Slow-decaying presynaptic calcium dynamics gate long-lasting asynchronous release at the hippocampal mossy fiber to CA3 pyramidal cell synapse.

Slow-decaying presynaptic calcium dynamics gate long-lasting asynchronous release at the hippocampal mossy fiber to CA3 pyramidal cell synapse.
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DOI:
10.1002/syn.22178
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发表时间:
2020-12
期刊:
Synapse (New York, N.Y.)
影响因子:
--
通讯作者:
Tóth K
Tóth K
中科院分区:
其他
文献类型:
--
作者:
Chamberland S;Timofeeva Y;Evstratova A;Norman CA;Volynski K;Tóth K

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动作电位触发两种模式的神经递质释放,其中一种是快速同步释放,另一种是暂时延迟的异步释放。异步释放有助于突触的信息传递,包括海马苔藓纤维(MF)到CA3锥体细胞突触,在那里它控制突触后CA3锥体神经元放电的时间。在这里,我们确定并描述了MF-CA3突触异步释放的主要决定因素。我们发现,在重复的中频刺激后,MF - ca3突触的异步释放可以持续数秒。提高刺激频率或外部Ca2+浓度增加了异步释放速率,因此,认为突触前Ca2+动力学是异步释放速率的主要决定因素。直接MF钮扣Ca2+成像显示缓慢的Ca2+衰减动力学动作电位(AP)突发诱发Ca2+瞬态。最后,我们观察到,通过P/Q型电压门控Ca2+通道,Ca2+内流优先介导异步释放,而N型VGCCs的贡献有限。总的来说,我们的研究结果揭示了MF末端长期异步释放的决定因素,并表明异步释放可能影响CA3锥体细胞在颗粒细胞破裂终止后的几秒钟内的放电。MF‐CA3突触的异步释放可以持续数秒,突触前Ca2+动力学是这种释放速率的主要决定因素。异步释放优先由P/Q型电压门控Ca2+通道介导,而N型VGCCs的贡献有限。
Action potentials trigger two modes of neurotransmitter release, with a fast synchronous component and a temporally delayed asynchronous release. Asynchronous release contributes to information transfer at synapses, including at the hippocampal mossy fiber (MF) to CA3 pyramidal cell synapse where it controls the timing of postsynaptic CA3 pyramidal neuron firing. Here, we identified and characterized the main determinants of asynchronous release at the MF–CA3 synapse. We found that asynchronous release at MF–CA3 synapses can last on the order of seconds following repetitive MF stimulation. Elevating the stimulation frequency or the external Ca2+ concentration increased the rate of asynchronous release, thus, arguing that presynaptic Ca2+ dynamics is the major determinant of asynchronous release rate. Direct MF bouton Ca2+ imaging revealed slow Ca2+ decay kinetics of action potential (AP) burst‐evoked Ca2+ transients. Finally, we observed that asynchronous release was preferentially mediated by Ca2+ influx through P/Q‐type voltage‐gated Ca2+ channels, while the contribution of N‐type VGCCs was limited. Overall, our results uncover the determinants of long‐lasting asynchronous release from MF terminals and suggest that asynchronous release could influence CA3 pyramidal cell firing up to seconds following termination of granule cell bursting. Asynchronous release at MF‐CA3 synapses can last on the order of seconds and presynaptic Ca2+ dynamics are the major determinants of this type of release rate. Asynchronous release was preferentially mediated by P/Q‐type voltage‐gated Ca2+ channels, while the contribution of N‐type VGCCs was limited.
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