Recruitment of an inhibitory hippocampal network after bursting in a single granule cell
Recruitment of an inhibitory hippocampal network after bursting in a single granule cell
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DOI：
10.1073/pnas.0702164104
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发表时间：
2007-05-01
影响因子：
11.1
通讯作者：
Gerber, Urs
中科院分区：
文献类型：
--
作者：
Mori, Masahiro;Gahwiler, Beat H.;Gerber, Urs
海马CA3区是一个与记忆功能有关的联想网络，通过齿状颗粒细胞的苔藓纤维轴突接受单突触兴奋性和双突触抑制性输入。由苔藓纤维制成的突触释放概率低，导致在0.1赫兹的静息放电频率下失败率高。在功能相连的神经元对的记录中，颗粒细胞的突然放电增加了谷氨酸释放到CA3锥体细胞和抑制性中间神经元的可能性，因此随后的低频刺激在CA3锥体细胞中引发双相兴奋/抑制反应，这种效应持续数分钟。对回路中单一连接的分析表明，颗粒细胞的破裂导致了抑制网络的强大激活，从而瞬时抑制了对CA3锥体细胞的兴奋性输入。这一现象反映了颗粒细胞到神经元间突触的棘波-棘波传递的高发生率，抑制性中间神经元的苔藓纤维比主细胞在数量上更多的靶向，以及针对CA3锥体细胞的中间神经元的广泛分化的输出。因此，苔藓纤维输入到CA3锥体细胞似乎有三种不同的模式：静息模式，由于失败率高，突触传递无效；爆发模式，兴奋占主导地位；以及爆发后模式，对CA3锥体细胞的抑制输入大大增强。一种允许抑制输入的瞬时招募的机制对于控制高度相互连接的CA3锥体细胞区的网络活动可能是重要的。
The hippocampal CA3 area, an associational network implicated in memory function, receives monosynaptic excitatory as well as disynaptic inhibitory input through the mossy-fiber axons of the dentate granule cells. Synapses made by mossy fibers exhibit low release probability, resulting in high failure rates at resting discharge frequencies of 0.1 Hz. In recordings from functionally connected pairs of neurons, burst firing of a granule cell increased the probability of glutamate release onto both CA3 pyramidal cells and inhibitory interneurons, such that subsequent low-frequency stimulation evoked biphasic excitatory/inhibitory responses in a CA3 pyramidal cell, an effect lasting for minutes. Analysis of the unitary connections in the circuit revealed that granule cell bursting caused powerful activation of an inhibitory network, thereby transiently suppressing excitatory input to CA3 pyramidal cells. This phenomenon reflects the high incidence of spike-to-spike transmission at granule cell to interneuron synapses, the numerically much greater targeting by mossy fibers of inhibitory interneurons versus principal cells, and the extensively divergent output of interneurons targeting CA3 pyramidal cells. Thus, mossy-fiber input to CA3 pyramidal cells appears to function in three distinct modes: a resting mode, in which synaptic transmission is ineffectual because of high failure rates; a bursting mode, in which excitation predominates; and a postbursting mode, in which inhibitory input to the CA3 pyramidal cells is greatly enhanced. A mechanism allowing the transient recruitment of inhibitory input may be important for controlling network activity in the highly interconnected CA3 pyramidal cell region.