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Olfactory and neuropeptide inputs to appetite neurons in the arcuate nucleus

ABSTRACT: We report RNA sequencing of single Agrp neurons isolated from the arcuate nucleus of the hypothalamus. Analyses of Agrp neuron transcriptomes reveals differential expression of receptors for multiple neuromodulators. Neuroanatomical mapping of known ligands of the receptors define subsets of neurons directly upstream of AgRP neurons in specific brain areas.

ORGANISM(S): Mus musculus

PROVIDER: GSE227909 | GEO | 2023/03/27

REPOSITORIES: GEO

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Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenaline

Project description:The arcuate nucleus of the hypothalamus (ARH) is one key structure controlling energy homeostasis. While it has been shown that the biogenic amines dopamine and serotonin modulate food intake controlling NPY/AgRP and/or POMC neurons in the ARH, the neural substrates that mediate the effect of noradrenaline (NA) on energy homeostasis remain elusive. By electrophysiological recordings and cell type-specific transcriptomics we show that the main neuronal populations in the ARH, NPY/AgRP and POMC neurons express a combination of excitatory and inhibitory adrenergic receptors (ARs). Surprisingly, NA had a clear differential effect on these neurons. Activation of NPY/AgRP neurons is mediated by _1A - and _- ARs, while POMC neurons are inhibited via _2A ARs. Collectively, our data indicate an orexigenic influence of NA on the ARH circuitry that controls energy balance

2017-10-26 | GSE106188 | GEO

Transcription Factors Dlx1 and Otp Segregate the Identity of Orexigenic/Anti-thermogenic- and Growth Promoting-Neurons in the Arcuate Nucleus

Project description:The hypothalamic arcuate nucleus contains multiple types of neurons controlling critical physiological processes. However, the gene regulatory network directing their development remains rudimentary. Here we report that two transcription factors Otp and Dlx1 segregate the identity of orexigenic/anti-thermogenic NPY/AgRP- and growth-promoting GHRH-neurons in the developing arcuate nucleus. Otp-null and Dlx1-null mice lose NPY/AgRP and GHRH expression, respectively. Dlx1-null mice also show enhanced expression of Otp/NPY/AgRP, which is normalized in Dlx1;Otp-double mutant mice. Correspondingly, Dlx1-null mice exhibit decreased growth, lower body temperature and increased feeding. Furthermore, our genome-wide studies identify Otp as a negative target gene of Dlx1. Therefore, Otp is critical for NPY/AgRP-neuronal development, while Dlx1 promotes GHRH-neuronal development and antagonizes NPY/AgRP-neuronal development. These results identify a mechanism for segregating the identity of two functionally related neurons, and the Dlx1-Otp axis likely contributes to coordinating energy balance and growth by maintaining a proper ratio of NPY/AgRP- to GHRH-neurons.

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Project description:Pro-opiomelanocortin (POMC)- and agouti-related peptide (AgRP)-expressing neurons of the arcuate nucleus of the hypothalamus (ARC) are oppositely regulated by caloric depletion and coordinately stimulate and inhibit homeostatic satiety, respectively. This bimodality is principally underscored by the antagonistic actions of these ligands at downstream melanocortin-4 receptors (MC4R) in the paraventricular nucleus of the hypothalamus (PVH). Although this population is critical to energy balance, the underlying neural circuitry remains unknown. Using mice expressing Cre recombinase in MC4R neurons, we demonstrate bidirectional control of feeding following real-time activation and inhibition of PVH(MC4R) neurons and further identify these cells as a functional exponent of ARC(AgRP) neuron-driven hunger. Moreover, we reveal this function to be mediated by a PVH(MC4R)→lateral parabrachial nucleus (LPBN) pathway. Activation of this circuit encodes positive valence, but only in calorically depleted mice. Thus, the satiating and appetitive nature of PVH(MC4R)→LPBN neurons supports the principles of drive reduction and highlights this circuit as a promising target for antiobesity drug development.

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2016-02-10 | E-GEOD-77766 | biostudies-arrayexpress

Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenaline

Project description:Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenaline

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Reciprocal activity of AgRP and POMC neurons governs coordinated control of feeding and metabolism

Project description:Agouti-related peptide (AgRP)- and proopiomelanocortin (POMC)-expressing neurons reciprocally regulate food intake. Here, we combined non-interacting recombinases to simultaneously express functionally opposing chemogenetic receptors in AgRP and POMC neurons allowing to compare metabolic responses in mice with simultaneous activation of AgRP and inhibition of POMC neurons with isolated activation of AgRP neurons or isolated inhibition of POMC neurons. These experiments revealed that food intake is regulated by the additive effect of AgRP-neuron activation and POMC-neuron inhibition, while systemic insulin sensitivity and gluconeogenesis are differentially modulated by isolated versus simultaneous regulation of AgRP and POMC neurons. We identified a neurocircuit engaging Npy1R-expressing neurons in the paraventricular nucleus of the hypothalamus (PVH), where activated AgRP- and inhibited POMC neurons synergize to promote food consumption and activate neurons in the nucleus tractus solitarii (NTS). We then performed single-nuclei RNA sequencing to define the molecular nature of Fos+ cells in the posterior NTS/AP area that respond to simultaneous chemogenetic intervention over AgRP and POMC neurons and identified TH+ neurons as candidates for receiving neuronal inputs initiated by the simultaneous and coordinated interplay between AgRP and POMC neurocircuits and relayed to the NTS area by the silenced glutamatergic Npy1R neurons.

2024-02-12 | GSE248391 | GEO

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