- *visual* receptive fields in motor and cingulate cortex! Great work from Tony Lien 🧠🧪

Cosyne 2025 - Session 9: Building blocks of cognition YouTube video by Cosyne Talks

My talk at COSYNE is up: "Discrete actions are a unit of both behavior and evolutionary selection" with @akautt.bsky.social and @dattalab.bsky.social www.youtube.com/live/Y8Ke6HC...

Excited to present the latest from the lab out today in Cell www.cell.com/cell/fulltex.... See Thread! 1/8

Picture of Nature article, published 19 Feburary 2025, titled "An opponent striatal circuit for distributional reinforcement learning", with authors Adam S. Lowet, Qiao Zheng, Melissa Meng, Sara Matias, Jan Drugowitsch & Naoshige Uchida.

Excited that Adam Lowet's PhD work has been just been published in @nature.com at doi.org/10.1038/s415.... He has already posted about it on Twitter/X (see twitter.com/Adam_Lowet/s...), but let me re-post his thread here. 1/9

Our new paper on distributional reinforcement learning.

Connectomic analysis of taste circuits in Drosophila - Scientific Reports Scientific Reports - Connectomic analysis of taste circuits in Drosophila

Amidst all the terrible things, it's nice to have some good news - our paper on the architecture of fly taste circuits is published now! Led by Emory undergrad Sydney Walker and grad student Marco Peña Garcia.
Paper here: www.nature.com/articles/s41...
Summary here: devinenilab.org/news/connect...

Cortical control of innate behavior from subcortical demonstration Motor control in mammals is traditionally viewed as a hierarchy of descending spinal-targeting pathways, with frontal cortex at the top. Many redundant muscle patterns can solve a given task, and this...

(1/11) Today I preprinted a lot of work from my postdoc with @dudman.bsky.social, which started with a question of how the nervous system balances flexibility with efficiency of learning. The thread below gives some background....
www.biorxiv.org/content/10.1...