Action potential counting at giant mossy fiber terminals gates information transfer in the hippocampus

Action potential counting at giant mossy fiber terminals gates information transfer in the hippocampus
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巨型苔藓纤维末端的动作电位计数控制了海马体的信息传递

DOI:
10.1101/158444
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发表时间:
2017
期刊:
--
影响因子:
--
通讯作者:
Chamberland S
Chamberland S
中科院分区:
--
文献类型:
--
作者:
Chamberland S

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神经元的通信依赖于动作电位的放电,动作电位编码信息的频率和时间精度。长期以来,海马苔藓纤维一直被认为是条件引爆器,因为在颗粒细胞爆裂放电过程中显示出显著的短期促进谷氨酸释放的作用。然而,触发CA3锥体神经元动作电位放电所需的尖峰模式仍然知之甚少。在这里,我们证明了从苔藓纤维终末释放谷氨酸触发了靶CA3锥体神经元的动作电位激发,而不依赖于颗粒细胞的平均爆发频率,这种现象我们称之为动作电位计数。我们发现苔藓纤维中的动作电位计数门谷氨酸在广泛的生理频率和动作电位数范围内释放。利用快速的钙离子成像,我们还发现,在动作电位序列中,诱发的钙离子内流的幅度保持不变,而累积的剩余钙离子在几百毫秒的时间尺度上逐渐被挤出。使用实验受限的突触前钙离子内流、缓冲和扩散的三维模型,以及钙离子激活的囊泡融合的蒙特卡罗模型,我们认为苔藓纤维周围的动作电位计数可以用钙离子动力学和释放部位缓冲之间的独特相互作用来解释。这在很大程度上是由主要的内源性钙缓冲剂Calbindin-D28K和CaM的不同贡献决定的,也是由突触前电压门控钙通道和释放感受器之间的松散耦合以及相对较慢的钙挤出速率决定的。综上所述,我们的结果确定了大脑中一种以前未被探索的信息编码机制。
Neuronal communication relies on action potential discharge, with the frequency and the temporal precision of action potentials encoding information. Hippocampal mossy fibers have long been recognized as conditional detonators owing to prominent short-term facilitation of glutamate release displayed during granule cell burst firing. However, the spiking patterns required to trigger action potential firing in CA3 pyramidal neurons remain poorly understood. Here, we show that glutamate release from mossy fiber terminals triggers action potential firing of the target CA3 pyramidal neurons independently of the average granule cell burst frequency, a phenomenon we term action potential counting. We find that action potential counting in mossy fibers gates glutamate release over a broad physiological range of frequencies and action potential numbers. Using rapid Ca2+imaging we also show that the magnitude of evoked Ca2+influx stays constant during action potential trains and that accumulated residual Ca2+is gradually extruded on a time scale of several hundred milliseconds. Using experimentally constrained 3D model of presynaptic Ca2+influx, buffering, and diffusion, and a Monte Carlo model of Ca2+-activated vesicle fusion, we argue that action potential counting at mossy fiber boutons can be explained by a unique interplay between Ca2+dynamics and buffering at release sites. This is largely determined by the differential contribution of major endogenous Ca2+buffers calbindin-D28Kand calmodulin and by the loose coupling between presynaptic voltage-gated Ca2+channels and release sensors and the relatively slow Ca2+extrusion rate. Taken together, our results identify a previously unexplored information-coding mechanism in the brain.
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