Orexin-1 receptor immunoreactivity in chemically identified target neurons in the rat hypothalamus

Suzuki, Ryusuke; Shimojima, Hisa; Funahashi, Hiroomi; Nakajo, Shigeo; Yamada, Shuori; Guan, Jian-Lian; Tsurugano, Shinobu; Uehara, Kichiro; Takeyama, Yoichi; Kikuyama, Sakaé; Shioda, Seiji

doi:10.1016/s0304-3940(02)00140-4

Cited by 35 publications

(24 citation statements)

References 18 publications

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“…ARC POMC cells are surrounded by orexin-containing nerve terminals (Guan et al, 2001;Muroya et al, 2004), and there is strong orexin receptor-1 immunoreactivity in and around ARC POMC cells (Backberg et al, 2002;Suzuki et al, 2002). Microinjection of orexin into the ARC stimulates feeding (Muroya et al, 2004), and orexin reduces intracellular Ca 2ϩ levels in isolated POMC neurons (Muroya et al, 2004), suggesting that orexin may suppress the electrical activity of the anorexigenic POMC cells.…”

Section: Introductionmentioning

confidence: 99%

Electrical Inhibition of Identified Anorexigenic POMC Neurons by Orexin/Hypocretin

Zubcevic²,

Ashcroft³

et al. 2007

J. Neurosci.

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Proopiomelanocortin (POMC) neurons of the hypothalamic arcuate nucleus (ARC) suppress appetite, and lack of POMC-derived peptides or electrical silencing of POMC neurons causes obesity. ARC POMC neurons are surrounded by nerve terminals containing the wakefulness-promoting peptides orexins/hypocretins, but whether orexin affects their electrical activity has not been tested directly. Here we identify living ARC POMC cells in mouse brain slices by targeted expression of green fluorescent protein. Using whole-cell patch-clamp recordings, we show that orexin suppresses the spontaneous action potential firing of these neurons. Orexin-induced inhibition involves membrane hyperpolarization, a decreased excitatory synaptic drive, and an increased frequency of GABAergic inputs. Our results suggest a reduction in the electrical activity of ARC POMC neurons, which is mediated by changes in presynaptic inputs, contributes to the appetite-enhancing action of orexins.

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Section: Introductionmentioning

confidence: 99%

Electrical Inhibition of Identified Anorexigenic POMC Neurons by Orexin/Hypocretin

Zubcevic²,

Ashcroft³

et al. 2007

J. Neurosci.

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“…infusion of OX induces Fos-expression in NPY-containing neurons of the ARC, suggesting that OX-stimulated feeding occurs partly via NPY-mediated pathways [91]. The double immunostaining method has revealed that OX-1R [79] as well as leptin receptor [33] are co-localized with NPY-and POMC-containing neurons in the ARC. Triple immunolabeling reveals that some populations of NPY-and POMC-containing neurons in the ARC express both leptin and OX-1R (Fig.…”

Section: Newly Identified Gpcr Ligands Involved In Feeding Regulamentioning

confidence: 99%

“…OX-2R mRNA is mainly expressed in the cerebral cortex, nucleus accumbens, subthalamic nucleus, paraventricular thalamic nuclei, tuberomammilary nucleus and anterior pretectal nucleus [55,86]. Mutations in the OX-2R gene have been found in genetically narcoleptic dogs, while mice with targeted deletion of the prepro-orexin gene display a phenotype that is strikingly similar to human narcolepsy, suggesting that the interaction of OX with OX-2R has pivotal roles in the regulation of vigilance states [79]. On the other hand, treatment with an OX-1R antagonist has been shown to reduce food intake [34].…”

Section: Newly Identified Gpcr Ligands Involved In Feeding Regulamentioning

confidence: 99%

“…It may be interpreted that the OX-2R receptor is involved in regulating sleep state stability [59,92] and that OX-A acts on feeding regulation through its specific receptor OX-1R. Recently, the precise distribution of OX-1R in rat brain, based on immunohistochemical studies, was reported [35,79]. Western blot analysis of membranes from rat brain tissue showed that the antiserum used in a study from this laboratory [79] recognized a major polypeptide of 50 kDa size, the expected molecular mass of OX-1R given the amino acid sequence of OX-1R in brain [79].…”

