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Slow-decaying presynaptic calcium dynamics gate long-lasting asynchronous release at the hippocampal mossy fiber to CA3 pyramidal cell synapse.
SYNAPSE ( IF 1.6 ) Pub Date : 2020-06-29 , DOI: 10.1002/syn.22178 Simon Chamberland 1 , Yulia Timofeeva 2, 3, 4 , Alesya Evstratova 1 , Christopher A Norman 5 , Kirill Volynski 4 , Katalin Tóth 6
SYNAPSE ( IF 1.6 ) Pub Date : 2020-06-29 , DOI: 10.1002/syn.22178 Simon Chamberland 1 , Yulia Timofeeva 2, 3, 4 , Alesya Evstratova 1 , Christopher A Norman 5 , Kirill Volynski 4 , Katalin Tóth 6
Affiliation
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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.
中文翻译：
缓慢衰减的突触前钙动力学控制着海马苔藓纤维向CA3锥体细胞突触的长期异步释放。
动作电位触发神经递质释放的两种模式，具有快速同步成分和暂时延迟的异步释放。异步释放有助于信息在突触，包括海马苔藓纤维（MF）到CA3锥体细胞突触的信息传递，在该处它控制突触后CA3锥体神经元激发的时间。在这里，我们确定并表征了MF-CA3突触中异步释放的主要决定因素。我们发现，在反复进行MF刺激后，MF-CA3突触的异步释放可以持续几秒钟。升高刺激频率或外部Ca 2+浓度会增加异步释放的速率，因此认为突触前Ca 2+动态是异步释放速率的主要决定因素。直接MF bouton Ca 2+成像显示，动作电位（AP）诱发的Ca 2+瞬变的Ca 2+衰减动力学较慢。最后，我们观察到异步释放优先由通过P / Q型电压门控Ca 2+通道的Ca 2+流入介导，而N型VGCC的贡献是有限的。总体而言，我们的研究结果揭示了从MF终端持续长时间异步释放的决定因素，并表明异步释放可能会在颗粒细胞爆发终止后的数秒内影响CA3锥体细胞的发射。
更新日期：2020-06-29
中文翻译：
缓慢衰减的突触前钙动力学控制着海马苔藓纤维向CA3锥体细胞突触的长期异步释放。
动作电位触发神经递质释放的两种模式，具有快速同步成分和暂时延迟的异步释放。异步释放有助于信息在突触，包括海马苔藓纤维（MF）到CA3锥体细胞突触的信息传递，在该处它控制突触后CA3锥体神经元激发的时间。在这里，我们确定并表征了MF-CA3突触中异步释放的主要决定因素。我们发现，在反复进行MF刺激后，MF-CA3突触的异步释放可以持续几秒钟。升高刺激频率或外部Ca 2+浓度会增加异步释放的速率，因此认为突触前Ca 2+动态是异步释放速率的主要决定因素。直接MF bouton Ca 2+成像显示，动作电位（AP）诱发的Ca 2+瞬变的Ca 2+衰减动力学较慢。最后，我们观察到异步释放优先由通过P / Q型电压门控Ca 2+通道的Ca 2+流入介导，而N型VGCC的贡献是有限的。总体而言，我们的研究结果揭示了从MF终端持续长时间异步释放的决定因素，并表明异步释放可能会在颗粒细胞爆发终止后的数秒内影响CA3锥体细胞的发射。
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