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Hypothalamic Suprachiasmatic Nuclei (hypothalamic + suprachiasmatic_nucleus)
Selected AbstractsA hVIPR transgene as a novel tool for the analysis of circadian function in the mouse suprachiasmatic nucleusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2003V. M. King Abstract A mouse bearing a novel transgene encoding the human VPAC2 receptor (hVIPR; Shen et al. (2000) PNAS, 97, 11575,11580) was used to investigate circadian function in the hypothalamic suprachiasmatic nuclei (SCN). Neurons expressing hVPAC2R, detected by a beta-galactosidase (,-GAL) tag, have a distinct distribution within the SCN, closely matching that of neurophysin (NP) neurons and extending into the region of peptide histidine isoleucine (PHI) cells. In common with NP and PHI cells, neurons expressing hVPAC2R are circadian in nature, as revealed by synchronous rhythmic expression of mPERIOD (mPER) proteins. A population of SCN cells not expressing PHI, NP or hVPAC2R exhibited circadian PER expression antiphasic with the rest of the SCN. Nocturnal light exposure induced mPER1 in the ventral SCN and mPER2 widely across the nucleus. Induction of nuclear mPER2 in hVPAC2R cells confirmed their photic responsiveness. Having established their circadian properties, we tested the utility of SCN neurons expressing the hVIPR transgene as functionally and anatomically explicit markers for SCN tissue grafts. Prenatal SCN tissue from hVIPR transgenic pups survived transplantation into adult CD1 mice, and expressed ,-GAL, PER and PHI. Over a series of studies, hVIPR transgenic SCN grafts restored circadian activity rhythms to 17 of 72 arrhythmic SCN lesioned recipients (23.6%). By using heterozygous hVIPR transgenic grafts on a heterozygous Clock mutant background we confirmed that restored activity rhythms were conferred by the donor tissue. We conclude that the hVIPR transgene is a powerful and flexible tool for examination of circadian function in the mouse SCN. [source] The mouse VPAC2 receptor confers suprachiasmatic nuclei cellular rhythmicity and responsiveness to vasoactive intestinal polypeptide in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2003David J. Cutler Abstract Expression of coherent and rhythmic circadian (, 24 h) variation of behaviour, metabolism and other physiological processes in mammals is governed by a dominant biological clock located in the hypothalamic suprachiasmatic nuclei (SCN). Photic entrainment of the SCN circadian clock is mediated, in part, by vasoactive intestinal polypeptide (VIP) acting through the VPAC2 receptor. Here we used mice lacking the VPAC2 receptor (Vipr2,/,) to examine the contribution of this receptor to the electrophysiological actions of VIP on SCN neurons, and to the generation of SCN electrical firing rate rhythms SCN in vitro. Compared with wild-type controls, fewer SCN cells from Vipr2,/, mice responded to VIP and the VPAC2 receptor-selective agonist Ro 25-1553. By contrast, similar proportions of Vipr2,/, and wild-type SCN cells responded to gastrin-releasing peptide, arginine vasopressin or N -methyl- d -aspartate. Moreover, VIP-evoked responses from control SCN neurons were attenuated by the selective VPAC2 receptor antagonist PG 99-465. In firing rate rhythm experiments, the midday peak in activity observed in control SCN cells was lost in Vipr2,/, mice. The loss of electrical activity rhythm in Vipr2,/, mice was mimicked in control SCN slices by chronic treatment with PG 99-465. These results demonstrate that the VPAC2 receptor is necessary for the major part of the electrophysiological actions of VIP on SCN cells in vitro, and is of fundamental importance for the rhythmic and coherent expression of circadian rhythms governed by the SCN clock. These findings suggest a novel role of VPAC2 receptor signalling, and of cell-to-cell communication in general, in the maintenance of core clock function in mammals, impacting on the cellular physiology of SCN neurons. [source] Spatial and temporal variation of passer Per2 gene expression in two distinct cell groups of the suprachiasmatic hypothalamus in the house sparrow (Passer domesticus)EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2002Ute Abraham Abstract In mammals, the major pacemaker controlling circadian rhythmicity is located in the hypothalamic suprachiasmatic nuclei. Although there is evidence for the presence of a hypothalamic circadian oscillator in birds from lesioning studies, neuroanatomical, neurochemical and functional investigations have failed to identify its exact location. Two cell groups in the avian hypothalamus have been shown to bear characteristics of the mammalian suprachiasmatic nucleus: the suprachiasmatic nucleus and the lateral hypothalamic retinorecipient nucleus. We cloned an avian period homologue (pPer2) and investigated the temporal and spatial expression pattern of this gene in the house sparrow hypothalamus using in situ hybridization. Applying quantitative morphometry, we found rhythmic expression of pPer2 during light,dark as well as in constant conditions in the suprachiasmatic nucleus and in the lateral hypothalamus. The temporal and spatial distribution of pPer2 expression in the suprachiasmatic nucleus suggest a longitudinal compartmentalization of the nucleus with period gene expression being initiated in the most rostral portion of the suprachiasmatic nucleus before lights on. In the lateral hypothalamus, phasing of pPer2 -rhythmicity appeared different from the suprachiasmatic nucleus. The major difference between light,dark and constant conditions was a decrease in the amplitude of pPer2 rhythmicity in the suprachiasmatic nucleus. Our data demonstrate that, unlike in mammals, Per gene expression in the suprachiasmatic hypothalamus of the house sparrow is not confined to a single cell group, indicating a more complex organization of the circadian oscillator in the hypothalamus of birds. [source] Opposing actions of neuropeptide Y and light on the expression of circadian clock genes in the mouse suprachiasmatic nucleiEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2002Elizabeth S. Maywood Abstract The circadian clockwork of the hypothalamic suprachiasmatic nuclei (SCN) is synchronized by light and by nonphotic cues. The core timing mechanism is cell-autonomous, based on an autoregulatory transcriptional/translational feedback loop of circadian genes and their products. This study investigated the effects of neuropeptide Y (NPY), a potent nonphotic resetting cue, and its interaction with light in regulating clock gene expression in the SCN in vivo. Injection of NPY adjacent to the SCN and transfer to darkness 7 h before scheduled lights out, shifted the circadian activity,rest cycle. Exposure to light for 1 h immediately after NPY infusion blocked this behavioural response. NPY-induced shifts were accompanied by suppression of both mPer1 and mPer2 mRNA in the SCN, assessed 3 h after infusion. mPer mRNAs were not altered 1 h after infusion. Levels of mClock mRNA or mCLOCK immunoreactivity in the SCN were not affected by NPY at either time point. In parallel to the behavioural response, the NPY-induced suppression of mPer genes in the SCN was attenuated when a light pulse was delivered immediately after the infusion. These results identify mPer1 and mPer2 as molecular targets for both photic and nonphotic (NPY-induced) resetting of the clockwork, and support a synthetic model of circadian entrainment based upon convergent up- and downregulation of mPer expression. [source] Food-reward signalling in the suprachiasmatic clockJOURNAL OF NEUROCHEMISTRY, Issue 6 2010Jorge Mendoza J. Neurochem. (2010) 112, 1489,1499. Abstract Under special restricted feeding conditions the mammalian circadian clock, contained in the hypothalamic suprachiasmatic nucleus (SCN), can be entrained by food. During food restriction, hungry animals are very motivated to obtain food. This motivational state could be a key component in altering the SCN timing by feeding. In order to comprehend how hedonic signals of food affect the SCN clock, we evaluated the effects of a daily palatable snack on the behavioural rhythm of mice fed ad libitum with regular food, and housed under constant darkness conditions. As light synchronization of the SCN is modulated by feeding/metabolic cues, the effects of a palatable meal coupled to a light pulse were tested on behavioural and molecular rhythms. A daily palatable snack entrained behavioural rhythms of mice in constant darkness conditions. Furthermore, palatable meal access at the activity onset reduced light-induced behavioural phase-delays and Period genes expression in the SCN. In addition, an increase in the dopamine content and Period genes expression in the forebrain of mice was observed, concomitant with a c- FOS activation in dopaminergic and orexinergic neurons, suggesting that the effects of a palatable snack on the SCN clock are mediated by the reward/arousal central systems. In conclusion, this study establishes an underlying sensitivity of the master circadian clock to changes in motivational states related to palatable food intake. [source] Light induces Fos expression via extracellular signal-regulated kinases 1/2 in melanopsin-expressing PC12 cellsJOURNAL OF NEUROCHEMISTRY, Issue 3 2010Marie-Louise Moldrup J. Neurochem. (2010) 112, 797,806. Abstract The photopigment melanopsin is expressed in a subtype of mammalian ganglion cells in the retina that project to the circadian clock in the hypothalamic suprachiasmatic nucleus to mediate non-visual light information. Melanopsin renders these retinal ganglion cells intrinsically photosensitive and the cells respond to light by a membrane depolarization and induction of the immediate early response gene Fos. Previous studies showed that the light activated melanopsin-induced signaling, the phototransduction, leading to depolarization of the membrane resembles the invertebrate opsins, which involves a G,q/11 coupled phospholipase C activation. However, the signaling proteins mediating melanopsin-induced Fos expression are unresolved. In this study, we examined the phototransduction leading to Fos expression in melanopsin-transfected PC12 cells. A pivotal role of the extracellular signal-regulated protein kinase 1/2 (ERK1/2) was found as pharmacological blockage of this kinase suppressed the light-induced Fos expression. Illumination increased the inositol phosphate turnover and induced phosphorylation of ERK1/2 and p38 but not the c-Jun N-terminal kinase. The G,q/11 protein inhibitor YM254890 attenuated these intracellular light responses. Our data strongly indicate that G,q/11 -mediated ERK1/2 activation is essential for expression of Fos upon illumination of melanopsin-expressing PC12 cells. [source] Daily Rhythms in Glucose Metabolism: Suprachiasmatic Nucleus Output to Peripheral TissueJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2003S. E. La Fleur Abstract The body has developed several control mechanisms to maintain plasma glucose concentrations within strict boundaries. Within those physiological boundaries, a clear daily rhythm in plasma glucose concentrations is present; this rhythm depends on the biological clock, which is located in the hypothalamic suprachiasmatic nucleus (SCN), and is independent of the daily rhythm in food intake. Interestingly, there is also a daily rhythm in glucose uptake, which also depends on the SCN and follows the same pattern as the daily rhythm in plasma glucose concentrations; both rise before the onset of activity. Thus, the SCN prepares the individual for the upcoming activity period in two different ways: by increasing plasma glucose concentrations and by facilitating tissue glucose uptake. In addition to this anticipation of glucose metabolism to expected glucose demands, the SCN also influences, depending on the time of the day, the responses of pancreas and liver to abrupt glucose changes (such as a glucose rise after a meal or hypoglycaemia). This review presents the view that the SCN uses different routes to (i) maintain daily glucose balance and (ii) set the level of the endocrine response to abrupt blood glucose changes. [source] | ||||||||||