Kainate Receptor-Dependent Short-Term Plasticity of Presynaptic Ca2+ Influx at the Hippocampal Mossy Fiber Synapses
Kainate Receptor-Dependent Short-Term Plasticity of Presynaptic Ca2+ Influx at the Hippocampal Mossy Fiber Synapses
复制标题
海马苔藓纤维突触突触前 Ca2 流入的红藻氨酸受体依赖性短期可塑性
作者：
H. Kamiya;S. Ozawa;T. Manabe
海马苔藓纤维 (MF)-CA3 突触处的递质释放表现出强大的依赖于使用的短期可塑性，具有极宽的动态范围。最近的研究表明，突触前红藻氨酸受体（KAR）专门位于 MF 轴突上，与残余 Ca2+ 的作用相一致，在该特定突触处介导异常大的促进作用。然而，目前尚不清楚红藻氨酸自身受体的激活如何以活性依赖性方式增强递质释放。使用海马切片中突触前 Ca2+ 和电压的荧光记录，我们证明配对脉冲刺激（间隔为 20-200 毫秒）导致 Ca2+ 流入 MF 末端，而不是其他突触，例如 Schaffer 侧支 -CA1 突触。这些观察结果偏离了典型的残留 Ca2+ 促进假设，假设每个动作电位有等量的 Ca2+ 流入。药理学实验表明，突触前 Ca2+ 流入的促进是由 KAR 的激活介导的。我们还发现 MF 轴突的动作电位伴随着显着的后去极化，这部分是由 KAR 的激活介导的。值得注意的是，后去极化的时间过程近似于成对脉冲促进 Ca2+ 内流的时间过程，表明这两个过程彼此密切相关。这些结果表明，放大突触前 Ca2+ 流入的新机制可能是海马 MF-CA3 突触处强大的短期突触可塑性的基础，这一过程是由 KAR 介导的，KAR 的激活会引起 MF 轴突的显着后去极化，从而增强动作电位驱动的 Ca2+ 流入突触前末梢。
Transmitter release at the hippocampal mossy fiber (MF)–CA3 synapse exhibits robust use-dependent short-term plasticity with an extremely wide dynamic range. Recent studies revealed that presynaptic kainate receptors (KARs), which specifically localized on the MF axons, mediate unusually large facilitation at this particular synapse in concert with the action of residual Ca2+. However, it is currently unclear how activation of kainate autoreceptors enhances transmitter release in an activity-dependent manner. Using fluorescence recordings of presynaptic Ca2+ and voltage in hippocampal slices, here we demonstrate that paired-pulse stimulation (with 20–200 msec intervals) resulted in facilitation of Ca2+ influx into the MF terminals, as opposed to other synapses, such as the Schaffer collateral–CA1 synapse. These observations deviate from typical residual Ca2+hypothesis of facilitation, assuming an equal amount of Ca2+ influx per action potential. Pharmacological experiments reveal that the facilitation of presynaptic Ca2+ influx is mediated by activation of KARs. We also found that action potentials of MF axons are followed by prominent afterdepolarization, which is partly mediated by activation of KARs. Notably, the time course of the afterdepolarization approximates to that of the paired-pulse facilitation of Ca2+influx, suggesting that these two processes are closely related to each other. These results suggest that the novel mechanism amplifying presynaptic Ca2+ influx may underlie the robust short-term synaptic plasticity at the MF–CA3 synapse in the hippocampus, and this process is mediated by KARs whose activation evokes prominent afterdepolarization of MF axons and thereby enhances action potential-driven Ca2+ influx into the presynaptic terminals.
DOI：
10.1073/pnas.88.2.380
发表时间：
1991-01-01
影响因子：
11.1
作者：
JACKSON, MB;KONNERTH, A;AUGUSTINE, GJ
通讯作者：
AUGUSTINE, GJ
影响因子：
56.9
作者：
ZALUTSKY, RA;NICOLL, RA
通讯作者：
NICOLL, RA