Expression of<i>Period</i>Genes: Rhythmic and Nonrhythmic Compartments of the Suprachiasmatic Nucleus Pacemaker

Hamada, Toshiyuki; LeSauter, Joseph; Venuti, Judith M.; Silver, Rae

doi:10.1523/jneurosci.21-19-07742.2001

Cited by 215 publications

(259 citation statements)

References 69 publications

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“…These SCN regions are structurally and functionally heterogeneous based on different neuropeptide expression, photic input and sensitivity to light, expression pattern of clock and clock-driven genes and cytological features in general [11,34,15]. Distinct roles for these two regions in the regulation of circadian rhythms have been proposed [30,5].…”

Section: Discussionmentioning

confidence: 99%

Development of the mouse suprachiasmatic nucleus: Determination of time of cell origin and spatial arrangements within the nucleus

Kabrita

Davis

2008

Brain Research

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The suprachiasmatic nucleus (SCN) in mammals functions as the principal circadian pacemaker synchronizing diverse physiological and behavioral processes to environmental stimuli. It consists of heterogeneous populations of cells with unique spatial organization that can vary among species, but are commonly discussed within a framework of two principal regions, the ventrolateral or dorsomedial halves of the nucleus or in other instances the core and shell. In both hamsters and rats, cells of different SCN regions have been shown to have different developmental histories. Using bromodeoxyuridine as a marker of cell division, the present study investigated the time of SCN cell origin in mice (C57BL/6) and their settling patterns within the nucleus. Results show that SCN cytogenesis occurs between embryonic days 12 and 15 and is complete 5 days prior to birth. Cells born on embryonic day 12 are mainly confined to a ventrolateral region of the mid-SCN, whereas cells produced later on embryonic days 13.5 and 14.5 form a cap around the cells produced first and extend into the posterior and anterior ends of the nucleus. These results suggest an ordered spatiotemporal program of SCN cytogenesis whereby a mid-SCN core is born first followed by a surrounding shell of later-born cells. Variation in cytogenesis could affect the relative sizes of different SCN regions and, thereby, affect its function. The relative contributions of a highly ordered program of cytogenesis and intercellular interactions after post-mitotic cells leave the germinal epithelium remain to be determined.

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Section: Discussionmentioning

confidence: 99%

Development of the mouse suprachiasmatic nucleus: Determination of time of cell origin and spatial arrangements within the nucleus

Kabrita

Davis

2008

Brain Research

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“…Use of immediateearly genes and clock genes as markers indicates that there are two fundamentally different responses of SCN neurons and that these are well aligned with "core" and "shell" compartments. In constant darkness (DD), rhythmic oscillation of Per1 and Per2 expression occurs in the shell (mouse, Shigeyoshi et al 1997;rat, Yan et al 1999;hamster, Hamada et al 2001), but depending on the methods used, such oscillation is very low or not detectable in the core (hamster, Hamada et al 2001;mouse, Karatsoreos et al 2004). On the other hand, light-induced Per1 and Per2 expression is largely limited to the core SCN.…”

Section: Function Of Scn Subregionsmentioning

confidence: 99%

Exploring Spatiotemporal Organization of SCN Circuits

Yan

Karatsoreos

LeSauter

et al. 2007

Cold Spring Harbor Symposia on Quantitative Biology

104

111

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Suprachiasmatic nucleus (SCN) neuroanatomy has been a subject of intense interest since the discovery of the SCN's function as a brain clock and subsequent studies revealing substantial heterogeneity of its component neurons. Understanding the network organization of the SCN has become increasingly relevant in the context of studies showing that its functional circuitry, evident in the spatial and temporal expression of clock genes, can be reorganized by inputs from the internal and external environment. Although multiple mechanisms have been proposed for coupling among SCN neurons, relatively little is known of the precise pattern of SCN circuitry. To explore SCN networks, we examine responses of the SCN to various photic conditions, using in vivo and in vitro studies with associated mathematical modeling to study spatiotemporal changes in SCN activity. We find an orderly and reproducible spatiotemporal pattern of oscillatory gene expression in the SCN, which requires the presence of the ventrolateral core region. Without the SCN core region, behavioral rhythmicity is abolished in vivo, whereas low-amplitude rhythmicity can be detected in SCN slices in vitro, but with loss of normal topographic organization. These studies reveal SCN circuit properties required to signal daily time.

