GABAergic interneurons facilitate mossy fiber excitability in the developing hippocampus
GABAergic interneurons facilitate mossy fiber excitability in the developing hippocampus
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DOI：
10.1523/jneurosci.4672-06.2007
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发表时间：
2007-02-07
影响因子：
5.3
通讯作者：
Manabe, Toshiya
中科院分区：
文献类型：
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作者：
Nakamura, Michiko;Sekino, Yuko;Manabe, Toshiya
在海马苔藓纤维突触的深刻的活动依赖性突触易化是一个独特的和功能上重要的属性。虽然突触前离子型受体，如红藻氨酸受体，有助于部分促进海马，突触前调节的内源性神经递质的确切机制仍不清楚。在这项研究中，我们报告苔藓纤维上的轴突GABA（A）受体参与发育过程中的活动依赖性易化。在未成熟的小鼠海马切片，短列车刺激（5个脉冲，25 Hz）引起的频率依赖性促进不仅突触后反应，但也突触前纤维凌空，代表突触前活动。选择性GABA（A）受体拮抗剂或选择性抑制中间神经元兴奋性的脑啡肽可抑制这种纤维齐射易化。此外，我们直接证明了这种便利化是由使用电压敏感染料的成像实验中苔藓纤维的去极化引起的。这种增加的苔藓纤维兴奋性所造成的去极化作用的GABA逐渐减少与发展，并最终消失在出生后30天左右。这些结果表明，从中间神经元释放的GABA作用于苔藓纤维上的轴突GABA（A）受体，并至少部分地参与了海马的活动和年龄依赖性易化。
Profound activity-dependent synaptic facilitation at hippocampal mossy fiber synapses is a unique and functionally important property. Although presynaptic ionotropic receptors, such as kainate receptors, contribute partially to the facilitation in the hippocampus, the precise mechanisms of presynaptic regulation by endogenous neurotransmitters remain unclear. In this study, we report that axonal GABA(A) receptors on mossy fibers are involved in the activity-dependent facilitation during development. In immature mouse hippocampal slices, short-train stimulation (five pulses at 25 Hz) caused frequency-dependent facilitation of not only postsynaptic responses but also presynaptic fiber volleys that represent presynaptic activities. This fiber volley facilitation was inhibited by selective GABA(A) receptor antagonists, or by enkephalin that selectively suppresses excitability of interneurons. Furthermore, we directly demonstrated that this facilitation resulted from depolarization of mossy fibers in imaging experiments using a voltage-sensitive dye. This increased mossy fiber excitability caused by depolarizing action of GABA gradually decreased with development and eventually disappeared at around postnatal day 30. These results suggested that GABA released from interneurons acted on axonal GABA(A) receptors on mossy fibers and contributed at least partially to the activity-and age-dependent facilitation in the hippocampus.