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bioRxiv · 10.64898/2026.03.03.709382

Parabrachial Ntsr1 neurons modulate food intake and anxiety through a projection to the ventromedial hypothalamus

Pauli, J. L.·Park, S.·Felix, R. R.·Palmiter, R.
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Abstract

The parabrachial nucleus (PBN) is an important hub located in the pons that relays sensory signals from peripheral regions. It is genetically diverse and contains many populations that modulate feeding and responses to threatening situations. A small Ntsr1-expressing population of neurons was identified that projects selectively to the ventromedial hypothalamus (VMH). The Ntsr1 neurons are scattered throughout the lateral PBN with a cluster of cells along the border to the nucleus of the lateral lemniscus (NLL) that overlap with Cck and Foxp2 expression. Chemogenetic activation of PBN Ntsr1 neurons results in Fos induction in Nr5a1 (SF1) and Bdnf neurons in the VMH. Activation of PBN Ntsr1 neurons or their terminals in the VMH reduces food intake after fasting and increases anxiety-like behaviors. In anxiogenic feeding assays, activation of PBN Ntsr1 neurons increases latency to feed as well as reducing food intake. Photometry showed that PBN Ntsr1-neuronal activity increases during anxiogenic situations but is suppressed during food consumption, suggesting a role in threat-induced suppression of feeding. Silencing PBN Ntsr1 neurons with tetanus toxin light-chain increased food intake and reduced anxiety. These findings reveal a genetically defined PBN to VMH circuit that responds to threats and suppresses feeding behavior. SignificanceThis study explored a population of Ntsr1 mRNA-expressing neurons in the parabrachial nucleus (PBN) that project selectively to the ventromedial hypothalamus (VMH). Stimulation of PBN Ntsr1 neurons and their terminals in the VMH decreased feeding and increased anxiety, results that resemble those achieved by activating VMH neurons, implicating the Ntsr1 neurons as part of the circuitry that controls feeding and anxiety. Because PBN Ntsr1 neurons are activated by aversive stimuli, they are posited to help mice suppress feeding in risky environments.

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Pauli, J. L., Park, S., Felix, R. R., Palmiter, R.. 2026-03-05. Parabrachial Ntsr1 neurons modulate food intake and anxiety through a projection to the ventromedial hypothalamus. https://doi.org/10.64898/2026.03.03.709382

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