Functional role of ambient GABA in refining neuronal circuits early in postnatal development.
Functional role of ambient GABA in refining neuronal circuits early in postnatal development.
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DOI：
10.3389/fncir.2013.00136
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发表时间：
2013
影响因子：
3.5
通讯作者：
Cherubini E
中科院分区：
文献类型：
--
作者：
Cellot G;Cherubini E
在发育早期，γ-氨基丁酸 (GABA) 是成熟大脑中的主要抑制性神经递质，通过向外定向的氯化物通量来去极化和兴奋目标神经元，这是由于阳离子氯化物输入器 NKCC1 和挤出器 KCC2 之间的特殊平衡造成的。出生时 KCC2 的低表达导致细胞内氯离子的积累，并导致相对于静息膜电位的氯离子平衡电位呈阳性。 GABA 通过突触和突触外 GABAA 受体分别介导相性和强直性抑制来发挥作用。在此，我们回顾了有关“环境”GABA 对未成熟大脑中神经元回路细化的贡献的最新数据。我们特别关注海马体，在形成传统突触之前，生长锥和星形胶质细胞以不依赖于钙和 SNARE（可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体）的方式释放 GABA，扩散出去以旁分泌方式激活位于远端神经元的突触外受体。 GABA 去极化作用后细胞内钙的短暂增加导致 DNA 合成和细胞增殖的抑制。补品 GABA 还对细胞迁移发挥趋化作用。随后，当突触形成时，GABA从邻近突触溢出，主要作用于含有GABAA受体亚基的突触外α5、β2、β3和γ，提供主细胞到达产生内在爆发的窗口所必需的膜去极化。这些有助于触发与网络驱动的巨大去极化电位相关的钙瞬变，这些去极化电位充当一致的检测器信号，以增强新兴 GABA 能和谷氨酸能突触的突触功效。
Early in development, γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the mature brain, depolarizes and excites targeted neurons by an outwardly directed flux of chloride, resulting from the peculiar balance between the cation-chloride importer NKCC1 and the extruder KCC2. The low expression of KCC2 at birth leads to accumulation of chloride inside the cell and to the equilibrium potential for chloride positive respect to the resting membrane potential. GABA exerts its action via synaptic and extrasynaptic GABAA receptors mediating phasic and tonic inhibition, respectively. Here, recent data on the contribution of “ambient” GABA to the refinement of neuronal circuits in the immature brain have been reviewed. In particular, we focus on the hippocampus, where, prior to the formation of conventional synapses, GABA released from growth cones and astrocytes in a calcium- and SNARE (soluble N-ethylmaleimide-sensitive-factor attachment protein receptor)-independent way, diffuses away to activate in a paracrine fashion extrasynaptic receptors localized on distal neurons. The transient increase in intracellular calcium following the depolarizing action of GABA leads to inhibition of DNA synthesis and cell proliferation. Tonic GABA exerts also a chemotropic action on cell migration. Later on, when synapses are formed, GABA spilled out from neighboring synapses, acting mainly on extrasynaptic α5, β2, β3, and γ containing GABAA receptor subunits, provides the membrane depolarization necessary for principal cells to reach the window where intrinsic bursts are generated. These are instrumental in triggering calcium transients associated with network-driven giant depolarizing potentials which act as coincident detector signals to enhance synaptic efficacy at emerging GABAergic and glutamatergic synapses.
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影响因子：
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