Assessing the role of lh channels in synaptic transmission and mossy fiber LTP
Assessing the role of lh channels in synaptic transmission and mossy fiber LTP
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DOI：
10.1073/pnas.142213199
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发表时间：
2002-07-09
影响因子：
11.1
通讯作者：
Castillo, PE
中科院分区：
文献类型：
--
作者：
Chevaleyre, V;Castillo, PE
超极化激活的非选择性阳离子通道（Ih 通道）在控制膜兴奋性和节律性神经元活动中发挥重要作用。然而，突触前 Ih 通道在调节突触功能中的功能相关性尚未明确。最近，有人提出 [Mellor, J., Nicoll, R. A. & Schmitz, D. (2002) Science 295, 143-147] 突触前 Ih 通道对于海马苔藓纤维长时程增强 (LTP) 是必需的。这一观察结果对另一种模型提出了挑战，该模型表明突触前形式的 LTP 是由递质释放机制的直接修改引起的。在这里，我们评估了 Ih 在海马苔藓纤维 LTP 以及小脑平行纤维 LTP 中的作用，这两种增强形式具有共同的机制。我们的结果表明，封锁 1 小时后，苔藓纤维 LTP 和平行纤维 LTP 均不受影响。此外，Ih 不会显着改变海马中的基础兴奋性突触传递，而有机 Ih 阻滞剂 ZD7288 和 DK-AH 269 会诱导大量的 Ih 独立的突触传递抑制。总之，我们的结果表明 Ih 介导的突触前兴奋性持续变化并不是突触前形式 LTP 的基础。
Hyperpolarization-activated nonselective cation channels (Ih channels) play an important role in the control of membrane excitability and rhythmic neuronal activity. The functional relevance of presynaptic Ih channels in regulating synaptic function, however, is not well established. Recently, it has been proposed [Mellor, J., Nicoll, R. A. & Schmitz, D. (2002) Science 295, 143-147] that presynaptic Ih channels are necessary for hippocampal mossy fiber long-term potentiation (LTP). This observation challenges an alternative model that suggests presynaptic forms of LTP are caused by a direct modification of the transmitter release machinery. Here, we assess the role of Ih in hippocampal mossy fiber LTP as well as cerebellar parallel fiber LTP, forms of potentiation that share common mechanisms. Our results show that after Ih blockade neither mossy fiber LTP nor parallel fiber LTP are affected. Furthermore, Ih does not significantly modify basal excitatory synaptic transmission in the hippocampus, whereas the organic Ih blockers ZD7288 and DK-AH 269 induce a large Ih-independent depression of synaptic transmission. In summary, our results indicate that Ih-mediated persistent changes in presynaptic excitability do not underlie presynaptic forms of LTP.