Novel phase-shifting effects of GABAA receptor activation in the suprachiasmatic nucleus of a diurnal rodent

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2004-05, Vol.286 (5), p.R820-R825
• Main Authors: Novak, C. M, Albers, H. E
• Format: Article
• Language: English
• Subjects: Animals; Circadian Rhythm - physiology; Dose-Response Relationship, Drug; Female; GABA Agonists - pharmacology; Male; Muridae - physiology; Muscimol - pharmacology; Receptors, GABA-A - physiology; Suprachiasmatic Nucleus - drug effects; Suprachiasmatic Nucleus - physiology
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00575.2003

Departments of Biology and Psychology, Center for Behavioral Neuroscience, Georgia State University, Atlanta, Georgia 30302-4010 Submitted 2 October 2003 ; accepted in final form 28 November 2003 The vast majority of neurons in the suprachiasmatic nucleus (SCN), the primary circadian pacemaker in mammals, contain the inhibitory neurotransmitter GABA. Most studies investigating the role of GABA in the SCN have been performed using nocturnal rodents. Activation of GABA A receptors by microinjection of muscimol into the SCN phase advances the circadian activity rhythm of nocturnal rodents, but only during the subjective day. Nonphotic stimuli that reset the circadian pacemaker of nocturnal rodents also produce phase advances during the subjective day. The role of GABA in the SCN of diurnal animals and how it may differ from nocturnal animals is not known. In the studies described here, the GABA A agonist muscimol was microinjected directly into the SCN region of diurnal unstriped Nile grass rats ( Arvicanthis niloticus ) at various times in their circadian cycle. The results demonstrate that GABA A receptor activation produces large phase delays during the subjective day in grass rats. Treatment with TTX did not affect the ability of muscimol to induce phase delays, suggesting that muscimol acts directly on pacemaker cells within the SCN. These data suggest that the circadian pacemakers of nocturnal and diurnal animals respond to the most abundant neurochemical signal found in SCN neurons in opposite ways. These findings are the first to demonstrate a fundamental difference in the functioning of circadian pacemaker cells in diurnal and nocturnal animals. circadian rhythm; muscimol; grass rat; Arvicanthis niloticus ; phase-response curve Address for reprint requests and other correspondence: C. M. Novak, Center for Behavioral Neuroscience, Georgia State Univ., PO Box 4010, Biology Dept., Atlanta, GA 30302-4010 (E-mail: biocmn{at}langate.gsu.edu ).