Kidd F L, Isaac J T
MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, UK.
Nature. 1999 Aug 5;400(6744):569-73. doi: 10.1038/23040.
Most of the fast excitatory synaptic transmission in the mammalian brain is mediated by ionotrophic glutamate receptors, of which there are three subtypes: AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate), NMDA (N-methyl-D-aspartate) and kainate. Although kainate-receptor subunits (GluR5-7, KA1 and 2) are widely expressed in the mammalian central nervous system, little is known about their function. The development of pharmacological agents that distinguish between AMPA and kainate receptors has now allowed the functions of kainate receptors to be investigated. The modulation of synaptic transmission by kainate receptors and their synaptic activation in a variety of brain regions have been reported. The expression of kainate receptor subunits is developmentally regulated but their role in plasticity and development is unknown. Here we show that developing thalamocortical synapses express postsynaptic kainate receptors as well as AMPA receptors; however, the two receptor subtypes do not colocalize. During the critical period for experience-dependent plasticity, the kainate-receptor contribution to transmission decreases; a similar decrease occurs when long-term potentiation is induced in vitro. This indicates that during development there is activity-dependent regulation of the expression of kainate receptors at thalamocortical synapses.
在哺乳动物大脑中,大多数快速兴奋性突触传递是由离子型谷氨酸受体介导的,该受体有三种亚型:AMPA(α-氨基-3-羟基-5-甲基-4-异恶唑丙酸)、NMDA(N-甲基-D-天冬氨酸)和海人藻酸。尽管海人藻酸受体亚基(GluR5-7、KA1和KA2)在哺乳动物中枢神经系统中广泛表达,但其功能却鲜为人知。能够区分AMPA受体和海人藻酸受体的药物的开发,使得对海人藻酸受体的功能研究成为可能。据报道,海人藻酸受体可调节突触传递,并在多种脑区发生突触激活。海人藻酸受体亚基的表达受发育调控,但其在可塑性和发育过程中的作用尚不清楚。在此我们表明,发育中的丘脑皮质突触既表达突触后海人藻酸受体,也表达AMPA受体;然而,这两种受体亚型并不共定位。在依赖经验的可塑性关键期,海人藻酸受体对传递的贡献降低;在体外诱导长时程增强时也会出现类似的降低。这表明在发育过程中,丘脑皮质突触处海人藻酸受体的表达存在活动依赖性调节。