Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, United Kingdom.
Hippocampus. 2012 Mar;22(3):555-76. doi: 10.1002/hipo.20921. Epub 2011 Mar 1.
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 Mg(2+) , 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.
皮层区的震荡网络活动被认为对认知、学习和记忆等生理过程至关重要，也是癫痫等疾病的基础。人们越来越关注 kainate 受体 (KAr) 在网络震荡和同步中的作用。内嗅皮层 (EC) 在学习和记忆中起着关键作用，也是颞叶癫痫中功能障碍的主要部位。KAr 被认为参与了 EC 的震荡发生，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，我们使用大鼠脑片的全细胞膜片钳记录，对内嗅皮层 (EC) 中第 III 层的 KAr 功能进行了详细分析，该层是已知对震荡发生高度敏感的部位。我们证明，含有 GluK1 亚基的 KAr 在第 III 层的锥体神经元上的谷氨酸能突触作为易化性的自受体起作用。此外，含有 GluK1 的 KAr 介导谷氨酸能突触上 GABA 能中间神经元的兴奋性驱动。相比之下，另一种 KAr，可能含有 GluK2 亚基，在锥体神经元上的谷氨酸能突触上介导缓慢的突触后兴奋，并且也可能作为异源受体起作用，促进锥体神经元上抑制性末端的 GABA 释放。减少Mg(2+ )，我们之前已经表明可以在第 III 层产生 KAr 依赖性的缓慢网络震荡，增强谷氨酸和 GABA 的释放。这两种效应部分由 GluK1 包含的 KAr 的增加激活维持。GluK1 包含的自受体的增加激活也导致由 GluK2 包含的受体介导的突触后反应的增强。最后，在低镁条件下，两种递质的自发释放表现出节律性周期性，并且，同样地，这依赖于含有 GluK1 的 KAr。结果表明，KAr 在 EC 网络的多个水平上发挥易化作用，并为在该区域解析这些受体在震荡发生中的作用提供了基础。
