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

M. Flavia Barbano, Shiliang Zhang, Emma Chen, Orlando Espinoza, Uzma Mohammad, Yocasta Alvarez-Bagnarol, Bing Liu, Suyun Hahn and Marisela Morales ()
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M. Flavia Barbano: National Institutes of Health
Shiliang Zhang: National Institutes of Health
Emma Chen: National Institutes of Health
Orlando Espinoza: National Institutes of Health
Uzma Mohammad: National Institutes of Health
Yocasta Alvarez-Bagnarol: National Institutes of Health
Bing Liu: National Institutes of Health
Suyun Hahn: National Institutes of Health
Marisela Morales: National Institutes of Health

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract The lateral hypothalamus (LH) is involved in feeding behavior and defense responses by interacting with different brain structures, including the Ventral Tegmental Area (VTA). Emerging evidence indicates that LH-glutamatergic neurons infrequently synapse on VTA-dopamine neurons but preferentially establish multiple synapses on VTA-glutamatergic neurons. Here, we demonstrated that LH-glutamatergic inputs to VTA promoted active avoidance, long-term aversion, and escape attempts. By testing feeding in the presence of a predator, we observed that ongoing feeding was decreased, and that this predator-induced decrease in feeding was abolished by photoinhibition of the LH-glutamatergic inputs to VTA. By VTA specific neuronal ablation, we established that predator-induced decreases in feeding were mediated by VTA-glutamatergic neurons but not by dopamine or GABA neurons. Thus, we provided evidence for an unanticipated neuronal circuitry between LH-glutamatergic inputs to VTA-glutamatergic neurons that plays a role in prioritizing escape, and in the switch from feeding to escape in mice.

Date: 2024
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DOI: 10.1038/s41467-023-44633-w

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