Neural Control and Modulation of Thirst, Sodium Appetite, and Hunger

Abstract

The function of central appetite neurons is instructing animals to ingest specific nutrient factors that the body needs. Emerging evidence suggests that individual appetite circuits for major nutrients-water, sodium, and food-operate on unique driving and quenching mechanisms. This review focuses on two aspects of appetite regulation. First, we describe the temporal relationship between appetite neuron activity and consumption behaviors. Second, we summarize ingestion-related satiation signals that differentially quench individual appetite circuits. We further discuss how distinct appetite and satiation systems for each factor may contribute to nutrient homeostasis from the functional and evolutional perspectives.

Figure 1.. Operating Timescale of Distinct Appetite Neurons

(A) Representative neuronal populations that regulate thirst (left), sodium appetite (middle), and hunger (right) visualized with fluorescence reporters. Shown are coronal sections of mouse brain containing individual neural populations (upper panels), and magnified images (lower panels). Scale bars, 50 μm. (B) Temporal relationship between neural stimulation and nutrient consumption. The onset of ingestion upon optogenetic activation of appetite neurons. The x axis shows the time before and after neural stimulation, and the y axis shows nutrient consumption. Stimulation of thirst (left) and sodium appetite (middle) neurons induces rapid consumption. Conversely, hunger neurons (right) drive feeding with a longer latency. Photo-stimulation periods are shaded in blue, and nutrient access is indicated by gray bars. (C) Motivational drive after continuous stimulation of appetite neurons. In the absence of ongoing thirst (left) and sodium appetite (middle) neuron activities, animals do not consume water and sodium, respectively. By contrast, robust food consumption is induced after the termination of hunger neuron stimulation (right). Although AgRP-related homeostatic feeding regulation is a slow process, not all feeding circuits are slow-operating. For example, stimulation of GABAergic neurons in a few brain areas drives acute feeding (Hao et al., 2019; Jennings et al., 2013; Zhang and van den Pol, 2017). Abbreviations are as follows: AgRP, agouti-related protein; ARC, arcuate nucleus; nNOS, neuronal NO synthase; PDYN, prodynorphin; pre-LC, pre-locus coeruleus; SFO, subfornical organ.

Figure 2.. Feed-Forward Regulation of Appetite Circuits

(A) Temporal and persistent feed-forward factors regulating thirst (top), sodium appetite (middle), and hunger (bottom). Thirst circuits are temporally inhibited by liquid gulping through signals derived from the oropharyngeal area, while persistent inhibition stems from the gut based on the osmolality of the ingested fluid. Sodium taste signals arising from the mouth persistently inhibit sodium appetite circuits. Various food-related cues like vision, smell, or taste contribute to temporal inhibition of hunger neurons in the ARC. Persistent modulation of hunger neurons is caused by caloric detection by the gut. (B) Sensory modulations of appetite neurons. Shown are schematic calcium dynamics of thirst (red), sodium appetite (blue), and hunger neurons (green) after oral and intragastric nutrient administration. Each neural population receives unique sets of sensory modulation from the periphery after nutrient ingestion.