A sync state in the midbrain dopamine network for interoceptive nutrient learning
Xiao Yang1, Weijie Yan2, Weixuan Lu3
1Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Beijing Institute for Brain Research, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing 102206, China; Chinese Institute for Brain Research, Beijing, Beijing 102206, China.
Abstract:
Gastrointestinal nutrient signals, arriving minutes after eating, powerfully reinforce food intake. How the brain links these delayed interoceptive signals to immediate sensory cues remains unclear. We show that ventral tegmental area (VTA) dopamine neurons resolve this credit-assignment problem by entering a distinct network state characterized by synchronized ∼0.8 Hz bursting, extending the integration window for learning across the gut-brain axis. Using two-photon imaging, Neuropixels recordings, and in vivo dopamine sensors in behaving mice, we identify this "sync state" emerging tens of seconds after ingestion begins, when orosensation overlaps with post-ingestive nutrient signals. This activity cannot be explained by reward prediction error or motor signals but predicts learning-dependent enhancement of future cue-evoked consumption vigor. Silencing dopamine neurons during oral-gastric overlap blocks nutrient learning without affecting intake, while optogenetic stimulation mimicking synchrony is sufficient to drive learning without nutrients. These findings reveal a novel dopaminergic mechanism for interoceptive credit assignment.
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