title: Transgenic approach reveals expression of the VPAC2 receptor in phenotypically defined neurons in the mouse suprachiasmatic nucleus and in its efferent target sites.
abstract: Circadian rhythms in mammals depend on the properties of cells in the suprachiasmatic nucleus (SCN). The retino-recipient core of the mouse SCN is characterized by vasoactive intestinal peptide (VIP) neurons. Expression within the SCN of VPAC2, a VIP receptor, is required for circadian rhythmicity. Using transgenic mice with beta-galactosidase as a marker for VPAC2, we have phenotyped VPAC2-expressing cells within the SCN and investigated expression of the VPAC2 marker at sites previously shown to receive VIP-containing SCN efferents. In situ hybridization and immunohistochemistry demonstrated identical distributions for VPAC2 mRNA and beta-galactosidase and coexpression of the two signals in the SCN. Double-label confocal immunofluorescence identified beta-galactosidase in 32% of the VIP and 31% of the calretinin neurons in the SCN core. Of the arginine-vasopressin neurons that characterize the SCN shell, 45% expressed beta-galactosidase. In contrast, this marker was not apparent in astrocytes within the SCN core or shell. Cell bodies containing beta-galactosidase were detected at sites reportedly receiving VIP-containing SCN efferents, including the subparaventricular zone and lateral septum and the anteroventral periventricular, preoptic suprachiasmatic, medial preoptic and paraventricular hypothalamic nuclei. The detection of a marker for VPAC2 expression in the SCN in almost one-third of the VIP and calretinin core neurons and nearly half of the arginine-vasopressin shell neurons and also in cell bodies at sites receiving VIP-immunoreactive projections from the SCN indicates that VPAC2 may contribute to autoregulation and/or coupling within the SCN core and to the control of the SCN shell and sites distal to this nucleus.
authors.affiliation: Centre for Neuroscience Research, King's College London SE1 1UL, UK.
authors.forename: Imre
authors.initials: I
authors.lastname: Kalló
authors.forename: Theodosis
authors.initials: T
authors.lastname: Kalamatianos
authors.forename: Nzinga
authors.initials: N
authors.lastname: Wiltshire
authors.forename: Sanbing
authors.initials: S
authors.lastname: Shen
authors.forename: W John
authors.initials: WJ
authors.lastname: Sheward
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Harmar
authors.forename: Clive W
authors.initials: CW
authors.lastname: Coen
mesh_terms: D000818:Animals; D004525:Efferent Pathways / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D010641:Phenotype; D018005:Receptors, Vasoactive Intestinal Peptide / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D013493:Suprachiasmatic Nucleus / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II