Department of Physiology and Neurobiology, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
Cereb Cortex. 2011 Aug;21(8):1792-802. doi: 10.1093/cercor/bhq247. Epub 2010 Dec 8.
During rodent corticogenesis, a sizeable subpopulation of γ-aminobutyric acid (GABA)ergic interneurons arises extracortically from the medial ganglionic eminence (MGE). These neurons progressively acquire responsiveness to GABA in the course of corticopetal tangential migration, a process regulated by ambient GABA and mediated by GABA(A) receptors. Here, we combined patch clamp electrophysiology and single-cell reverse transcription-polymerase chain reaction to examine GABA(A) receptor expression in green fluorescent MGE-derived (eGFP+) cells in telencephalic slices from gestational day 14.5 BAC-Lhx6 embryos. GABA concentration-response curves revealed lower apparent affinity and efficacy in eGFP+ cells in and around the MGE than their counterparts in the cortex. Pharmacological tests revealed subunit-selective response profiles in the MGE and cortex consistent with differential expression of GABA(A) receptor isoforms. Profiling of GABA(A) receptor subunit transcripts (α1-5, β1-3, and γ1-3, δ) uncovered increased expression of the α1-, α2-, α5-, γ2-, and γ3-subunit messenger RNAs in the cortex. We propose that the dynamic expression of certain GABA(A) receptor subunits contributes to assembling receptor isoforms that confer functional attributes important in regulating the migration and maturation of primordial GABAergic cortical interneurons.
在啮齿动物皮质发生过程中，相当一部分γ-氨基丁酸（GABA）能中间神经元从内侧神经节隆起（MGE）向外皮质起源。这些神经元在皮质投射性切线迁移过程中逐渐对 GABA 产生反应，这一过程受周围 GABA 的调节，并由 GABA(A)受体介导。在这里，我们结合膜片钳电生理学和单细胞逆转录聚合酶链反应，在从胚胎第 14.5 天 BAC-Lhx6 胚胎的端脑切片中检查绿色荧光 MGE 衍生（eGFP+）细胞中的 GABA(A)受体表达。GABA 浓度反应曲线显示，MGE 内和周围的 eGFP+细胞的表观亲和力和效力低于皮质中的对应细胞。药理学测试显示 MGE 和皮质中的亚基选择性反应谱与 GABA(A)受体亚型的差异表达一致。GABA(A)受体亚基转录本（α1-5、β1-3 和 γ1-3、δ）的分析显示，在皮质中α1-、α2-、α5-、γ2-和γ3-亚基信使 RNA 的表达增加。我们提出，某些 GABA(A)受体亚基的动态表达有助于组装赋予调节原始 GABA 能皮质中间神经元迁移和成熟的重要功能属性的受体同工型。
