Expression of VIP and/or PACAP receptor mRNA in peptide synthesizing cells within the suprachiasmatic nucleus of the rat and in its efferent target sites

The suprachiasmatic nucleus (SCN) contains the predominant circadian pacemaker in mammals. Considerable evidence indicates that VPAC2 and PAC1, receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase‐activating peptide (PACAP), play critical roles in maintaining and entraining circadian rhythms. Retinal projections to the rat SCN contain PACAP and terminate mostly in the ventral SCN, the site of VIP neurons. The incidence of VPAC2 and PAC1 mRNAs within distinct neuronal populations of the rat SCN has been determined using double‐label in situ hybridization. VPAC2 mRNA was detected in almost all arginine‐vasopressin (AVP) neurons of the dorsomedial SCN and in 41% of the VIP neurons; somatostatin (SST) neurons, predominantly in dorsomedial and intermediate regions, showed a decreased incidence (23%). PAC1 mRNA was present in nearly half of the VIP and SST neurons (45% and 40%, respectively) and in one‐third of the AVP neurons (32%). Cells expressing VPAC2 mRNA also were detected in diencephalic areas that receive VIP‐immunoreactive SCN efferents, such as the peri‐suprachiasmatic region, lateral subparaventricular zone, parvocellular hypothalamic paraventricular subdivisions, dorsomedial hypothalamic nucleus, and anterior thalamic paraventricular and paratenial nuclei. The extensive distribution of PAC1 mRNA within the SCN suggests that actions of PACAP are not restricted to the predominantly retinorecipient region. The presence of VPAC2 mRNA in nearly half the VIP neurons, in almost all the AVP neurons, and at sites receiving VIP‐immunoreactive SCN efferents suggests that the SCN VIP neurons are coupled and/or autoregulated and also influence the AVP‐containing dorsomedial SCN and distal sites via VPAC2. J. Comp. Neurol. 475:19–35, 2004. © 2004 Wiley‐Liss, Inc.

[1]  K. Shinohara,et al.  Endogenous circadian rhythmicity of somatostatin like-immunoreactivity in the rat suprachiasmatic nucleus , 1993, Brain Research.

[2]  J. Hannibal,et al.  Neurotransmitters of the retino-hypothalamic tract , 2002, Cell and Tissue Research.

[3]  Laurent Journot,et al.  Differential signal transduction by five splice variants of the PACAP receptor , 1993, Nature.

[4]  E. Maywood,et al.  A hVIPR transgene as a novel tool for the analysis of circadian function in the mouse suprachiasmatic nucleus , 2003, The European journal of neuroscience.

[5]  V. Grinevich,et al.  Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on gonadotropin-releasing hormone and somatostatin gene expression in the rat brain. , 1996, Brain research. Molecular brain research.

[6]  H. Karten,et al.  Immunocytochemical localization of vasoactive intestinal polypeptide- containing cells and processes in the suprachiasmatic nucleus of the rat: light and electron microscopic analysis , 1981, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[7]  L. Sander,et al.  Involvement of vasopressin and corticotropin-releasing hormone in VIP- and PHI-induced secretion of ACTH and corticosterone , 1995, Neuropeptides.

[8]  H. Romijn,et al.  Anatomical and functional demonstration of a multisynaptic suprachiasmatic nucleus adrenal (cortex) pathway , 1999, The European journal of neuroscience.

[9]  L W Swanson,et al.  Efferent projections of the suprachiasmatic nucleus: II. Studies using retrograde transport of fluorescent dyes and simultaneous peptide immunohistochemistry in the rat , 1987, The Journal of comparative neurology.

[10]  K. Obrietan,et al.  PACAP potentiates L-type calcium channel conductance in suprachiasmatic nucleus neurons by activating the MAPK pathway. , 2002, Journal of neurophysiology.

[11]  Jun Lu,et al.  Critical Role of Dorsomedial Hypothalamic Nucleus in a Wide Range of Behavioral Circadian Rhythms , 2003, The Journal of Neuroscience.

