A model of a CA3 hippocampal pyramidal neuron incorporating voltage-clamp data on intrinsic conductances.
A model of a CA3 hippocampal pyramidal neuron incorporating voltage-clamp data on intrinsic conductances.
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DOI：
10.1152/jn.1991.66.2.635
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发表时间：
1991-08
影响因子：
2.5
通讯作者：
R. Traub;R. Wong;R. Miles;H. Michelson
中科院分区：
文献类型：
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作者：
R. Traub;R. Wong;R. Miles;H. Michelson
1.建立了豚鼠CA3区锥体神经元19室缆索模型。每个隔室允许包含六个活性离子导体：GNA、GCA、GK(DR)(其中DR代表延迟整流)、GK(A)、GK(AHP)和GK(C)。电导GCA为高压激励型。前五种电导的模型动力学结合了从分离的海马锥体神经元获得的电压钳数据。GK(C)的动力学是基于牛蛙交感神经元的数据。膜下钙衰变的时间常数来自浦肯野细胞树突中钙信号的光学成像。2.为了从现有的电压钳数据构建模型，我们首先复制了一个模型分离神经元(胞体加近端树突)的电流钳记录。接下来，我们假设树突中的离子通道动力学与胞体中的相同。根据树突记录和钙成像数据，我们还假设在树突中存在显著的GCA。然后，我们连接了部分基底和根尖树突索。通过反复试验，我们发现了一种离子电导密度的分布(不一定是唯一的)，这与来自整个神经元的胞体和树突以及孤立的顶树突的电流钳记录一致。3.所建立的模型再现了在一个刺激亚阈值后记录的依赖于钙离子的去极化后电位(DAP)。4.该模型还再现了注入不断增加的体细胞去极化电流的CA3区锥体神经元的行为：小电流的低频(0.3-1.0赫兹)节律性爆发，爆发频率随着电流大小的增加而增加；然后是更多的不规则爆发，随后是后超极化(AHP)，并夹杂着短暂的爆发，而不是AHP；最后，没有爆发的节律性动作电位。5.该模型预测在紧张性去极化树突刺激过程中还存在另一种放电模式：在小于1至大约12赫兹的短暂爆发，这种模式在躯体刺激中没有观察到。这些爆发与有节奏的树枝状钙峰相对应。6.通过增加Gk(DR)，降低树突GCA和Gk(C)，可以使CA3模型锥体神经元在功能上类似于CA1锥体神经元。具体地说，在这些改变之后，胞体的强直去极化导致适应重复放电，而刺激远端树突则导致爆裂。7.一组关键参数涉及与膜通道(gk(C)和gk(AHP))相互作用的细胞内[Ca~(2+)]池的调节，特别是在树突中。
1. We have developed a 19-compartment cable model of a guinea pig CA3 pyramidal neuron. Each compartment is allowed to contain six active ionic conductances: gNa, gCa, gK(DR) (where DR stands for delayed rectifier), gK(A), gK(AHP), and gK(C). THe conductance gCa is of the high-voltage activated type. The model kinetics for the first five of these conductances incorporate voltage-clamp data obtained from isolated hippocampal pyramidal neurons. The kinetics of gK(C) are based on data from bullfrog sympathetic neurons. The time constant for decay of submembrane calcium derives from optical imaging of Ca signals in Purkinje cell dendrites. 2. To construct the model from available voltage-clamp data, we first reproduced current-clamp records from a model isolated neuron (soma plus proximal dendrites). We next assumed that ionic channel kinetics in the dendrites were the same as in the soma. In accord with dendritic recordings and calcium-imaging data, we also assumed that significant gCa occurs in dendrites. We then attached sections of basilar and apical dendritic cable. By trial and error, we found a distribution (not necessarily unique) of ionic conductance densities that was consistent with current-clamp records from the soma and dendrites of whole neurons and from isolated apical dendrites. 3. The resulting model reproduces the Ca(2+)-dependent spike depolarizing afterpotential (DAP) recorded after a stimulus subthreshold for burst elicitation. 4. The model also reproduces the behavior of CA3 pyramidal neurons injected with increasing somatic depolarizing currents: low-frequency (0.3-1.0 Hz) rhythmic bursting for small currents, with burst frequency increasing with current magnitude; then more irregular bursts followed by afterhyperpolarizations (AHPs) interspersed with brief bursts without AHPs; and finally, rhythmic action potentials without bursts. 5. The model predicts the existence of still another firing pattern during tonic depolarizing dendritic stimulation: brief bursts at less than 1 to approximately 12 Hz, a pattern not observed during somatic stimulation. These bursts correspond to rhythmic dendritic calcium spikes. 6. The model CA3 pyramidal neuron can be made to resemble functionally a CA1 pyramidal neuron by increasing gK(DR) and decreasing dendritic gCa and gK(C). Specifically, after these alterations, tonic depolarization of the soma leads to adapting repetitive firing, whereas stimulation of the distal dendrites leads to bursting. 7. A critical set of parameters concerns the regulation of the pool of intracellular [Ca2+] that interacts with membrane channels (gK(C) and gK(AHP)), particularly in the dendrites.(ABSTRACT TRUNCATED AT 400 WORDS)