Developmental decrease in synaptic facilitation at the mouse hippocampal mossy fibre synapse
Developmental decrease in synaptic facilitation at the mouse hippocampal mossy fibre synapse
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DOI：
10.1113/jphysiol.2003.045948
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发表时间：
2003-11-15
影响因子：
5.5
通讯作者：
Takahashi, T
中科院分区：
文献类型：
--
作者：
Mori-Kawakami, F;Kobayashi, K;Takahashi, T
海马苔藓纤维(MF)-CA3锥体细胞突触的传递具有突出的活动依赖性促进作用，被认为在海马信息流中提供了广泛的动态范围。在小鼠出生后3周（3W）至9周（9W）期间，该突触成对脉冲促进和频率依赖性促进的强度显著降低。在此期间，单一EPSCs的平均振幅和方差保持不变。通过改变细胞外Ca2+/Mg2+浓度，配对脉冲比可以改变到与发育期间观察到的相似程度。然而，这伴随着EPSC振幅的30倍以上的变化，表明促进比的发育变化不能简单地用释放概率的变化来解释。在配对脉冲刺激下，使用mag-fura-5监测MF末端的Ca2+瞬态，显示出小的促进作用，但其幅度在3W和9W小鼠之间保持相似。使用CNQX、腺苷、LY341495、H-7或KN-62进行的药理学试验表明，突触前受体（kainate、腺苷和代谢性谷氨酸）和蛋白激酶都不是促进发育变化的原因。然而，与9W小鼠相比，加载膜透性形式的BAPTA对3W小鼠配对脉冲促进的减弱程度要大得多，导致年龄差异明显缩小。这些结果表明，MF突触促进的发育减少是由与残留Ca2+相关的变化引起的，残留Ca2+本身的减少或参与促进的Ca2+结合位点的变化。发育过程中易化比的下降降低了MF传递的动态范围，可能有助于海马回路的稳定。
Transmission at the hippocampal mossy fibre (MF)-CA3 pyramidal cell synapse is characterized by prominent activity-dependent facilitation, which is thought to provide a wide dynamic range in hippocampal informational flow. At this synapse in mice the magnitude of paired-pulse facilitation and frequency-dependent facilitation markedly decreased with postnatal development from 3 weeks (3W) to 9 weeks (9W). Throughout this period the mean amplitude and variance of unitary EPSCs stayed constant. By altering extracellular Ca2+/Mg2+ concentrations the paired-pulse ratio could be changed to a similar extent as observed during development. However, this was accompanied by an over 30-fold change in EPSC amplitude, suggesting that the developmental change in facilitation ratio cannot simply be explained by a change in release probability. With paired-pulse stimulation the Ca2+ transients at MF terminals, monitored using mag-fura-5, showed a small facilitation, but its magnitude remained similar between 3W and 9W mice. Pharmacological tests using CNQX, adenosine, LY341495, H-7 or KN-62 suggested that neither presynaptic receptors (kainate, adenosine and metabotropic glutamate) nor protein kinases are responsible for the developmental change in facilitation. Nevertheless, loading the membrane-permeable form of BAPTA attenuated the paired-pulse facilitation in 3W mice to a much greater extent than in 9W mice, resulting in a marked reduction in age difference. These results suggest that the developmental decrease in the MF synaptic facilitation arises from a change associated with residual Ca2+, a decrease in residual Ca2+ itself or a change in Ca2+-binding sites involved in the facilitation. A developmental decline in facilitation ratio reduces the dynamic range of MF transmission, possibly contributing to the stabilization of hippocampal circuitry.