A bidirectional network for appetite control in larval zebrafish.

Maxim Nikitchenko,Ji-Yoon Kim,Florian Engert,Chao-Tsung Yang,Misha B Ahrens,Sam Kunes,Deepak Ailani,Owen Randlett,Caroline Lei Wee,Koichi Kawakami,Robert Evan Johnson,Armin Bahl,Erin Yue Song

doi:10.7554/elife.43775

Abstract

Medial and lateral hypothalamic loci are known to suppress and enhance appetite, respectively, but the dynamics and functional significance of their interaction have yet to be explored. Here we report that, in larval zebrafish, primarily serotonergic neurons of the ventromedial caudal hypothalamus (cH) become increasingly active during food deprivation, whereas activity in the lateral hypothalamus (LH) is reduced. Exposure to food sensory and consummatory cues reverses the activity patterns of these two nuclei, consistent with their representation of opposing internal hunger states. Baseline activity is restored as food-deprived animals return to satiety via voracious feeding. The antagonistic relationship and functional importance of cH and LH activity patterns were confirmed by targeted stimulation and ablation of cH neurons. Collectively, the data allow us to propose a model in which these hypothalamic nuclei regulate different phases of hunger and satiety and coordinate energy balance via antagonistic control of distinct behavioral outputs.

Highlights

The regulated intake of food based on caloric needs is a fundamental homeostatically controlled process that is essential for health and survival
A robust readout of food intake in larval zebrafish was obtained both by the ingestion of fluorescently-labeled paramecia and by behavioral analysis, both of which have been adapted for this study (Johnson et al, 2019; Jordi et al, 2015, 2018; Shimada et al, 2012)
We found that artemia exposure caused significant increases in both mLH and lLH activity, whereas little change was detected in caudal hypothalamus (cH) neurons (Figure 4a-c)

Summary

14 ABSTRACT

Medial and lateral hypothalamic loci are known to suppress and enhance appetite, respectively, but the dynamics and functional significance of their interaction have yet to be explored. In larval zebrafish, primarily serotonergic neurons of the ventromedial caudal hypothalamus (cH) become increasingly active during food deprivation, whereas activity in the lateral hypothalamus (LH) is reduced. Exposure to food sensory and consummatory cues reverses the activity patterns of these two nuclei, consistent with their representation of opposing internal hunger states. Baseline activity is restored as food-deprived animals return to satiety via voracious feeding. The antagonistic relationship and functional importance of cH and LH activity patterns were confirmed by targeted stimulation and ablation of cH neurons. The data allow us to propose a model in which these hypothalamic nuclei regulate different phases of hunger and satiety and coordinate energy balance via antagonistic control of distinct behavioral outputs.

INTRODUCTION

61 RESULTS

DISCUSSION

MATERIALS AND METHODS