Congrats, Josh and Xiaowei!

Congratulations! Well deserved!

Congrats! Very important work!

(n/n) This work wouldn’t have been possible without the incredible efforts of the entire Sternson Lab (@BrainCaRMA, @ronggong, @vicente-rodriguez.bsky.social) and many others—whose contributions have been invaluable. Special thanks to @hhmi.org and @ucsdmedschool.bsky.social. Thank you for reading!

(10/n) Thanks to Dr. Dana Small for the insightful Science Perspective article on our work www.science.org/doi/10.1126/... www.science.org/doi/10.1126/...

(9/n) In short, our study shows that VTADA neurons encode food palatability at intermediate timescales, sustaining hedonic eating. Precise dopamine release timing is key for controlling the consumption phase, while GLP-1R activation during palatable food intake dampens this dopamine-driven effect

(8/n) We tested semaglutide (Ozempic), with a ramped daily dose to engage satiety pathways. Initially, it shortened feeding bouts and suppressed VTADA responses to palatable food. Yet as the dose increased, VTADA neurons rebounded—driving overconsumption, an effect reversed by targeted inhibition

(7/n) Do VTADA neurons truly sustain hedonic eating? We boosted their activity during feeding and observed a hedonic contrast effect: laser-OFF blocks elicited a negative response, while stimulation significantly prolonged feeding bouts. Conversely, suppressing VTADA neurons reduced bout duration

(6/n) Switching from high- to low-palatability food abruptly reduces feeding and VTADA signals—revealing a “hedonic contrast” effect—while lower-palatability food elicits shorter bout durations and negative DA responses. VTADA neurons may encode food palatability to sustain hedonic eating over time

(5/n) Prior work shows VTADA neurons respond to food cues, reward utility, and post-ingestion, yet how they encode palatability at intermediate timescales remains unclear. We found VTADA neurons remain active throughout palatable food consumption, with their activity scaling to palatability

(4/n) The VTA is diverse—its inhibitory VTAVGAT neurons can suppress VTADA cells. So how do the periLCVGLUT2 neurons fit in? We uncovered a pathway where periLCVGLUT2 neurons activate VTAVGAT neurons, which then dampen VTADA signaling to the nucleus accumbens by reducing dopamine release

(3/n) Our group discovered that the peri‐locus coeruleus (periLC), downstream of hunger centers, plays a key role in promoting hedonic eating via double-negative inhibition. But how exactly does it work? Intriguingly, we identified a direct periLC→VTA pathway that selectively prolongs feeding bouts

(2/n) Hedonic eating means indulging in food for pleasure rather than necessity—think of the “salted-nut phenomenon.” In our study, we offered a highly palatable Ensure alongside a less tasty version and found that the tastier option led to longer feeding bouts, though not more bouts overall