Neuroscience Center and Department of Biosciences, University of Helsinki, Finland.
J Neurophysiol. 2010 Sep;104(3):1696-706. doi: 10.1152/jn.00840.2009. Epub 2010 Jul 21.
Kainate receptors (KARs) are expressed at high levels in the brain during early development and may be critical for the proper development of neuronal networks. Here we elucidated a physiological role of high-affinity KARs in developing hippocampal network by studying the effects of 25-100 nM kainate (KA) on intrinsic network activity in slice preparations. Whereas 100 nM KA resulted in hyperexcitability of the network and the disruption of natural activity patterns, ≤ 50 nM KA concentrations enhanced the initiation of network bursts yet preserved the characteristic patterns of endogenous activity. This was not dependent on changes in GABAergic transmission or on activation of GluK1 subunit containing KARs. However, the activation of high-affinity KARs increased glutamatergic drive by promoting spontaneous firing of CA3 pyramidal neurons without affecting action potential independent glutamate release. This was not because of changes in the intrinsic somatic properties of pyramidal neurons but seemed to reside in an electrically remote site, most probably in an axonal compartment. Although application of KAR agonists has mainly been used to study pathological type of network activities, this study provides a novel mechanism by which endogenous activity of KARs can modulate intrinsic activities of the emerging neuronal network in a physiologically relevant manner. The results support recent studies that KARs play a central role in the activity-dependent maturation of synaptic circuitries.
kainate 受体 (KARs) 在大脑发育早期高水平表达，对于神经元网络的正常发育可能至关重要。在这里，我们通过研究 25-100 nM kainate (KA) 对切片制备中固有网络活动的影响，阐明了高亲和力 KARs 在发育中的海马网络中的生理作用。虽然 100 nM KA 导致网络过度兴奋和自然活动模式的破坏，但 ≤ 50 nM KA 浓度增强了网络爆发的起始，同时保留了内源性活动的特征模式。这与 GABA 能传递的变化或 GluK1 亚基组成的 KARs 的激活无关。然而，高亲和力 KARs 的激活通过促进 CA3 锥体神经元的自发放电增加了谷氨酸能驱动，而不影响动作电位独立的谷氨酸释放。这不是因为锥体神经元的固有体性质发生了变化，而是似乎存在于电远处的部位，最有可能在轴突区室中。尽管 KAR 激动剂的应用主要用于研究网络活动的病理性类型，但本研究提供了一种新的机制，即内源性 KAR 活性可以以生理相关的方式调节新兴神经元网络的固有活性。这些结果支持了最近的研究，即 KARs 在突触回路的活动依赖性成熟中发挥核心作用。