Section: Newly Identified Gpcr Ligands Involved In Feeding Regulamentioning

confidence: 99%

“…Recently, the precise distribution of OX-1R in rat brain, based on immunohistochemical studies, was reported [35,79]. Western blot analysis of membranes from rat brain tissue showed that the antiserum used in a study from this laboratory [79] recognized a major polypeptide of 50 kDa size, the expected molecular mass of OX-1R given the amino acid sequence of OX-1R in brain [79]. We found that the most intense immunohistochemical staining for OX-1R occurred in the hypothalamus [81].…”

Section: Newly Identified Gpcr Ligands Involved In Feeding Regulamentioning

confidence: 99%

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Distribution and Neuronal Networks of Novel GPCR Ligands in Feeding Regulation

Takenoya

Kageyama

Guan

et al. 2005

Acta Histochem. Cytochem

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Recent studies have shown that a number of novel G-protein coupled receptor (GPCR) ligands localize in brain tissue and perform a range of physiological functions, some of which have been studied and clarified, and others about which less is known. Here, we wish to describe the distribution and localization of GPCR ligands identified thus far and to examine their involvement in neuronal networks, particularly those networks related to feeding regulation. The review analyzes published reports of morphological and physiological data looking mainly at the functional significance of feeding-regulation factors, such as those described by our research group and others, and neuronal interactions among these GPCR ligands in the hypothalamus. Cross-talk among several GPCR ligand-containing neuron types in the hypothalamus plays a role in determining feeding states. We introduce structural and functional characteristics of novel GPCR ligands and summarize the known interactions between several GPCR ligand-containing neuron types and leptin-targeting neurons in the hypothalamus. Finally, we present a new scheme summarizing neuronal networks with regard to feeding regulation in the hypothalamus. Research in this area will play an important role in clarifying neurologically-based causes for appetite dysfunction and establishing therapies for people suffering from such conditions.

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Organization of hypocretin/orexin efferents to locus coeruleus and basal forebrain arousal‐related structures

España

Reis

Valentino

et al. 2004

J of Comparative Neurology

135

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Hypocretin/orexin neurons give rise to an extensive projection system, portions of which innervate multiple regions associated with the regulation of behavioral state. These regions include the locus coeruleus, medial septal area, medial preoptic area, and substantia innominata. Evidence indicates that hypocretin modulates behavioral state via actions within each of these terminal fields. To understand better the circuitry underlying hypocretin-dependent modulation of behavioral state, the present study characterized the degree to which there exists: 1) lateralization of hypocretin efferents to basal forebrain and brainstem arousal-related regions, 2) topographic organization of basal forebrain- and brainstem-projecting hypocretin neurons, and 3) collateralization of individual hypocretin neurons to these arousal-related terminal fields. These studies utilized combined immunohistochemical identification of hypocretin neurons with single or double retrograde tracing from the locus coeruleus, medial preoptic area, medial septal area, and substantia innominata. Results indicate that approximately 80% of hypocretin efferents to basal forebrain regions project ipsilaterally, whereas projections to the locus coeruleus are more bilateral (65%). There was a slight preference for basal forebrain-projecting hypocretin neurons to be distributed within the medial half of the hypocretin cell group. In contrast, hypocretin neurons projecting to the locus coeruleus were located primarily within the dorsal half of the hypocretin cell group. Finally, a large proportion of hypocretin neurons appear to project simultaneously to at least two of the examined terminal fields. These latter observations suggest coordinated actions of hypocretin across multiple arousal-related regions.

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Orexin-1 receptor immunoreactivity in chemically identified target neurons in the rat hypothalamus

Cited by 35 publications

References 18 publications

Electrical Inhibition of Identified Anorexigenic POMC Neurons by Orexin/Hypocretin

Electrical Inhibition of Identified Anorexigenic POMC Neurons by Orexin/Hypocretin

Distribution and Neuronal Networks of Novel GPCR Ligands in Feeding Regulation

Organization of hypocretin/orexin efferents to locus coeruleus and basal forebrain arousal‐related structures

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