[12]  S. Hisano,et al.  Neuronal associations in the rat suprachiasmatic nucleus demonstrated by immunoelectron microscopy , 1992, The Journal of comparative neurology.

[13]  H. Okamura,et al.  Vasoactive intestinal peptide immunoreactive neurons in the rat suprachiasmatic nucleus demonstrate diurnal variation , 1989, Brain Research.

[14]  J. Hannibal,et al.  Serotonin inhibits glutamate‐ but not PACAP‐induced per gene expression in the rat suprachiasmatic nucleus at night , 2003, The European journal of neuroscience.

[15]  J. Vanecek,et al.  In vitro entrainment of the circadian rhythm of vasopressin-releasing cells in suprachiasmatic nucleus by vasoactive intestinal polypeptide , 2000, Brain Research.

[16]  G. E. Pickard,et al.  Vasoactive Intestinal Peptide Efferent Projections of the Suprachiasmatic Nucleus in Anterior Hypothalamic Transplants: Correlation with Functional Restoration of Circadian Behavior , 1995, Experimental Neurology.

[17]  Paolo Sassone-Corsi,et al.  A Web of Circadian Pacemakers , 2002, Cell.

[18]  C. Colwell,et al.  Regulation of inhibitory synaptic transmission by vasoactive intestinal peptide (VIP) in the mouse suprachiasmatic nucleus. , 2003, Journal of neurophysiology.

[19]  H. Gainer,et al.  Neuronal activity is required for the circadian rhythm of vasopressin gene transcription in the suprachiasmatic nucleus in vitro. , 2002, Endocrinology.

[20]  E. Maywood,et al.  The VPAC2 Receptor Is Essential for Circadian Function in the Mouse Suprachiasmatic Nuclei , 2002, Cell.

[21]  E. Maywood,et al.  A hVIPR transgene as a novel tool for the analysis of circadian function in the mouse suprachiasmatic nucleus , 2003, The European journal of neuroscience.

[22]  M. Harrington,et al.  Pituitary Adenylate Cyclase Activating Peptide Phase Shifts Circadian Rhythms in a Manner Similar to Light , 1999, The Journal of Neuroscience.

[23]  J. Hannibal,et al.  Pituitary adenylate cyclase-activating polypeptide induces period1 and period2 gene expression in the rat suprachiasmatic nucleus during late night , 2001, Neuroscience.

[24]  R. Moore,et al.  Paraventricular–subparaventricular hypothalamic lesions selectively affect circadian function , 2002, Chronobiology international.

[25]  H. Okamura,et al.  Gradients in the circadian expression of Per1 and Per2 genes in the rat suprachiasmatic nucleus , 2002, The European journal of neuroscience.

[26]  L. P. Morin,et al.  Morphological Correlates of Circadian Rhythm Restoration Induced by Transplantation of the Suprachiasmatic Nucleus in Hamsters , 1994, Experimental Neurology.

[27]  K. Shinohara,et al.  Temporal profiles of vasoactive intestinal polypeptide precursor mRNA and its receptor mRNA in the rat suprachiasmatic nucleus. , 1999, Brain research. Molecular brain research.

[28]  S. Reppert,et al.  Coordination of circadian timing in mammals , 2002, Nature.

[29]  C. Pennartz,et al.  Neurons of the rat suprachiasmatic nucleus show a circadian rhythm in membrane properties that is lost during prolonged whole-cell recording 1 Published on the World Wide Web on 20 October 1998. 1 , 1999, Brain Research.

[30]  J. Vanecek,et al.  Melatonin inhibits spontaneous and VIP-induced vasopressin release from suprachiasmatic neurons , 1998, Brain Research.

[31]  Mark J. Zylka,et al.  A Molecular Mechanism Regulating Rhythmic Output from the Suprachiasmatic Circadian Clock , 1999, Cell.

[32]  H. Romijn,et al.  Differences in colocalization between Fos and PHI, GRP, VIP and VP in neurons of the rat suprachiasmatic nucleus after a light stimulus during the phase delay versus the phase advance period of the night , 1996, The Journal of comparative neurology.

