Parabrachial <i>Ntsr1</i> neurons modulate food intake and anxiety through a projection to the ventromedial hypothalamus.

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 <i>Ntsr1</i>-expressing population of neurons was identified that projects selectively to the ventromedial hypothalamus (VMH). The <i>Ntsr1</i> neurons are scattered throughout the lateral PBN with a cluster of cells along the border to the nucleus of the lateral lemniscus that overlap with <i>Cck</i> and <i>Foxp2</i> expression. Chemogenetic activation of PBN <i>Ntsr1</i> neurons results in <i>Fos</i> induction in <i>Nr5a1</i> (SF1) and <i>Bdnf</i> neurons in the VMH. Activation of PBN <i>Ntsr1</i> neurons or their terminals in the VMH reduces food intake after fasting and increases anxiety-like behaviors. In anxiogenic feeding assays, activation of PBN <i>Ntsr1</i> neurons increases latency to feed as well as reducing food intake. Photometry showed that PBN <i>Ntsr1</i>-neuronal activity increases during anxiogenic situations but is suppressed during food consumption, suggesting a role in threat-induced suppression of feeding. Silencing PBN <i>Ntsr1</i> 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.