Thanks Jonas!

and to alumni and colleagues for valuable feedback and inputs Hanna Hayat, Yaniv Sela, @innaslutsky.bsky.social
@oyiz.bsky.social

🙏

(6/6)

✨ Take-home: LC neurons are not a single unitary arousal system.

LC→PRN brainstem pathway is critical for sound-evoked awakening

Thanks to team 🙌 led by amazing
@nmatosevich.bsky.social , Noa Regev, U. Kimchi, N. Zelinger,
@SinaKabaha Amit Marmelstein @noamgabay.bsky.social

(5/6)

What happens if you silence LC synapses?

Using an optoGPCR (PdCO), we found that shutting down LC→PRN boosts sigma power and deepens NREM sleep. Silencing both PRN + BF was even more effective.

(4/6)

Timing is everything ⏱️

Optogenetic activation showed that sound-evoked awakening depends on which LC neurons are active AND when they fire - synchrony with the sound is key.

(3/6)

Here’s the twist: only the LC→PRN pathway shows a fast NE surge when sounds are played during sleep.

That rapid signal predicts whether the sound will wake the mouse.

(2/6)

Not all LC pathways are the same 👀

We compared LC projections to the basal forebrain (BF) and to the brainstem pontine reticular nucleus (PRN).
They turned out to be partially distinct populations.