[33]  H. Groenewegen,et al.  Organization of the thalamostriatal projections in the rat, with special emphasis on the ventral striatum , 1990, The Journal of comparative neurology.

[34]  H. Korf,et al.  The pituitary adenylate cyclase-activating polypeptide-induced phosphorylation of the transcription factor CREB (cAMP response element binding protein) in the rat suprachiasmatic nucleus is inhibited by melatonin , 1997, Neuroscience Letters.

[35]  E. Maywood,et al.  Entrainment of the circadian system of mammals by nonphotic cues. , 1998, Chronobiology international.

[36]  B. Rusak,et al.  Neuropeptides phase shift the mammalian circadian pacemaker , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[37]  T. Nishiwaki,et al.  Emergence of VIP rhythmicity following somatostatin depletion in the rat suprachiasmatic nucleus , 1994, Brain Research.

[38]  A. Harmar,et al.  Circadian changes in the expression of vasoactive intestinal peptide 2 receptor mRNA in the rat suprachiasmatic nuclei. , 1998, Brain research. Molecular brain research.

[39]  C. Sylvester,et al.  Suprachiasmatic nucleus projection to the medial prefrontal cortex: a viral transneuronal tracing study , 2002, Neuroscience.

[40]  T. Yagi,et al.  Changes in circadian period and morphology of the hypothalamic suprachiasmatic nucleus in fyn kinase-deficient mice , 2000, Brain Research.

[41]  L. Eiden,et al.  Five Discrete Cis-active Domains Direct Cell Type-specific Transcription of the Vasoactive Intestinal Peptide (VIP) Gene* , 1998, The Journal of Biological Chemistry.

[42]  M. Markman,et al.  Projections of the suprachiasmatic nucleus to stress‐related areas in the rat hypothalamus: A light and electron microscopic study , 1993, The Journal of comparative neurology.

[43]  K. Chihara,et al.  Suprachiasmatic nucleus neurons immunoreactive for vasoactive intestinal polypeptide have synaptic contacts with axons immunoreactive for neuropeptide Y: An immunoelectron microscopic study in the rat , 1988, Neuroscience Letters.

[44]  Y Sakaki,et al.  Resetting central and peripheral circadian oscillators in transgenic rats. , 2000, Science.

[45]  Sumio Takahashi,et al.  Circadian changes in arginine vasopressin level in the suprachiasmatic nuclei in the rat , 1991, Neuroscience Letters.

[46]  R. Zoeller,et al.  The control of circadian rhythms and the levels of vasoactive intestinal peptide mRNA in the suprachiasmatic nucleus are altered in spontaneously hypertensive rats , 1994, Brain Research.

[47]  A. Kalsbeek,et al.  Output pathways of the mammalian suprachiasmatic nucleus: coding circadian time by transmitter selection and specific targeting , 2002, Cell and Tissue Research.

[48]  C. Weitz,et al.  Regulation of Daily Locomotor Activity and Sleep by Hypothalamic EGF Receptor Signaling , 2001, Science.

[49]  J. Bockaert,et al.  Alternative Splicing in the N-terminal Extracellular Domain of the Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Receptor Modulates Receptor Selectivity and Relative Potencies of PACAP-27 and PACAP-38 in Phospholipase C Activation* , 1996, The Journal of Biological Chemistry.

[50]  Rae Silver,et al.  Phase Resetting Light Pulses Induce Per1 and Persistent Spike Activity in a Subpopulation of Biological Clock Neurons , 2003, The Journal of Neuroscience.

[51]  M. Jouvet,et al.  VIP binding sites in adult rat hypothalamus: Nuclear distribution and daily variations , 1994, Peptides.

[52]  J. Hannibal,et al.  The Photopigment Melanopsin Is Exclusively Present in Pituitary Adenylate Cyclase-Activating Polypeptide-Containing Retinal Ganglion Cells of the Retinohypothalamic Tract , 2002, The Journal of Neuroscience.

[53]  K. Nagai,et al.  Changes in light-induced phase shift of circadian rhythm in mice lacking PACAP. , 2003, Biochemical and biophysical research communications.

