210 | Lateral hypothalamic glutamatergic inputs to VTA glutamatergic neurons mediate prioritization of innate defensive behavior over feeding

Neural Circuits and Systems Neuroscience

Author: Maria Flavia Barbano | Email: maria.barbano@nih.gov

M. Flavia Barbano , Shiliang Zhang , Emma Chen , Orlando Espinoza , Uzma Mohammad , Yocasta Alvarez-Bagnarol , Bing Liu , Marisela Morales

1° Integrative Neuroscience Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224
2° Confocal and Electron Microscopy Core, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224

The lateral hypothalamus (LH) has long been implicated in feeding behavior and defense responses by its interactions with distinct brain structures, including the Ventral Tegmental Area (VTA). Emerging evidence indicates that LH-glutamatergic neurons infrequently synapse on VTA-dopamine neurons, but establish multiple synapses on VTA-glutamatergic neurons, mediating innate defensive behavior. Here, we investigate whether LH-glutamatergic inputs to VTA-glutamatergic neurons play a more extensive role in different types of innate behavior. We found that activation of LH-glutamatergic neurons innervating the VTA promoted active avoidance, long-term aversion, and escape attempts. In addition, activation of this LH-glutamatergic pathway to VTA decreased feeding behavior in both sated and food restricted mice. By testing feeding behavior in the presence of a predator, we observed that ongoing feeding behavior was interrupted in food restricted mice, and that this predator-induced decrease in feeding behavior was abolished by VTA photoinhibition of glutamate release from LH-glutamatergic fibers. By VTA specific neuronal genetic ablation, we established that predator-induced decreases in feeding behavior were mediated by VTA-glutamatergic neurons but not by neighboring dopamine or GABA neurons. We uncovered an unanticipated neuronal circuit between LH-glutamatergic inputs to VTA-glutamatergic neurons that plays a role in prioritizing escape instead of fighting, freezing, or feeding.