Novak C M, Albers H E
Center for Behavioral Neuroscience, Department of Biology, Georgia State University, PO Box 4010, Atlanta, GA 30302-4010, USA.
Am J Physiol Regul Integr Comp Physiol. 2004 May;286(5):R820-5. doi: 10.1152/ajpregu.00575.2003. Epub 2003 Dec 4.
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.
视交叉上核（SCN）是哺乳动物主要的昼夜节律起搏器，其中绝大多数神经元含有抑制性神经递质γ-氨基丁酸（GABA）。大多数研究GABA在SCN中作用的实验是在夜行性啮齿动物身上进行的。通过向SCN微量注射蝇蕈醇激活GABAA受体，可使夜行性啮齿动物的昼夜活动节律提前，但仅在主观白天期间。重置夜行性啮齿动物昼夜节律起搏器的非光刺激也会在主观白天期间使节律提前。GABA在昼行性动物SCN中的作用以及它与夜行性动物的作用有何不同尚不清楚。在本文所述的研究中，在昼夜循环的不同时间，将GABAA激动剂蝇蕈醇直接微量注射到昼行性无条纹尼罗河草鼠（非洲沼鼠）的SCN区域。结果表明，在草鼠的主观白天期间，GABAA受体激活会导致大幅度的相位延迟。用河豚毒素（TTX）处理并不影响蝇蕈醇诱导相位延迟的能力，这表明蝇蕈醇直接作用于SCN内的起搏细胞。这些数据表明，夜行性和昼行性动物的昼夜节律起搏器对SCN神经元中最丰富的神经化学信号的反应方式相反。这些发现首次证明了昼行性和夜行性动物昼夜节律起搏细胞功能的根本差异。