[54]  P. Pévet,et al.  Per and neuropeptide expression in the rat suprachiasmatic nuclei: compartmentalization and differential cellular induction by light , 2002, Brain Research.

[55]  R. Moore,et al.  Efferent projections of the paraventricular thalamic nucleus in the rat , 1995, The Journal of comparative neurology.

[56]  R. Leak,et al.  Topographic organization of suprachiasmatic nucleus projection neurons , 2001, The Journal of comparative neurology.

[57]  H. Romijn,et al.  Evidence from Confocal Fluorescence Microscopy for a Dense, Reciprocal Innervation Between AVP‐,somatostatin‐, VIP/PHI‐, GRP‐ and VIP/PHI/GRP‐immunoreactive Neurons in the Rat Suprachiasmatic Nucleus , 1997, The European journal of neuroscience.

[58]  O. Bosler,et al.  Vasoactive intestinal peptide neurons as synaptic targets for vasopressin neurons in the suprachiasmatic nucleus. Double-label immunocytochemical demonstration in the rat , 1999, Neuroscience.

[59]  G. Uhl,et al.  Suprachiasmatic nucleus vasopressin messenger RNA: circadian variation in normal and Brattleboro rats. , 1986, Science.

[60]  F. Jamen,et al.  Dissociation between Light-Induced Phase Shift of the Circadian Rhythm and Clock Gene Expression in Mice Lacking the Pituitary Adenylate Cyclase Activating Polypeptide Type 1 Receptor , 2001, The Journal of Neuroscience.

[61]  H. Romijn,et al.  Immunocytochemical evidence for a diurnal rhythm of neurons showing colocalization of VIP with GRP in the rat suprachiasmatic nucleus , 1998, The Journal of comparative neurology.

[62]  Masaki Tanaka,et al.  Somatostatin neurons form a distinct peptidergic neuronal group in the rat suprachiasmatic nucleus: a double labeling in situ hybridization study , 1996, Neuroscience Letters.

[63]  C. Saper,et al.  Contrasting Effects of Ibotenate Lesions of the Paraventricular Nucleus and Subparaventricular Zone on Sleep–Wake Cycle and Temperature Regulation , 2001, The Journal of Neuroscience.

[64]  R. Leak,et al.  Suprachiasmatic pacemaker organization analyzed by viral transynaptic transport , 1999, Brain Research.

[65]  C. Colwell,et al.  Disrupted circadian rhythms in VIP- and PHI-deficient mice. , 2003, American journal of physiology. Regulatory, integrative and comparative physiology.

[66]  S. T. Inouye,et al.  Photic regulation of peptides located in the ventrolateral subdivision of the suprachiasmatic nucleus of the rat: daily variations of vasoactive intestinal polypeptide, gastrin-releasing peptide, and neuropeptide Y , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[67]  Masaki Tanaka,et al.  Induction of NGFI-A gene expression in the rat suprachiasmatic nucleus by photic stimulation , 1997, Brain Research.

[68]  H. Nishino,et al.  Vasoactive intestinal peptide and gastrin-releasing peptide play distinct roles in the suprachiasmatic nucleus , 1996, Brain Research Bulletin.

[69]  R. V. Sharma,et al.  Molecular Cloning of a Novel Variant of the Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Receptor That Stimulates Calcium Influx by Activation of L-type Calcium Channels* , 1996, The Journal of Biological Chemistry.

[70]  T. Bonner,et al.  Two receptors for vasoactive intestinal polypeptide with similar specificity and complementary distributions. , 1994, Endocrinology.

[71]  Y. Oiso,et al.  Pituitary adenylate cyclase-activating polypeptide stimulates arginine vasopressin release in conscious rats. , 1993, Neuroendocrinology.

[72]  K. Shinohara,et al.  Luminance-dependent decrease in vasoactive intestinal polypeptide in the rat suprachiasmatic nucleus , 1998, Neuroscience Letters.

[73]  H. Marston,et al.  Overexpression of the human VPAC2 receptor in the suprachiasmatic nucleus alters the circadian phenotype of mice. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[74]  Yan Zhu,et al.  A neural circuit for circadian regulation of arousal , 2001, Nature Neuroscience.

