Pre- and post-synaptic functions of kainate receptors at glutamate and GABA synapses in the rat entorhinal cortex

Pre- and post-synaptic functions of kainate receptors at glutamate and GABA synapses in the rat entorhinal cortex
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DOI:
10.1002/hipo.20921
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发表时间:
2012-03-01
期刊:
影响因子:
3.5
通讯作者:
Jones, Roland S. G.
Jones, Roland S. G.
中科院分区:
医学3区
文献类型:
--
作者:
Chamberlain, Sophie E. L.;Jane, David E.;Jones, Roland S. G.

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皮层区域的振荡网络活动被认为对认知、学习和记忆的生理过程至关重要,并且是癫痫等疾病的基础。红藻氨酸受体(KAr)在网络振荡和同步产生中的作用正受到越来越多的关注。内嗅皮层(EC)在学习和记忆中起着关键作用,并且是颞叶癫痫功能障碍的主要部位。KAr与EC的突触发生有关,但关于KAr在该区域突触传递中的生理作用的信息有限。在这里,我们做一个详细的分析KAr功能在EC的第三层,一个网站已知是非常容易发生,使用全细胞膜片钳记录诱发和自发突触电流在大鼠脑切片。我们表明,KAr含有GluK 1亚基作为易化的自受体在第三层锥体神经元的突触。此外,含有GluK 1的KAr介导GABA能中间神经元上的谷氨酸能突触的兴奋性驱动。相反,一个不同的KAr,这是可能包含的GluK 2-亚基介导一个缓慢的突触后兴奋在主神经元上的突触能突触,也可以作为一个heteroceptor,促进GABA释放在抑制终端的主神经元。减少[Mg 2 +]o,我们以前已经表明,可以在第III层中产生依赖于KAr的缓慢网络振荡,增强谷氨酸和GABA的释放。这两种效应部分地通过增加含GluK 1的KAr的活化来维持。含GluK 1自身受体的激活增加也导致含GluK 2受体介导的突触后反应增强。最后,自发释放的两个发射机显示了一个有节奏的周期性低镁,并再次,这是依赖于GluK 1-含KAr。结果表明,KAr在EC网络中具有多层次的易化功能,为进一步研究这些受体在EC网络中的作用提供了基础。(c)2011 Wiley Periodicals,Inc.
Oscillatory network activity in cortical areas is seen as vital to physiological processes of cognition, learning, and memory, and fundamental to disorders such as epilepsy. Increasing attention is being paid to the role of kainate receptors (KAr) in the generation of network oscillations and synchrony. The entorhinal cortex (EC) plays a key role in learning and memory, and is a major site of dysfunction in temporal lobe epilepsy. KAr have been implicated in oscillogenesis in the EC, but limited information is available concerning the physiological roles of KAr in synaptic transmission in this area. Here, we make a detailed analysis of KAr function in Layer III of the EC, a site known to be highly susceptible to oscillogenesis, using whole-cell patch clamp recording of evoked and spontaneous synaptic currents in rat brain slices. We demonstrate that KAr containing the GluK1-subunit act as facilitatory autoreceptors at glutamatergic synapses on pyramidal neurones in Layer III. In addition, GluK1-containing KAr mediate an excitatory drive at glutamatergic synapses on GABAergic interneurones. In contrast, a different KAr, which is likely to contain the GluK2-subunit mediates a slow postsynaptic excitation at glutamatergic synapses on principal neurones, and may also act as a heteroreceptor, facilitating GABA release at inhibitory terminals on principal neurones. Reducing [Mg2+]o, which we have previously shown can generate KAr-dependent slow network oscillations in Layer III, enhances both glutamate and GABA release. Both effects are partly sustained by increased activation of GluK1-containing KAr. Increased activation of the GluK1-containing autoreceptor also results in an enhancement of the postsynaptic response mediated by GluK2-containing receptors. Finally, spontaneous release of both transmitters shows a rhythmic periodicity in low-Mg, and, again, this is dependent on GluK1-containing KAr. The results show that KAr contribute a facilitatory function at multiple levels in the networks of the EC, and provide a basis for dissecting the role of these receptors in oscillogenesis in this area. (c) 2011 Wiley Periodicals, Inc.