GABAB Receptor Activation Triggers BDNF Release and Promotes the Maturation of GABAergic Synapses
GABAB Receptor Activation Triggers BDNF Release and Promotes the Maturation of GABAergic Synapses
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DOI：
10.1523/jneurosci.3587-09.2009
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发表时间：
2009-09-16
影响因子：
5.3
通讯作者：
Gaiarsa, Jean-Luc
中科院分区：
文献类型：
--
作者：
Fiorentino, Herve;Kuczewski, Nicola;Gaiarsa, Jean-Luc
GABA是成年人大脑中主要的抑制性神经递质，最近已成为网络发育的重要信号。GABA的营养功能主要是通过激活亲离子型GABA（A）受体使胚胎和新生儿神经元去极化。在这里，我们证明了一种新的机制，内源性GABA选择性地调节发育中的大脑GABA能突触的发展。采用全细胞膜片钳技术记录新生小鼠海马神经元上功能性GABA（B）受体（GABA（B）-Rs）的表达，并对表达GFP标记的脑源性神经营养因子（BDNF）的培养海马神经元进行延时荧光成像，我们发现代谢型GABA（B）受体（GABA（B）-Rs）的激活触发BDNF的分泌，促进新生小鼠海马体周GABA能突触的发育。由于GABA（B）-Rs的激活发生在发育中海马中存在的特征性持续生理网络驱动的突触活动期间，我们的结果揭示了突触活动可以调节发育中大脑中局部GABA能突触连接的发展的新机制。
GABA, the main inhibitory neurotransmitter in the adult brain, has recently emerged as an important signal in network development. Most of the trophic functions of GABA have been attributed to depolarization of the embryonic and neonatal neurons via the activation of ionotropic GABA(A) receptors. Here we demonstrate a novel mechanism by which endogenous GABA selectively regulates the development of GABAergic synapses in the developing brain. Using whole-cell patch-clamp recordings on newborn mouse hippocampilacking functional GABA(B) receptors(GABA(B)-Rs) and time-lapse fluorescence imaging on cultured hippocampal neurons expressing GFP-tagged brain-derived neurotrophic factor ( BDNF), we found that activation of metabotropic GABA(B) receptors (GABA(B)-Rs) triggers secretion of BDNF and promotes the development of perisomatic GABAergic synapses in the newborn mouse hippocampus. Because activation of GABA(B)-Rs occurs during the characteristic ongoing physiological network-driven synaptic activity present in the developing hippocampus, our results reveal a new mechanism by which synaptic activity can modulate the development of local GABAergic synaptic connections in the developing brain.