Lateral hypothalamic control of the striatal dopamine landscape during consummatory behavior.

Abstract

The lateral hypothalamic area (LHA) contains γ-aminobutyric acid (GABAergic) and glutamatergic neurons that converge on midbrain dopamine circuits, exerting opposing control over feeding and reinforcement. How these neurons behave during consummatory behavior and how they shape dopamine release across the striatum remains unresolved. Here, we show that LHA GABAergic and glutamatergic neurons independently scale their activity as mice consume rewarding and aversive solutions and that their balance sets a spatially organized dopamine landscape along the striatum's anterior-posterior axis: anterior regions track solution value and recent history, posterior regions encode sensorimotor features, and release at each site is controlled locally rather than propagated across subregions. This landscape tracks LHA activity, depends on it causally, and reinforces licking initiation. These results position the LHA as a central regulator of a striatum-wide dopamine landscape during consumption, providing a circuit-level framework for how the hypothalamus shapes motivated behavior.