A Bidirectional Network for Appetite Control in Larval Zebrafish

Abstract

14Medial and lateral hypothalamic loci are known to suppress and enhance appetite, respectively, 15 but the dynamics and functional significance of their interaction have yet to be explored. Here 16we report that, in larval zebrafish, primarily serotonergic neurons of the ventromedial caudal 17 hypothalamus (cH) become increasingly active during food deprivation, whereas activity in the 18 lateral hypothalamus (LH) is reduced. Exposure to food sensory and consummatory cues 19 reverses the activity patterns of these two nuclei, consistent with their representation of 20 opposing internal hunger states. Baseline activity is restored as food-deprived animals return to 21 satiety via voracious feeding. The antagonistic relationship and functional importance of cH and 22 LH activity patterns were confirmed by targeted stimulation and ablation of cH neurons. 23Collectively, the data allow us to propose a model in which these hypothalamic nuclei regulate 24 different phases of hunger and satiety and coordinate energy balance via antagonistic control of 25 distinct behavioral outputs. convergence point for the neural and biochemical pathways that underlie this regulatory 30 mechanism. Early studies demonstrated by way of electrical stimulation or lesions that specific 31 hypothalamic regions play important roles in the regulation of appetite. For example, while 32 stimulation of ventromedial hypothalamic loci in rodents and cats reduced feeding, activation of 33 more lateral hypothalamic loci increased both hunting behavior and food intake (Anand and 34 Brobeck, 1951; Brobeck et al., 1956; Delgado and Anand, 1953; Krasne, 1962). Conversely, 35 lateral hypothalamic lesions were found to reduce feeding to the point of starvation, whereas 36 medial hypothalamic lesions resulted in overeating (Anand and Brobeck, 1951; Hoebel, 1965; 37 Teitelbaum and Epstein, 1962). Thus, the lateral and medial hypothalamic regions came to be 38 regarded as "hunger" and "satiety" centers, respectively. 39Recent experiments employing optical and electrophysiological methods have lent 40 support to these early studies. For example, GABAergic neurons in the lateral hypothalamus 41 were observed to be activated during feeding and essential for enhanced food intake during 42 hunger (Jennings et al., 2015; Stuber and Wise, 2016). However, these experiments have 43 examined only subsets of hypothalamic neurons; their activity patterns and function within the 44 context of the entire network remain unknown. This limited view hampers our understanding of 45 the dynamical interactions between the ensemble of brain circuits thought to be important for 46 the initiation, maintenance and termination of food consumption (Sternson and Eiselt, 2017). 48 modulatory regions central to the control of appetite and to shed light on their specific roles and 49 dynamical activity patterns in relation to behavior. Using pERK-based brain-wide activity 50 mapping (Randlett et al., 2015), we first identified neuronal populations that display differential 51 neural a...

Abnormal brain development of monoamine oxidase mutant zebrafish and impaired social interaction of heterozygous fish

“…It has been reported that zebrafish exposed to Trans-2phenylcyclopropylamine (PCPA), a non-selective MAO inhibitor, present increased neuronal death (Jie et al, 2009). Contributions of these hypothalamic systems to behaviors in larval zebrafish have been described, including regulation of feeding (Wee et al, 2019). Additionally, zebrafish swim bladder has been reported to receive serotonergic input (Finney et al, 2006) and mao inhibition is known to affect swim bladder control in zebrafish (Sallinen et al, 2009b), which could have compromised the ability of the larvae to move and seek for food.…”

Experience, circuit dynamics, and forebrain recruitment in larval zebrafish prey capture

“…Neuromodulation could also contribute to the gain control of prey capture behavior observed in this study. The dopaminergic system encodes stimulus valence and regulates motivation Matsumoto and Hikosaka, 2009 ; the noradrenergic locus coeruleus is thought to modulate arousal Carter et al, 2010 ; different parts of the hypothalamus are thought to control a variety of motivational functions like arousal and feeding ( Mahler et al, 2014 ; Wee et al, 2019 ). The central amygdala has recently been shown to control predatory hunting in mice, by increasing capture initiation via the periaqueductal gray ( Han et al, 2017 ), which is homologous to the griseum centrale of zebrafish, and receives input from the habenula ( Olson et al, 2017 ).…”

A single-cell resolution gene expression atlas of the larval zebrafish brain

“…One group of eurydendroid cells projected to the dorsal zone of the periventricular hypothalamus (Figure 4D, cluster 4), an area involved in satiety response (Wee et al, 2019). Strikingly, this brain region was also strongly stained for cfos expression during prey capture behavior (Suppl.…”