Spontaneous glutamatergic activity induces a BDNF-dependent potentiation of GABAergic synapses in the newborn rat hippocampus
Spontaneous glutamatergic activity induces a BDNF-dependent potentiation of GABAergic synapses in the newborn rat hippocampus
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DOI：
10.1113/jphysiol.2008.158550
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发表时间：
2008-11-01
影响因子：
5.5
通讯作者：
Gaiarsa, Jean-Luc
中科院分区：
文献类型：
--
作者：
Kuczewski, Nicola;Langlois, Anais;Gaiarsa, Jean-Luc
自发进行的突触活动被认为在神经元回路的成熟中起指导作用。然而，所涉及的突触活动的类型以及这种活动如何转化为结构和功能变化还没有完全了解。在这里，我们表明，正在进行的海马能突触活动触发了一个持久的增强γ-氨基丁酸（GABA）介导的突触活动（LLPGABA-A）在发育中的大鼠海马。LLPGABA-A诱导需要（i）AMPA受体和L型电压依赖性钙通道的激活，（ii）内源性脑源性神经营养因子（BDNF）的释放，和（iii）突触后原肌球蛋白相关激酶受体B（Trk B）的激活。我们发现，自发的海马能活性是维持新生大鼠海马中高水平的天然BDNF所必需的，并且在没有海马能活性的情况下应用外源性BDNF诱导LLPGABA-A。这些结果表明，正在进行的海马神经元能突触活动在海马GABA能突触的功能成熟中起着关键作用，通过涉及BDNF释放和下游信号传导的级联反应，通过突触后TrkB受体激活。
Spontaneous ongoing synaptic activity is thought to play an instructive role in the maturation of the neuronal circuits. However the type of synaptic activity involved and how this activity is translated into structural and functional changes is not fully understood. Here we show that ongoing glutamatergic synaptic activity triggers a long-lasting potentiation of gamma-aminobutyric acid (GABA) mediated synaptic activity (LLPGABA-A) in the developing rat hippocampus. LLPGABA-A induction requires (i) the activation of AMPA receptors and L-type voltage-dependent calcium channels, (ii) the release of endogenous brain-derived neurotrophic factor (BDNF), and (iii) the activation of postsynaptic tropomyosin-related kinase receptors B (TrkB). We found that spontaneous glutamatergic activity is required to maintain a high level of native BDNF in the newborn rat hippocampus and that application of exogenous BDNF induced LLPGABA-A in the absence of glutamatergic activity. These results suggest that ongoing glutamatergic synaptic activity plays a pivotal role in the functional maturation of hippocampal GABAergic synapses by means of a cascade involving BDNF release and downstream signalling through postsynaptic TrkB receptor activation.