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“…Most (79%) of the CalB cells within the CalB subnucleus express Fos in response to a light pulse (Silver et al, 1996). Per1 and Per2 mRNA are induced by light in the CalB subregion (Hamada et al, 2001). Finally, the CalB subregion seems necessary for the maintenance of circadian rhythms of locomotor activity ).…”

Section: Connections Of Calb-immunoreactive Cells Within the Scnmentioning

confidence: 99%

“…This indicates that the CalB subregion is essential for the maintenance of locomotor rhythmicity. Examination of clock gene expression indicates that there is no detectable rhythm of Per1 and Per2 mRNA in the CalB subregion, although high amplitude rhythmic expression is seen in other parts of the SCN (Hamada et al, 2001). Importantly, light induces Per1 and Per2 in the CalB subnucleus at night, but not during the day.…”

mentioning

confidence: 96%

Calbindin-D28K cells selectively contact intra-SCN neurons

et al. 2002

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Calbindin-D 28K -immunoreactive cells are tightly packed within a discrete region of the caudal aspect of the suprachiasmatic nuclei of hamsters. These cells receive direct retinal input and are Fos-positive in response to a light pulse. Knowledge of their afferent and efferent connections is necessary to understand suprachiasmatic nucleus organization. The first aim of the present study is to identify interconnections between calbindin and other peptidergic cells of the suprachiasmatic nuclei, using epi-and confocal microscopy and intra-suprachiasmatic nucleus tract tracing. The results indicate that essentially all calbindin cells receive numerous appositions from vasoactive intestinal polypeptide (VIP), neuropeptide Y and serotonin fibers and that most receive appositions from gastrin releasing peptide (GRP) and cholecystokinin (CCK) fibers. Reciprocal connections are seen from VIP, GRP and CCK cells but surprisingly, not from dorsomedial vasopressin cells. Injection of biotinylated dextran amine into the suprachiasmatic nucleus indicates that the ventrolateral suprachiasmatic nucleus projects to the entire nucleus, while the dorsal and medial regions of the suprachiasmatic nucleus project densely to most of the nucleus, except to the calbindin region. Analysis of colocalization of the peptides in the calbindin cell region shows that 91% of the substance P cells, 42% of the GRP cells and 60% of the VIP cells in the calbindin subnucleus coexpress calbindin-D 28K .Our results reveal a highly specialized topographical organization of connections among suprachiasmatic nucleus cells. Keywords suprachiasmatic nucleus; calbindin; vasopressin; confocal microscopy; tract tracingThe suprachiasmatic nuclei (SCN) are the locus of the brain clock regulating circadian rhythms in mammals (reviewed in Silver and Moore, 1998). In rodents, these paired hypothalamic nuclei are each composed of about 8000 neurons that are heterogeneous in their content of neuronal antigens (van den Pol, 1980;van den Pol and Tsujimoto, 1985). Some of the neuropeptides that have been identified to date in the rodent SCN are vasopressin (AVP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine, gastrin releasing peptide (GRP), sub-stance P (SP), cholecystokinin (CCK) and somatostatin. We have reported that a subregion in the caudal SCN is characterized by the (Silver et al., 1996). These cells are densely packed, receive direct retinal synaptic input (Bryant et al., 2000) and are responsive to photic stimuli, with about 80% of the cells showing Fos-like immunoreactivity (ir) following a light pulse given during subjective night (Silver et al., 1996). The foregoing evidence indicates these CalB cells are on the input pathway for photic stimuli reaching the SCN.The function of this subregion of the SCN has been examined in hamsters. Animals with lesions that destroyed the CalB subnucleus, but spared other compartments of the SCN, lost their locomotor activity rhythm. Animals with partial bilateral SCN lesions sparing part ...

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Expression ofPeriodGenes: Rhythmic and Nonrhythmic Compartments of the Suprachiasmatic Nucleus Pacemaker

Cited by 215 publications

References 69 publications

Development of the mouse suprachiasmatic nucleus: Determination of time of cell origin and spatial arrangements within the nucleus

Development of the mouse suprachiasmatic nucleus: Determination of time of cell origin and spatial arrangements within the nucleus

Exploring Spatiotemporal Organization of SCN Circuits

Calbindin-D28K cells selectively contact intra-SCN neurons

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