GAD67-Mediated GABA synthesis and signaling regulate inhibitory synaptic innervation in the visual cortex
GAD67-Mediated GABA synthesis and signaling regulate inhibitory synaptic innervation in the visual cortex
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DOI：
10.1016/j.neuron.2007.05.015
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发表时间：
2007-06-21
期刊：
影响因子：
16.2
通讯作者：
Huang, Z. Josh
中科院分区：
文献类型：
--
作者：
Chattopadhyaya, Bidisha;Di Cristo, Graziella;Huang, Z. Josh
GABA能抑制回路的发展是由神经活动形成的，但其潜在机制尚不清楚。在这里，我们证明了一个新的功能，GABA在调节GABA能神经支配的青少年大脑，当GABA主要被称为抑制性递质。有条件的敲除的限速合成酶GAD 67在篮状中间神经元在青少年视皮层导致细胞自主缺陷的轴突分支，周围锥体神经元的体周突触的形成，和复杂的神经支配领域;同样的操作没有什么影响，随后的维护体周突触。GABA缺乏的这些影响通过抑制GABA再摄取和GABA受体激动剂来挽救。GAD 67而不是GAD 65的种系敲低表现出类似的缺陷，表明GAD 67在体周神经支配的成熟中的特定作用。由于细胞内GABA水平的调节神经元的活动，我们的研究结果牵连GAD 67介导的GABA合成的抑制性神经支配模式的活动依赖性调节。
The development of GABAergic inhibitory circuits is shaped by neural activity, but the underlying mechanisms are unclear. Here, we demonstrate a novel function of GABA in regulating GABAergic innervation in the adolescent brain, when GABA is mainly known as an inhibitory transmitter. Conditional knockdown of the rate-limiting synthetic enzyme GAD67 in basket interneurons in adolescent visual cortex resulted in cell autonomous deficits in axon branching, perisomatic synapse formation around pyramidal neurons, and complexity of the innervation fields; the same manipulation had little influence on the subsequent maintenance of perisomatic synapses. These effects of GABA deficiency were rescued by suppressing GABA reuptake and by GABA receptor agonists. Germline knockdown of GAD67 but not GAD65 showed similar deficits, suggesting a specific role of GAD67 in the maturation of perisomatic innervation. Since intracellular GABA levels are modulated by neuronal activity, our results implicate GAD67-mediated GABA synthesis in activity-dependent regulation of inhibitory innervation patterns.