Regulation of feeding by somatostatin neurons in the tuberal nucleus

Luo, Sarah Xinwei; Huang, Ju; Qin, Li; Mohammad, Hasan; Lee, Chun‐Yao; Krishna, Kumar; Kok, Maun-Yeng Alison; Tan, Yu Lin; Lim, Joy; Li, Hongyu; Yeow, Ling Yun; Sun, Jingjing; He, Miao; Grandjean, Joanes; Sajikumar, Sreedharan; Han, Weiping; Fu, Yang Ming

doi:10.1126/science.aar4983

Cited by 88 publications

(111 citation statements)

References 35 publications

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“…Thus the uridine and uridine nucleotides may be novel regulators of body metabolism and function of AgRP/NPY neurons. In addition to AgRP/NpY neurons, ghrelin promotes activation of somatostatin neurons in the hypothalamic tuberal nucleus to promote feeding by inhibiting downstream neurons in the PVN and to the BNST (Luo et al 2018).…”

Section: Signaling In Agrp/npy Neuronsmentioning

confidence: 99%

The melanocortin pathway and control of appetite-progress and therapeutic implications

Baldini

Phelan

2019

Journal of Endocrinology

185

125

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The initial discovery thatob/obmice become obese because of a recessive mutation of the leptin gene has been crucial to discover the melanocortin pathway to control appetite. In the melanocortin pathway, the fed state is signaled by abundance of circulating hormones such as leptin and insulin, which bind to receptors expressed at the surface of pro-opiomelanocortin (POMC) neurons to promote processing of POMC to the mature hormone α-melanocyte-stimulating hormone (α-MSH). The α-MSH released by POMC neurons then signals to decrease energy intake by binding to melanocortin-4 receptor (MC4R) expressed by MC4R neurons to the paraventricular nucleus (PVN). Conversely, in the ‘starved state’ activity of agouti-related neuropeptide (AgRP) and of neuropeptide Y (NPY)-expressing neurons is increased by decreased levels of circulating leptin and insulin and by the orexigenic hormone ghrelin to promote food intake. This initial understanding of the melanocortin pathway has recently been implemented by the description of the complex neuronal circuit that controls the activity of POMC, AgRP/NPY and MC4R neurons and downstream signaling by these neurons. This review summarizes the progress done on the melanocortin pathway and describes how obesity alters this pathway to disrupt energy homeostasis. We also describe progress on how leptin and insulin receptors signal in POMC neurons, how MC4R signals and how altered expression and traffic of MC4R change the acute signaling and desensitization properties of the receptor. We also describe how the discovery of the melanocortin pathway has led to the use of melanocortin agonists to treat obesity derived from genetic disorders.

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Section: Signaling In Agrp/npy Neuronsmentioning

confidence: 99%

The melanocortin pathway and control of appetite-progress and therapeutic implications

Baldini

Phelan

2019

Journal of Endocrinology

185

125

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“…There may be other neuronostatin neurons in the central nervous system that we could not identify using this technique. A recent report showed that the somatostatin neurons localized in the tuberal nucleus regulated feeding [39], suggesting that these neurons could co-express neuronostatin. However, with immunohistochemistry, we, and others [2], could not detect neuronostatin immunoreactivity in the tuberal nucleus.…”

Section: Physiological Stimulation Of Neuronostatin Neurons and Invesmentioning

confidence: 99%

Glutamatergic Activation of Neuronostatin Neurons in the Periventricular Nucleus of the Hypothalamus

et al. 2020

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Neuronostatin, a newly identified anorexigenic peptide, is present in the central nervous system. We tested the hypothesis that neuronostatin neurons are activated by feeding as a peripheral factor and that the glutamatergic system has regulatory influences on neuronostatin neurons. The first set of experiments analyzed the activation of neuronostatin neurons by refeeding as a physiological stimulus and the effectiveness of the glutamatergic system on this physiological stimulation. The subjects were randomly divided into three groups: the fasting group, refeeding group, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)+refeeding group. We found that refeeding increased the phosphorylated signal transducers and transcription activator-5 (pSTAT5) expression in neuronostatin-positive neurons and that the CNQX injection significantly suppressed the number of pSTAT5-expressing neuronostatin neurons. The second set of experiments analyzed the activation pathways of neuronostatin neurons and the regulating effects of the glutamatergic system on neuronostatin neurons. The animals received intraperitoneal injections of glutamate receptor agonists (kainic acid, α-amino-3-hydroxy-5methyl-4-isoazepropionic acid (AMPA), and N-methyl-D-aspartate (NMDA)) or 0.9% NaCl. The number of c-Fos-expressing neuronostatin neurons significantly increased following the AMPA and NMDA injections. In conclusion, we found that the neuronostatin neurons were activated by peripheral or central signals, including food intake and/or glutamatergic innervation, and that the glutamate receptors played an important role in this activation.

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“…Collateralization could, in principle, impose temporal synchrony on targets of VMHvl Esr1 neurons and coordinate their activity. Given this collateralization, assigning specific functions to individual projections (e.g., by optogenetic terminal stimulation, (22,57) will be technically challenging, due to back-propagation and collateral redistribution of action potentials from optogenetically stimulated terminals.…”

Section: Vmhvl Esr1 Neurons Collateralize Broadly Yet Specificallymentioning

confidence: 99%

Connectional architecture of a mouse hypothalamic circuit node controlling social behavior

Kim²,

Yao

et al. 2018

Preprint

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Type 1 Estrogen receptor-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl Esr1 ) play a causal role in the control of social behaviors including aggression. Here we use six different viral-genetic tracing methods to map the connectional architecture of VMHvl Esr1 neurons. These data reveal a high level of input convergence and output divergence ("fan-in/fan-out") from and to over 30 distinct brain regions, with a high degree (~90%) of recurrence. Unlike GABAergic populations in other hypothalamic nuclei controlling feeding and parenting behavior, VMHvl Esr1 glutamatergic neurons collateralize to multiple targets. However, we identify two anatomically distinct subpopulations with anterior vs. posterior biases in their collateralization patterns. Surprisingly, these two subpopulations receive indistinguishable inputs. These studies suggest an overall system architecture in which an anatomically feed-forward sensory-to-motor processing stream is integrated with a dense, highly recurrent central processing circuit. This architecture differs from the "brain-inspired" feed-forward circuits used in certain types of artificial intelligence networks. 3 SIGNIFICANCEHow the cellular heterogeneity of brain nuclei maps onto circuit connectivity, the relationship of this anatomical mapping to behavioral function, and whether there are general principles underlying this relationship, remains poorly understood. Here we systematically map the connectivity of estrogen receptor-1-expressing neurons in the ventromedial hypothalamus (VMHvl Esr1 ), which control aggression and other social behaviors. We find that a relatively sparse, anatomically feed-forward sensory-to-motor processing stream is integrated with a dense, highly recurrent central processing circuit. Further, the VMHvl contains at least two subpopulations of Esr1 + neurons with different cell body characteristics and locations, with distinct patterns of collateralization to downstream targets. Nevertheless, these projectiondefined subpopulations receive similar inputs. This input-output organization appears distinct from those described in other hypothalamic nuclei.

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Regulation of feeding by somatostatin neurons in the tuberal nucleus

Cited by 88 publications

References 35 publications

The melanocortin pathway and control of appetite-progress and therapeutic implications

The melanocortin pathway and control of appetite-progress and therapeutic implications

Glutamatergic Activation of Neuronostatin Neurons in the Periventricular Nucleus of the Hypothalamus

Connectional architecture of a mouse hypothalamic circuit node controlling social behavior

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