Tachykinin-1-expressing parasubthalamic nucleus neurons are necessary for odorant-induced appetite suppression

Abstract

Odorants play a critical role in regulating feeding behavior by signaling potential threats or food sources in the environment. However, the neural mechanisms by which odorants affect feeding are not well understood. Tachykinin-1-expressing neurons in the parasubthalamic nucleus (PSTN^Tac1 neurons) are critical for reducing food intake in response to internal appetite-suppressing hormones, gastric distension, and external cues that signal danger. Therefore, we tested the hypothesis that activity in these neurons is modulated by exposure to aversive, attractive, and neutral odorants. Using fiber photometry in mice, we found that PSTN^Tac1 neurons increase activity in response to the aversive predator odorants 2-methyl-2-thiazoline (2MT) and 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), but not to neutral or attractive odorants. This activation correlates with a reduction in food intake and an increase in the latency to initiate feeding. Furthermore, chemogenetic inhibition of PSTN^Tac1 neurons blocks the suppression of feeding caused by 2MT and TMT. These findings highlight the specificity of PSTN^Tac1 neurons in processing aversive olfactory signals and their critical role in integrating external threat cues with internal signals that regulate appetite.