Abstract
The hypothalamic arcuate nucleus (Arc) is a central unit that controls the appetite through the integration of metabolic, hormonal, and neuronal afferent inputs. Agouti-related protein (AgRP), proopiomelanocortin (POMC), and dopaminergic neurons in the Arc differentially regulate feeding behaviors in response to hunger, satiety, and appetite, respectively. At the time of writing, the anatomical and electrophysiological characterization of these three neurons has not yet been intensively explored. Here, we interrogated the overall characterization of AgRP, POMC, and dopaminergic neurons using genetic mouse models, immunohistochemistry, and whole-cell patch recordings. We identified the distinct geographical location and intrinsic properties of each neuron in the Arc with the transgenic lines labelled with cell-specific reporter proteins. Moreover, AgRP, POMC, and dopaminergic neurons had different firing activities to ghrelin and leptin treatments. Ghrelin led to the increased firing rate of dopaminergic and AgRP neurons, and the decreased firing rate of POMC. In sharp contrast, leptin resulted in the decreased firing rate of AgRP neurons and the increased firing rate of POMC neurons, while it did not change the firing rate of dopaminergic neurons in Arc. These findings demonstrate the anatomical and physiological uniqueness of three hypothalamic Arc neurons to appetite control.
Highlights
The hypothalamus is a master unit that regulates energy homeostasis through the crosscorrelated operation of endocrine and sympathetic nervous systems
The hypothalamus consists of various nuclei that are mutually interconnected for efficient energy metabolisms, such as the ventromedial nucleus of the hypothalamus (VMH), the dorsomedial nucleus of the hypothalamus (DMH), lateral hypothalamus (LH), and arcuate nucleus (Arc)
We evaluated the volume of the cell body with high-resolution images and found the labelled size of tyrosine hydroxylase (TH), POMC, and Agouti-related protein (AgRP) in descending order (Figure 1C,D)
Summary
The hypothalamus is a master unit that regulates energy homeostasis through the crosscorrelated operation of endocrine and sympathetic nervous systems. The hypothalamus consists of various nuclei that are mutually interconnected for efficient energy metabolisms, such as the ventromedial nucleus of the hypothalamus (VMH), the dorsomedial nucleus of the hypothalamus (DMH), lateral hypothalamus (LH), and arcuate nucleus (Arc). The Arc dynamically regulates energy intake and expenditure via the on-demand integration of afferent inputs, such as circulating nutrients, hormones, and neurotransmitters [1,2]. The circuit activity of the hypothalamic Arc can be mainly executed by two distinct neuronal populations of satiety-triggering POMC neurons and hunger-promoting 4.0/). POMC and AgRP neurons have significantly increased the firing rate upon leptin and ghrelin treatment, respectively [5–7]
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