Expression of vasoactive intestinal peptide mRNA in the suprachiasmatic nuclei of the circadian tau mutant hamster Robert J. Lucas a, *, Felino R.A. Cagampang b , Andrew S.I. Loudon c , J. Anne Stirland c , Clive W. Coen b a Department of Biology, Imperial College of Science Technology and Medicine, Prince Consort Road, London SW7 2BB, UK b Department of Anatomy and Human Biology, Division of Biomedical Sciences, King’s College, London WC2R 2LS, UK c School of Biological Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK Received 8 April 1997; received in revised form 18 May 1998; accepted 18 May 1998 Abstract The tau mutation of the Syrian hamster is one of only two mutations currently known to affect the circadian system in mammals. In order to investigate the molecular mechanisms associated with this mutation, we have compared the level of expression of the mRNA for vasoactive intestinal peptide (VIP) in the suprachiasmatic nuclei (SCN) and cerebral cortex of homozygous tau mutant and wild-type animals using in situ hybridization histochemistry. We observed no significant circadian variation in this message within the SCN, cingulate cortex or parietal cortex of either genotype. Comparison between genotypes indicated a significantly higher signal for VIP mRNA in the SCN of tau animals. This phenotypic effect within the SCN raises the possibility that some of the circadian consequences of the tau mutation are associated with an increased expression of the VIP gene.  1998 Elsevier Science Ireland Ltd. All rights reserved Keywords: Vasoactive intestinal peptide; Suprachiasmatic nuclei; mRNA; In situ hybridization histochemistry; tau Mutant; Cir- cadian rhythms The circadian rhythms that characterize many physiolo- gical systems in mammals are produced by a clock located in the suprachiasmatic nuclei (SCN) of the anterior hypotha- lamus. The generation of rhythmicity is intrinsic to these nuclei [7]. Synchronization with the light-dark cycle is enabled by projections from the retina [13]. The tau mutation of the Syrian hamster was the first circadian mutation to be discovered in a vertebrate [16]. The most notable phenotypic effect of this single autosomal mutation is a reduction in the period of the circadian rhythm of wheel running from the 24 h typical of wild-types to around 20 h in the homozygous tau mutant [16]. Transplan- tation studies [17] indicate that the altered circadian period of tau mutants is generated within the SCN. These findings have confirmed the importance of the SCN in the circadian system and demonstrated that the tau gene is expressed within these nuclei. The nature and site of the tau gene and its mutation are currently unknown. In order to elucidate the molecular char- acteristics of the tau phenotype we have examined the expression of the gene encoding vasoactive intestinal pep- tide (VIP) in the SCN of tau and wild-type hamsters using in situ hybridization histochemistry. This neuropeptide is abundantly expressed by neurons in the ventral portion of the mammalian SCN [4]; these neurons receive photic infor- mation directly from the retina [10] and indirectly via the intergeniculate leaflet of the lateral geniculate body [9]. In vitro and in vivo studies have indicated that VIP has phase- resetting properties [1,15,19]. This study was carried out using tau mutant and wild-type hamsters maintained as hybrids of LAK/LVG (Charles River, Wilmington, MA, USA) and Wrights (Essex, UK) strains. The background of the original tau hamsters is described by Ralph and Menaker [16] and their subsequent Neuroscience Letters 249 (1998) 147–150 0304-3940/98/$19.00  1998 Elsevier Science Ireland Ltd. All rights reserved PII S0304-3940(98)00421-2 * Corresponding author. Tel.: +44 171 5945451; fax: +44 171 5945449; e-mail r.j.lucas@ic.ac.uk