Albus Henk, Vansteensel Mariska J, Michel Stephan, Block Gene D, Meijer Johanna H
Department of Neurophysiology, Leiden University Medical Center, Wassenaarseweg 62, Post Office Box 9604, 2300 RC Leiden, The Netherlands.
Curr Biol. 2005 May 24;15(10):886-93. doi: 10.1016/j.cub.2005.03.051.
Circadian rhythms in mammalian behavior, physiology, and biochemistry are controlled by the central clock of the suprachiasmatic nucleus (SCN). The clock is synchronized to environmental light-dark cycles via the retino-hypothalamic tract, which terminates predominantly in the ventral SCN of the rat. In order to understand synchronization of the clock to the external light-dark cycle, we performed ex vivo recordings of spontaneous impulse activity in SCN slices of the rat.
We observed bimodal patterns of spontaneous impulse activity in the dorsal and ventral SCN after a 6 hr delay of the light schedule. Bisection of the SCN slice revealed a separate fast-resetting oscillator in the ventral SCN and a distinct slow-resetting oscillator in the dorsal SCN. Continuous application of the GABA(A) antagonist bicuculline yielded similar results as cut slices. Short application of bicuculline at different phases of the circadian cycle increased the electrical discharge rate in the ventral SCN but, unexpectedly, decreased activity in the dorsal SCN.
GABA transmits phase information between the ventral and dorsal SCN oscillators. GABA can act excitatory in the dorsal SCN and inhibits neurons in the ventral SCN. We hypothesize that this difference results in asymmetrical interregional coupling within the SCN, with a stronger phase-shifting effect of the ventral on the dorsal SCN than vice versa. A model is proposed that focuses on this asymmetry and on the role of GABA in phase regulation.
哺乳动物行为、生理和生物化学中的昼夜节律由视交叉上核（SCN）的中央时钟控制。该时钟通过视网膜下丘脑束与环境明暗周期同步，视网膜下丘脑束主要终止于大鼠的腹侧SCN。为了理解时钟与外部明暗周期的同步，我们对大鼠SCN切片中的自发冲动活动进行了体外记录。
在光照时间表延迟6小时后，我们观察到背侧和腹侧SCN中自发冲动活动的双峰模式。将SCN切片二等分显示，腹侧SCN中有一个单独的快速重置振荡器，背侧SCN中有一个明显的慢速重置振荡器。持续应用GABA(A)拮抗剂荷包牡丹碱产生的结果与切片相似。在昼夜周期的不同阶段短时间应用荷包牡丹碱会增加腹侧SCN中的放电率，但出乎意料的是，会降低背侧SCN中的活动。
GABA在腹侧和背侧SCN振荡器之间传递相位信息。GABA在背侧SCN中可发挥兴奋性作用，并抑制腹侧SCN中的神经元。我们假设这种差异导致SCN内区域间耦合不对称，腹侧对背侧SCN的相移作用比反之更强。提出了一个关注这种不对称性以及GABA在相位调节中作用的模型。
