The paper is open access in @CellReports!
👉 doi.org/10.1016/j.c...
Huge thanks to co-first authors Luca Nava & Noemi Barsotti, PI @RaffaellaTonini, and the whole multi-institutional team that made this possible. @LabPasqualetti, @Nets3L, @joeycheers.bsky.social. 🙏
(7/7)
These findings position eCB signaling as a dynamic regulator of prefrontal-noradrenergic crosstalk, with broader implications for goal-directed attention, cognitive flexibility, arousal, and related disorders in which this circuit is dysregulated.
(6/7)
eCB signaling at the PFC→LC synapse is key for telling outcomes apart. Optogenetic activation of this connection drives place conditioning in both control mice and mice lacking CB1 receptors in the PFC, yet only controls discriminate between stimulation frequencies.
(5/7)
Under sustained activation, LC neurons mobilize endocannabinoids (eCBs), lipid molecules that act as retrograde negative feedback, weakening the PFC→LC synapse. This limits NE release back in the PFC and constrains PFC neuronal entrainment.
(4/7)
Using optogenetics, electrophysiology, fiber-photometry, and rabies-based tracing, we confirm a direct glutamatergic projection from PFC to LC. Activating it drives NE release and recruits NE-sensitive neuronal activity back in the PFC. A genuine two-way loop.🔄
(3/7)
The locus coeruleus (LC) is the brain's main source of norepinephrine (NE) and is well known to modulate prefrontal cortex (PFC) activity. What remained unclear is how PFC inputs regulate LC output in return, and whether that feedback can be fine-tuned.
(2/7)
Excited to share our new paper out in @CellReports! During my time in Raffaella Tonini lab ( @neuromodlab.bsky.social ) at @iitalk.bsky.social, we uncovered how the brain's prefrontal cortex and locus coeruleus form a reciprocal loop, and how the endocannabinoid system controls it. 🧵