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在海马中的信息传递。
DOI：
10.1073/pnas.1720659115
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发表时间：
2018-07-10
影响因子：
11.1
通讯作者：
Tóth K
中科院分区：
文献类型：
--
作者：
Chamberland S;Timofeeva Y;Evstratova A;Volynski K;Tóth K
神经元发射动作电位，通过突触释放神经递质传递信息。在突触前末端，动作电位放电模式通过动态Ca2+信号被突触前机制整合，触发神经递质释放。一般认为，动作电位放电的频率和时间精度支持神经元间的信息传递。在这里，我们发现与速率和时间编码相反，巨大的苔藓纤维终端在触发CA3锥体细胞放电的过程中计数动作电位的数量。我们的研究结果揭示了突触信号传递机制，支持大脑中额外的信息编码策略。神经元间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决定了神经元间的通信。海马苔藓纤维长期以来被认为是条件雷管，因为它在颗粒细胞爆发过程中表现出显著的短期谷氨酸释放促进作用。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，我们发现从苔藓纤维末端释放谷氨酸会触发目标CA3锥体神经元的动作电位放电，而不依赖于平均颗粒细胞爆发频率，我们将这种现象称为动作电位计数。我们发现苔藓纤维中的动作电位计数在广泛的生理频率和动作电位数范围内控制谷氨酸释放。利用快速Ca2+成像，我们还表明，在动作电位训练期间，诱发Ca2+内流的幅度保持不变，积累的残余Ca2+在几百毫秒的时间尺度上逐渐挤出。利用实验约束的突触前Ca2+内流、缓冲和扩散的3D模型，以及Ca2+激活囊泡融合的蒙特卡罗模型，我们认为苔藓纤维钮扣的动作电位计数可以通过Ca2+动力学和释放位点缓冲之间的独特相互作用来解释。这在很大程度上取决于主要内源性Ca2+缓冲剂calbinin - d28k和calmodulin的差异贡献，以及突触前电压门控Ca2+通道和释放传感器之间的松散耦合以及相对缓慢的Ca2+挤压速率。综上所述，我们的研究结果确定了大脑中一个以前未被探索的信息编码机制。
Neurons fire action potentials to transfer information through synaptic release of neurotransmitter. At presynaptic terminals, the pattern of action potential discharge is integrated through dynamic Ca2+ signaling by the presynaptic machinery which triggers the release of neurotransmitter. It is generally accepted that the rate and the temporal precision of action potential firing support information transfer between neurons. Here, we show that in contrast to rate and temporal coding, giant mossy fiber terminals count the number of action potentials during trains to trigger CA3 pyramidal cell firing. Our results shed light on the synaptic signal transfer mechanisms supporting an additional information coding strategy in the brain. 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-D28K and 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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影响因子：
25
作者：
Henze, DA;Wittner, L;Buzsáki, G
通讯作者：
Buzsáki, G
影响因子：
2.5
作者：
AMARAL, DG;DENT, JA
通讯作者：
DENT, JA
影响因子：
16.2
作者：
Pelkey, Kenneth A.;Topolnik, Lisa;McBain, Chris J.
通讯作者：
McBain, Chris J.
影响因子：
16.2
作者：
Geiger, JRP;Jonas, P
通讯作者：
Jonas, P
影响因子：
25
作者：
Ermolyuk, Yaroslav S.;Alder, Felicity G.;Surges, Rainer;Pavlov, Ivan Y.;Timofeeva, Yulia;Kullmann, Dimitri M.;Volynski, Kirill E.
通讯作者：
Volynski, Kirill E.