Yulong Li Lab

PKU tags, novel genetically encoded shape tags for cell labeling in light and electron microscopy Distinguishing among neuronal cell types is crucial for deciphering complex neural networks and brain functions. However, the current repertoire of cell-labeling tools compatible with light microscopy...

BioRxiv link
www.biorxiv.org/cgi/content/...

(3/3)Moreover, we showcased the power of PKU tags for in vivo shape-based “barcoding’’ of multiple cell types, delivering high-contrast and easily distinguishable signals in both light and electron microscopy.

(2/3)By integrating self-assembling protein polymers, spectrally distinct fluorescent proteins, and a nuclear targeting motif, PKU tags provide a versatile palette of cell-labeling tools. With combinatorial strategy, the system can theoretically scale to hundreds of patterns.

(1/3)Excited to share PKU tags—our lab’s latest contribution expanding the toolkit for cell-type labeling with a new shape dimension! Developed at PKU, these genetically encoded tools enable multiplex cell-type labeling compatible with both light and electron microscopy.

We’re bringing our latest progress in neuromodulator imaging to #SfN2025! Don’t miss Dr. Li’s talk (Nov 19) and our lab’s posters (Nov 16). We look forward to connecting, exchanging ideas, and exploring collaborations. #neuroscience #neuroimaging #biosensors @sfn.org

Having trouble getting the probes or dyes? Contact us at yulonglilab2018@gmail.com — we will be more than happy to help.

Glad to see Yu Zheng PhD @zheng-yu.bsky.social highlighting the far-red dopamine sensor for multiplex imaging of in vivo neuromodulation. Happy to share these probes to the community.

6/ Sustained serotonin release in vCA1 keeps 5-HT2C–expressing pyramidal neuron ensembles, linking temporally separated events. When the gap exceeds the brain’s “safe window”, brief serotonin release fails to drive these ensembles, thus preventing maladaptive learning.

5/ We mapped molecular specificity in vCA1 using multiplex FISH technique (thanks to Yanyi Huang & Tianyi Chang), and showed that serotonin modulates the associable window via 5-HT2C-expressing pyramidal neurons with CRISPR-Cas9 based gene perturbations.

4/ Using temporally precise optogenetics, we causally linked DRN→vCA1 serotonergic projections to the regulation of the associable interval in trace fear conditioning.

3/ We found that serotonin is the key.
In trace fear conditioning, systemic serotonin manipulations bidirectionally shift the associable interval. Using our 5-HT3.0 sensor, we showed real-time, in vivo evidence that serotonin release patterns in vCA1 tightly track this time window.

2/ The brain needs tight temporal boundaries for associations of cues and threats.
Too narrow → We might miss real threats.
Too wide → We might create false alarms.
The question: What keeps this window just right?

Serotonin shapes the temporal window for associative fear learning Fear learning is a critical adaptive mechanism that enables the association of an environmental cue (the conditioned stimulus, CS) with a potential threat (the unconditioned stimulus, US), even when t...

1/ Excited to share a new preprint!
Our latest study uncovers how serotonin precisely controls the “time window” for fear learning, ensuring that our brains link cues (CS) & threats (US) only when it’s adaptive.
#Neuroscience #FearLearning
www.biorxiv.org/content/10.1...

(3/3) Applying Cort1.0 in vivo: We observed stress-induced 😰CORT elevation in the hypothalamus (e.g., during tail suspension) with Cort1.0 by fiber photometry. Real-time stress hormone readouts, live!

(2/3) Applying Prog1.0 in vivo: We detected both the maternal behavior-associated🤱 and spontaneous PROG signals ☀️🌙in the hypothalamus with Prog1.0 by fiber photometry.

(1/3) Excited to introduce our new GRAB sensors for a series of steroid hormones! These tools enable real-time detection of steroid hormone dynamics in vivo🐭🧠. Happy to share these sensors and welcome any feedback! Please contact yulonglilab2018@gmail.com for information.

Amazing work by Yu Zheng @zheng-yu.bsky.social， Ruyi Cai @ruyic.bsky.social, and the whole team. Huge thanks to our fantastic collaborators: Yu Mu, Zhixing Chen (@zhixingchen2.bsky.social), Luke Lavis,Eric Schreiter, Kai Johnsson, and Jonathan Grimm.

In vivo multiplex imaging of dynamic neurochemical networks with designed far-red dopamine sensors Dopamine (DA) plays a crucial role in a variety of brain functions through intricate interactions with other neuromodulators and intracellular signaling pathways. However, studying these complex netwo...

Excited to share our Science paper on HaloDA1.0-the first genetically encoded far-red dopamine sensor! 🥳It enables powerful multiplex imaging in neurons, brain slices, and live animals.🧠🔬 #GRABsensors #Dopamine www.science.org/doi/10.1126/...

Deepest thanks to @yulonglilab.bsky.social and all those who attended his seminar on GRAB sensors in neuromodulator dynamics hosted by @maximoprado.bsky.social at @westernu.bsky.social.

Big thanks@westernu.bsky.social @westernubrainscan.bsky.social @tridentpct.bsky.social for inviting! Loved presenting our GRAB sensor work and the great discussions. Hope to visit again!

Join the "Genetically-Encoded and Chemigenetic Tools for Analysis and Control of Biological Systems" symposium at #ChemPacific2025! Explore cutting-edge tools alongside other world-class science in Hawaii. 🌴🌴
pacifichem.org

Thrilled to share our latest research published in Nature Communications! Our new GRAB sensor of SNPF promotes discoveries in the dynamics and molecular regulation between neuropeptide and neurotransmitter release in vivo. Check out the full paper here: www.nature.com/articles/s41...

(6/6) Huge thanks to our team Shu Xie @shuxie.bsky.social , Xiaolei Miao and Guochuan Li, et al, for their excellent work!

(5/6) The red ACh sensors reliably detect ACh release in various brain regions, including amygdala, hippocampus, and cortex, providing valuable insights regarding the functional role of the cholinergic system.

(4/6) Through multiplex imaging using 2P microscopy, we've explored the dynamics of ACh and norepinephrine in the visual cortex across various behaviors. rACh1h responds to both water licking and forced running, while NE2m responds only to forced running.

(3/6) With fiber photometry, we've shown the ability to perform multiplex recordings of ACh and dopamine signals during Pavlovian conditioning tasks, and distinct dynamics between ACh and serotonin during REM sleep.

(2/6) These sensors are rationally engineered with a chimeric GPCR strategy, providing a superior signal-to-noise ratio compared to existing green ACh sensors.

Red-shifted GRAB acetylcholine sensors for multiplex imaging in vivo The neurotransmitter acetylcholine (ACh) is essential in both the central and peripheral nervous systems. Recent studies highlight the significance of interactions between ACh and various neuromodulat...

(1/6) Excited to introduce our first generation red acetylcholine sensors! #acetylcholine #GRAB #RedSensors
www.biorxiv.org/content/10.1...

(7/7) Great work by Yu Zheng @zheng-yu.bsky.social Ruyi Cai @ruyic.bsky.social , et al, and huge thanks to all of our amazing collaborators including Yu Mu, Zhixing Chen @zhixingchen2.bsky.social , Luke Lavis @rhodamine110.bsky.social , Eric Schreiter, Kai Johnsson , and Jonathan Grimm.

(6/7) Taken together, HaloDA1.0 provides high versatility for multiplex imaging in cultured neurons, brain slices, and behaving animals, facilitating in-depth studies of dynamic neurochemical networks.