Changing properties of GABAA receptor-mediated signaling during early neocortical development
Changing properties of GABAA receptor-mediated signaling during early neocortical development
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DOI：
10.1152/jn.1999.82.2.570
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发表时间：
1999-08-01
影响因子：
2.5
通讯作者：
Kriegstein, AR
中科院分区：
文献类型：
--
作者：
Owens, DF;Liu, XL;Kriegstein, AR
来自几个大脑区域的证据表明，伽马氨基丁酸(GABA)可以在发育过程中发挥营养作用，扩大这种氨基酸的作用，使其超出作为抑制性神经递质的功能。新皮质脑室带(VZ)中的增殖前体细胞和发育中的皮质板(CP)中的未成熟迁移后神经元一样，表达功能性的GABA(A)受体；然而，这些不同细胞群中的GABA(A)受体的推动作用尚未进行比较。在胚胎和出生后早期大脑皮层的电生理技术中，我们发现VZ细胞表达的GABA(A)受体与GABA具有更高的表观亲和力，并且与CP中的神经元相比，对受体脱敏相对不敏感。GABA诱导的电流幅度随着成熟而增加，在VZ的前体细胞的记录中发现的反应最小。没有证据表明VZ细胞上的GABA(A)受体是通过突触激活的，这与以前的数据一致，表明这些受体是通过非突触释放的配体以旁分泌方式激活的。神经元在出生并迁移到CP后，开始表现出自发的突触活动，其中大部分是由GABA(A)介导的。这些自发的GABA(A)突触后电流(SPSCs)在胚胎第18天(E18)首次检测到。出生时，与50%的皮质神经元记录类似，显示GABA(A)介导的sPSCs，且该值随年龄增加而增加。GABA(A)介导的sPSCs是动作电位依赖性的，来源于局部GABA能中间神经元。GABA的应用可以在新生大脑皮层神经元中诱发动作电位依赖性的PSCs，提示在出生后的最初几天，GABA可以作为兴奋性神经递质。最后，出生后早期神经元中也存在N-甲基-D-天冬氨酸(NMDA)介导的sPSCs，但不存在非NMDA介导的sPSCs。在负保持电位(-60 mV至-70 mV)钳制电压的细胞中未观察到这些事件，但当保持电位设置为正值(+30 mV至+60 mV)时明显。总之，这些结果为大脑皮层GABA能通讯的早期成熟以及前体细胞和早期有丝分裂后神经元之间GABA(A)受体特性的功能变化提供了证据。GABA(A)受体特性的改变可能反映了从旁分泌到突触受体激活的转变。
Evidence from several brain regions suggests gamma-aminobutyric acid (GABA) can exert a trophic influence during development, expanding the role of this amino acid beyond its function as an inhibitory neurotransmitter. Proliferating precursor cells in the neocortical ventricular zone (VZ) express functional GABA(A) receptors as do immature postmigratory neurons in the developing cortical plate (CP); however, GABA(A) receptor propel-ties in these distinct cell populations have not been compared. Using electrophysiological techniques in embryonic and early postnatal neocortex, we find that GABA(A) receptors expressed by VZ cells have a higher apparent affinity for GABA and an relatively insensitive to receptor desensitization compared with neurons in the CP. GABA-induced current magnitude increases with maturation with the smallest responses found in recordings from precursor cells in the VZ. No evidence was found that GABA(A) receptors on VZ cells are activated synaptically, consistent with previous data suggesting that these receptors are activated in a paracrine fashion by nonsynaptically released ligand. After neurons are born and migrate to the CP, they begin to demonstrate spontaneous synaptic activity, the majority of which is GABA(A) mediated. These spontaneous GABA(A) postsynaptic currents (sPSCs) first were detected at embryonic day 18 (E18). Al birth, similar to 50% of recordings from cortical neurons demonstrated GABA(A)-mediated sPSCs, and this value increased with age. GABA(A)-mediated sPSCs were action potential dependent and arose from local GABAergic interneurons. GABA application could evoke action potential-dependent PSCs in neonatal cortical neurons, suggesting that during the first few postnatal days, GABA can act as an excitatory neurotransmitter. Finally, N-methyl-D-aspartate (NMDA)- but not non-NMDA-mediated sPSCs were also present in early postnatal neurons. These events were not observed in cells voltage clamped at negative holding potentials (-60 to -70 mV) but were evident when the holding potential was set at positive values (+30 to +60 mV). Together these results provide evidence for the early maturation of GABAergic communication in the neocortex and a functional change in GABA(A)-receptor properties between precursor cells and early postmitotic neurons. The change in GABA(A)-receptor properties may reflect the shift from paracrine to synaptic receptor activation.