Having trouble getting the probes or dyes? Contact us at [email protected] — we will be more than happy to help.

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?

(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.

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.

(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.

(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.