[75]  P. Dijkhuizen,et al.  Adenoviral Vector-Mediated Expression of Neurotrophin-3 Increases Neuronal Survival in Suprachiasmatic Nucleus Grafts , 2001, Experimental Neurology.

[76]  G. Fink,et al.  Molecular cloning and expression of a cDNA encoding a receptor for pituitary adenylate cyclase activating polypeptide (PACAP) , 1993, FEBS letters.

[77]  K. Shinohara,et al.  Differential regulation of pituitary adenylate cyclase-activating peptide receptor variants in the rat suprachiasmatic nucleus , 2002, Neuroscience.

[78]  R. Aguilar-Roblero,et al.  Anterior paraventricular thalamus modulates light-induced phase shifts in circadian rhythmicity in rats. , 2002, American journal of physiology. Regulatory, integrative and comparative physiology.

[79]  Joseph S. Takahashi,et al.  Chimera Analysis of the Clock Mutation in Mice Shows that Complex Cellular Integration Determines Circadian Behavior , 2001, Cell.

[80]  Shigenori Watanabe,et al.  Involvement of vasoactive intestinal polypeptide in NMDA-induced phase delay of firing activity rhythm in the suprachiasmatic nucleus in vitro , 1994, Neuroscience & Biobehavioral Reviews.

[81]  P. J. Larsen,et al.  Pituitary Adenylate Cyclase-Activating Peptide (PACAP) in the Retinohypothalamic Tract: A Potential Daytime Regulator of the Biological Clock , 1997, The Journal of Neuroscience.

[82]  S. Shioda,et al.  Pituitary adenylate cyclase-activating polypeptide (PACAP): a novel regulator of vasopressin-containing neurons , 1997, Brain Research.

[83]  R. Leak,et al.  Suprachiasmatic nucleus organization , 2002, Cell and Tissue Research.

[84]  E. Stopa,et al.  Localization of vasoactive intestinal peptide and peptide histidine isoleucine immunoreactivity and mRNA within the rat suprachiasmatic nucleus. , 1988, Brain research.

[85]  D. Cutler,et al.  Vasoactive intestinal polypeptide (VIP) phase‐shifts the rat suprachiasmatic nucleus clock in vitro , 2001, The European journal of neuroscience.

[86]  Rae Silver,et al.  Expression of Period Genes: Rhythmic and Nonrhythmic Compartments of the Suprachiasmatic Nucleus Pacemaker , 2001, The Journal of Neuroscience.

[87]  A. Harmar,et al.  Circadian changes in PACAP type 1 (PAC1) receptor mRNA in the rat suprachiasmatic and supraoptic nuclei , 1998, Brain Research.

[88]  A. Harmar.  An Essential Role for Peptidergic Signalling in the Control of Circadian Rhythms in the Suprachiasmatic Nuclei , 2003, Journal of neuroendocrinology.

[89]  Z. Liposits,et al.  Detection of estrogen receptor-beta messenger ribonucleic acid and 125I-estrogen binding sites in luteinizing hormone-releasing hormone neurons of the rat brain. , 2000, Endocrinology.

[90]  Z. Liposits,et al.  Detection of Estrogen Receptor-β Messenger Ribonucleic Acid and 125I-Estrogen Binding Sites in Luteinizing Hormone-Releasing Hormone Neurons of the Rat Brain. , 2000, Endocrinology.

[91]  A. Kalsbeek,et al.  Direct vasoactive intestinal polypeptide-containing projection from the suprachiasmatic nucleus to spinal projecting hypothalamic paraventricular neurons , 1997, Brain Research.

[92]  O. Ottersen,et al.  PACAP and glutamate are co‐stored in the retinohypothalamic tract , 2000, The Journal of comparative neurology.

[93]  H. Okamura,et al.  Neuronal interaction between VIP and vasopressin neurones in the rat suprachiasmatic nucleus. , 1993, Neuroreport.

