title: Tetrodotoxin administration in the suprachiasmatic nucleus prevents NMDA-induced reductions in pineal melatonin without influencing Per1 and Per2 mRNA levels.
abstract: The suprachiasmatic nucleus (SCN) of the anterior hypothalamus contains a light-entrainable circadian pacemaker. Neurons in the SCN are part of a circuit that conveys light information from retinal efferents to the pineal gland. Light presented during the night acutely increases mRNA levels of the circadian clock genes Per1 and Per2 in the SCN, and acutely suppresses melatonin levels in the pineal gland. The present study investigated whether the ability of light to increase Per1 and Per2 mRNA levels and suppress pineal melatonin levels requires sodium-dependent action potentials in the SCN. Per1 and Per2 mRNA levels in the SCN and pineal melatonin levels were measured in Syrian hamsters injected with tetrodotoxin (TTX) prior to light exposure or injection of N-methyl-D-aspartate (NMDA). TTX inhibited the ability of light to increase Per1 and Per2 mRNA levels and suppress pineal melatonin levels. TTX did not, however, influence the ability of NMDA to increase Per1 and Per2 mRNA levels, though it did inhibit the ability of NMDA to suppress pineal melatonin levels. These results demonstrate that action potentials in the SCN are not necessary for NMDA receptor activation to increase Per1 and Per2 mRNA levels, but are necessary for NMDA receptor activation to decrease pineal melatonin levels. Taken together, these data support the hypothesis that the mechanism through which light information is conveyed to the pacemaker in the SCN is separate from and independent of the mechanism through which light information is conveyed to the SCN cells whose efferents suppress pineal melatonin levels.
authors.affiliation: Center for Behavioural Neuroscience, and Department of Biology, Georgia State University, Atlanta, 30303, USA. k-paul@northwestern.edu
authors.forename: Ketema N
authors.initials: KN
authors.lastname: Paul
authors.forename: Karen L
authors.initials: KL
authors.lastname: Gamble
authors.forename: Chiaki
authors.initials: C
authors.lastname: Fukuhara
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Novak
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tosini
authors.forename: H Elliott
authors.initials: HE
authors.lastname: Albers
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D018797:Cell Cycle Proteins; D006224:Cricetinae; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D017403:In Situ Hybridization / Q000379:methods; D008029:Lighting / Q000379:methods; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D008647:Mesocricetus; D009043:Motor Activity / Q000187:drug effects / Q000528:radiation effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D056950:Period Circadian Proteins; D010870:Pineal Gland / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay / Q000379:methods; D013493:Suprachiasmatic Nucleus / Q000187:drug effects*; D013779:Tetrodotoxin / Q000008:administration & dosage* / Q000494:pharmacology; D014157:Transcription Factors
chemical_list: D000779:Anesthetics, Local; D018797:Cell Cycle Proteins; D018690:Excitatory Amino Acid Agonists; D009687:Nuclear Proteins; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D008550:Melatonin