Mechanism of bilateral communication in the suprachiasmatic nucleus
Mechanism of bilateral communication in the suprachiasmatic nucleus
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DOI：
10.1111/ejn.12109
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发表时间：
2013-03-01
影响因子：
3.4
通讯作者：
Meijer, Johanna H.
中科院分区：
文献类型：
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作者：
Michel, Stephan;Marek, Roger;Meijer, Johanna H.
视交叉上核（SCN）的中央昼夜节律起搏器是一个双侧对称结构。人们对左右SCN之间的生理机制知之甚少，但SCN神经元之间的同步程度可能对昼夜节律系统的特性产生关键影响。在这项研究中，我们使用电生理工具和钙（Ca2+）成像来检查小鼠SCN中双边信号传导的机制。电刺激一个SCN在对侧SCN中产生的反应具有短延迟（约5ms）和Ca2+依赖性，与动作电位介导的化学突触传递一致。膜片钳记录的受刺激细胞显示兴奋性突触后内向电流（EPSCs），其大小足以引发动作电位。电刺激在所有记录的对侧SCN神经元中约30%诱发了河豚毒素依赖的Ca2+瞬态。反应神经元广泛分布于SCN内，以后SCN密度最高。应用谷氨酸受体拮抗剂后，EPSCs和Ca2+反应显着降低。拮抗剂对其他候选递质受体的应用抑制了某些细胞中的Ca2+反应，但总体而言，这些拮抗剂的影响是可变的。在一项功能分析中，对侧SCN的电刺激产生了对侧SCN多单位活动节律频率的昼夜节律相移。这些相移被谷氨酸受体拮抗剂阻断。综上所述，这些结果暗示谷氨酸是左右SCN之间交流所必需的传递素。
The central circadian pacemaker of the suprachiasmatic nuclei (SCN) is a bilaterally symmetrical structure. Little is known about the physiological mechanisms underlying communication between the left and right SCN and yet the degree of synchronization between SCN neurons can have a critical impact on the properties of the circadian system. In this study, we used electrophysiological tools and calcium (Ca2+) imaging to examine the mechanisms underlying bilateral signaling in mouse SCN. Electrical stimulation of one SCN produced responses in the contralateral SCN with a short delay (approximately 5ms) and Ca2+-dependence that are consistent with action potential-mediated chemical synaptic transmission. Patch-clamp recordings of stimulated cells revealed excitatory postsynaptic inward-currents (EPSCs), which were sufficient in magnitude to elicit action potentials. Electrical stimulation evoked tetrodotoxin-dependent Ca2+ transients in about 30% of all contralateral SCN neurons recorded. The responding neurons were widely distributed within the SCN with a highest density in the posterior SCN. EPSCs and Ca2+ responses were significantly reduced after application of a glutamate receptor antagonist. Application of antagonists for receptors of other candidate transmitters inhibited the Ca2+ responses in some of the cells but overall the impact of these antagonists was variable. In a functional assay, electrical stimulation of the SCN produced phase shifts in the circadian rhythm in the frequency of multiunit activity rhythm in the contralateral SCN. These phase shifts were blocked by a glutamate receptor antagonist. Taken together, these results implicate glutamate as a transmitter required for communication between the left and right SCN.