[94]  Y. Ueta,et al.  Effects of Centrally Administered Pituitary Adenylate Cyclase-Activating Polypeptide on c-fos Gene Expression and Heteronuclear RNA for Vasopressin in Rat Paraventricular and Supraoptic Nuclei , 1999, Neuroendocrinology.

[95]  S. Shioda,et al.  Localization and gene expression of the receptor for pituitary adenylate cyclase-activating polypeptide in the rat brain , 1997, Neuroscience Research.

[96]  M. Johnson,et al.  Domains determining agonist selectivity in chimaeric VIP2 (VPAC2)/PACAP (PAC1) receptors , 1999, British journal of pharmacology.

[97]  Paolo Sassone-Corsi,et al.  Bimodal regulation of mPeriod promoters by CREB-dependent signaling and CLOCK/BMAL1 activity , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[98]  R. Schrier,et al.  Role of glucocorticoid hormones in arginine vasopressin gene regulation. , 2001, Biochemical and biophysical research communications.

[99]  H. Korf,et al.  The pituitary adenylate cyclase‐activating polypeptide modulates glutamatergic calcium signalling: investigations on rat suprachiasmatic nucleus neurons , 2001, Journal of neurochemistry.

[100]  H. Piggins,et al.  Phase-shifting effects of pituitary adenylate cyclase activating polypeptide on hamster wheel-running rhythms , 2001, Neuroscience Letters.

[101]  Jun Lu,et al.  A Broad Role for Melanopsin in Nonvisual Photoreception , 2003, The Journal of Neuroscience.

[102]  A. Loudon,et al.  Expression of vasoactive intestinal peptide mRNA in the suprachiasmatic nuclei of the circadian tau mutant hamster , 1998, Neuroscience Letters.

[103]  R Teclemariam-Mesbah,et al.  Anatomical demonstration of the suprachiasmatic nucleus–pineal pathway , 1999, The Journal of comparative neurology.

[104]  E G Stopa,et al.  Day-night variation in prepro vasoactive intestinal peptide/peptide histidine isoleucine mRNA within the rat suprachiasmatic nucleus. , 1990, Brain research. Molecular brain research.

[105]  S. Shibata,et al.  Pituitary adenylate cyclase-activating polypeptide produces a phase shift associated with induction of mPer expression in the mouse suprachiasmatic nucleus , 2002, Neuroscience.

[106]  H. Piggins,et al.  The roles of vasoactive intestinal polypeptide in the mammalian circadian clock. , 2003, The Journal of endocrinology.

[107]  J. Penney,et al.  Simultaneous isotopic and nonisotopic in situ hybridization histochemistry with cRNA probes. , 1998, Brain research. Brain research protocols.

[108]  T. Brown,et al.  Effects of Vasoactive Intestinal Polypeptide on Neurones of the Rat Suprachiasmatic Nuclei In Vitro , 2002, Journal of neuroendocrinology.

[109]  Sanbing Shen,et al.  The mouse VPAC2 receptor confers suprachiasmatic nuclei cellular rhythmicity and responsiveness to vasoactive intestinal polypeptide in vitro , 2003, The European journal of neuroscience.

[110]  S. Shioda,et al.  Distribution of PACAP Receptor and Its Splice Variants in the Rat Brain by in Situ RT‐PCR , 2000, Annals of the New York Academy of Sciences.

[111]  A. Kalsbeek,et al.  Printed in U.S.A. Copyright © 2000 by The Endocrine Society Functional Connections between the Suprachiasmatic Nucleus and the Thyroid Gland as Revealed by Lesioning and Viral Tracing Techniques in the Rat , 2022 .

[112]  G. Fink,et al.  The VIP2 receptor: Molecular characterisation of a cDNA encoding a novel receptor for vasoactive intestinal peptide , 1993, FEBS letters.

[113]  J. Hannibal,et al.  Vasoactive intestinal polypeptide induces per1 and per2 gene expression in the rat suprachiasmatic nucleus late at night , 2002, The European journal of neuroscience.

[114]  H. Okamura,et al.  Vasoactive intestinal peptide (VIP)-like immunoreactive neurons located in the rat suprachiasmatic nucleus receive a direct retinal projection , 1989, Neuroscience Letters.