Glycine receptors mediate excitation of subplate neurons in neonatal rat cerebral cortex
Glycine receptors mediate excitation of subplate neurons in neonatal rat cerebral cortex
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DOI：
10.1152/jn.00657.2007
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发表时间：
2008-08-01
影响因子：
2.5
通讯作者：
Luhmann, H. J.
中科院分区：
文献类型：
--
作者：
Kilb, W.;Hanganu, I. L.;Luhmann, H. J.
大脑皮层的发育取决于遗传因素和形成不成熟神经元网络的早期电活动模式。板下神经元 (SPn) 参与丘脑皮质神经支配的构建、振荡网络活动的产生以及皮质柱状结构的正确形成。由于甘氨酸受体在早期皮质生成过程中发挥着重要作用，因此我们使用全细胞和穿孔膜片钳记录，分析了从出生后第 0 天 (P0) 到 P4 大鼠的新皮质切片中视觉识别的 SPn 中甘氨酸受体激活的功能后果。在所有 SPn 中，甘氨酸能激动剂甘氨酸、β-丙氨酸和牛磺酸诱导剂量依赖性内向电流，对甘氨酸的亲和力高于对 β-丙氨酸和牛磺酸的亲和力。甘氨酸诱导的反应可被甘氨酸拮抗剂马钱子碱阻断，但不受 GABA 能拮抗剂加巴嗪、N-甲基-D-天冬氨酸受体拮抗剂 D-2-氨基-5-膦基戊酸或印防己毒素和氰基三苯硼酸盐（分别是 α 同聚和含 α(1) 亚基甘氨酸受体的拮抗剂）的影响。在穿孔贴片条件下，甘氨酸诱导膜去极化，足以触发大多数细胞的动作电位（AP）。此外，甘氨酸和牛磺酸降低了注射电流以及引发 AP 所需的突触刺激强度，表明甘氨酸受体对 SPn 具有一致的兴奋作用。牛磺酸转运的抑制和低渗溶液的应用诱导士的宁敏感的内向电流，表明牛磺酸可以作为 SPn 的可能的内源性激动剂。总之，这些结果表明 SPn 表达甘氨酸受体，在出生后早期发育期间介导强烈的兴奋性膜反应。
The development of the cerebral cortex depends on genetic factors and early electrical activity patterns that form immature neuronal networks. Subplate neurons (SPn) are involved in the construction of thalamocortical innervation, generation of oscillatory network activity, and in the proper formation of the cortical columnar architecture. Because glycine receptors play an important role during early corticogenesis, we analyzed the functional consequences of glycine receptor activation in visually identified SPn in neocortical slices from postnatal day 0 (P0) to P4 rats using whole cell and perforated patch-clamp recordings. In all SPn the glycinergic agonists glycine, beta-alanine, and taurine induced dose-dependent inward currents with the affinity for glycine being higher than that for beta-alanine and taurine. Glycine-induced responses were blocked by the glycinergic antagonist strychnine, but were unaffected by either the GABAergic antagonist gabazine, the N-methyl-D-aspartate-receptor antagonist D-2-amino-5-phosphonopentanoic acid, or picrotoxin and cyanotriphenylborate, antagonists of alpha-homomeric and alpha(1)-subunit-containing glycine receptors, respectively. Under perforated-patch conditions, glycine induced membrane depolarizations that were sufficient to trigger action potentials (APs) in most cells. Furthermore, glycine and taurine decreased the injection currents as well as the synaptic stimulation strength required to elicit APs, indicating that glycine receptors have a consistent excitatory effect on SPn. Inhibition of taurine transport and application of hypoosmolar solutions induced strychnine-sensitive inward currents, suggesting that taurine can act as a possible endogenous agonist on SPn. In summary, these results demonstrate that SPn express glycine receptors that mediate robust excitatory membrane responses during early postnatal development.