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. 2012 Dec 27:3:169.
doi: 10.3389/fendo.2012.00169. eCollection 2012.

Arcuate AgRP neurons and the regulation of energy balance

Céline Cansell  1 , Raphaël G P Denis, Aurélie Joly-Amado, Julien Castel, Serge Luquet
Affiliations

Arcuate AgRP neurons and the regulation of energy balance

Céline Cansell et al. Front Endocrinol (Lausanne). .

Abstract

The arcuate nucleus of the hypothalamus contains at least two populations of neurons that continuously monitor signals reflecting energy status and promote the appropriate behavioral and metabolic responses to changes in energy demand. Activation of neurons making pro-opiomelanocortin (POMC) decreases food intake and increases energy expenditure through activation of G protein-coupled melanocortin receptors via the release of α-melanocyte-stimulating hormone. Until recently, the prevailing idea was that the neighboring neurons [agouti-related protein (AgRP) neurons] co-expressing the orexigenic neuropeptides, AgRP, and neuropeptide Y increase feeding by opposing the anorexigenic actions of the POMC neurons. However, it has now been demonstrated that only AgRP neurons activation - not POMC neurons inhibition - is necessary and sufficient to promote feeding. Projections of AgRP-expressing axons innervate mesolimbic, midbrain, and pontine structures where they regulate feeding and feeding-independent functions such as reward or peripheral nutrient partitioning. AgRP neurons also make gamma aminobutyric acid , which is now thought to mediate many of critical functions of these neurons in a melanocortin-independent manner and on a timescale compatible with neuromodulation.

Keywords: GABA; agouti-related protein; dopamine; feeding behavior; metabolism; neuropeptide Y; obesity; reward.

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Figures

FIGURE 1
FIGURE 1
Sagittal (A) and coronal section (B) of a mouse brain showing in situ hybridization for mRNA encoding Agrp or Pomc and the connections recently described for AgRP neurons. Arcuate neurons project to the PVN, BNST, PBN, and VTA of the midbrain. The dopaminergic neurons of the VTA project to the nucleus accumbens (Nacc) to process the reward and motivational aspect of feeding. Gut-initiated viscerosensitive information and taste-related cues are routed to the NTS. The NTS targets the PBN and also receives serotoninergic input from the raphe obscurus (ROb) and the raphe magnus (RMg) and exerts an anorectic action through the glutamatergic excitation of the PBN. AgRP neurons integrate metabolic input of hunger and have direct connections to brain regions processing reward and motivation together with food-related cues such as palatability and aversive aspect. In situ hybridization picture were downloaded from the Allen Mouse Brain Atlas [http://mouse.brain-map.org/Seattle (WA): Allen Institute for Brain Science (Lein et al., 2007).© 2009].
FIGURE 2
FIGURE 2
Schematic representation of the feeding-neural circuitry. Arcuate AgRP neurons are located at the bottom of the third ventricle (3rd V) close to the circumventricular organs, the median eminence (ME). They exert a GABAergic tonic inhibition onto POMC-, OT-, CRH-, and TRH-expressing neurons from the PVN, the PBN and the dopaminergic neurons (DA) of the VTA. The PBN receives glutamatergic input from the NTS which is also a target for serotoninergic neurons of the raphe obscurus (ROb) and the raphe magnus (RMg). In the PVN, the synaptic properties of AgRP axons are such that GABA release could promote post-synaptic inhibition through the long after the propagation of action potential. The timescale of this electrical event is compatible with the neuromodulation of post-synaptic targets including the VTA, the PBN, and preganglionic structure of the PVN. Hence, hunger-activated neurons could have a role that extends beyond the acute regulation of feeding to autonomic control of nutrient partitioning, the modulation of gut-borne signals in the brainstem, and the fine tuning mesolimbic reward and motivational circuitry. (A/P) Antero-posterior stereotaxic coordinates are presented in mm from bregma below each section.
See this image and copyright information in PMC

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