Lateral Hypothalamic Glutamate and GABA Neurons Cooperatively Shape Striatum-Wide Dopamine Dynamics During Consumption

Abstract

The lateral hypothalamic area (LHA) contains GABAergic and glutamatergic neurons that converge on the midbrain dopamine system and exert opposing influences on consummatory feeding behavior. However, the activity dynamics of these populations during consumption and their impact on striatal dopamine release remain poorly understood. Here, we show that LHA GABAergic and glutamatergic neurons independently scale their activity during the consumption of rewarding and aversive solutions while cooperatively regulating dopamine release along the anterior-posterior axis of the striatum in mice. Dopamine release exhibited widespread modulation during consumption, with anterior striatal regions showing stronger representation of solution value and its recent history--an effect dependent on LHA activity. These findings suggest that the LHA acts as a central regulator of striatal dopamine release during consumption, providing a mechanism through which hypothalamic circuits influence motivational and consummatory behaviors.