Altered synaptic and non-synaptic properties of CA1 pyramidal neurons in Kv4.2 knockout mice
Altered synaptic and non-synaptic properties of CA1 pyramidal neurons in Kv4.2 knockout mice
复制标题
DOI：
10.1113/jphysiol.2008.154336
复制
发表时间：
2008-08-15
影响因子：
5.5
通讯作者：
Magee, J. C.
中科院分区：
文献类型：
--
作者：
Andrasfalvy, B. K.;Makara, J. K.;Magee, J. C.
从神经元的索马到树突的反向传播动作电位（Back-propagating action potential，bAP）参与突触可塑性的各个方面。Kv 4.2介导的A型钾电流沿着CA 1锥体细胞（CA 1 PC）顶树突的距离依赖性增加是bAP振幅随距离索马而衰减的原因。Kv4.2基因的缺失降低了树突A型K（+）电流，增加了远端树突的bAP振幅。我们以前的研究表明，单一的Schaffer侧支输入的幅度增加与索马沿着顶树突的CA 1 PC的距离。我们测试的假设，远端突触的重量取决于树突Kv4.2通道。我们比较了野生型（WT）和Kv4.2基因敲除（KO）小鼠CA 1 PC主要顶干上不同位置的mEPSC的幅度和动力学。虽然野生型小鼠显示出正常的距离依赖性缩放，但在Kv4.2 KO小鼠中却缺失。我们还测试了在Kv4.2敲除中是否存在抑制的增加，其是为了补偿神经元兴奋性的非特异性增加而诱导的（在KO中后极化持续时间和爆发放电概率增加）。事实上，我们发现，在Kv4.2 KO小鼠中，紧张性GABA电流的幅度增加了53%，mIPSC的幅度增加了25%，如在索马处所记录的。我们的研究结果表明，树突状细胞的K（+）通道在突触强度的距离依赖性调节中的重要作用，以及紧张性抑制在调节整体突触强度和膜兴奋性的主要作用。
Back-propagating action potentials (bAPs) travelling from the soma to the dendrites of neurons are involved in various aspects of synaptic plasticity. The distance-dependent increase in Kv4.2-mediated A-type K(+) current along the apical dendrites of CA1 pyramidal cells (CA1 PCs) is responsible for the attenuation of bAP amplitude with distance from the soma. Genetic deletion of Kv4.2 reduced dendritic A-type K(+) current and increased the bAP amplitude in distal dendrites. Our previous studies revealed that the amplitude of unitary Schaffer collateral inputs increases with distance from the soma along the apical dendrites of CA1 PCs. We tested the hypothesis that the weight of distal synapses is dependent on dendritic Kv4.2 channels. We compared the amplitude and kinetics of mEPSCs at different locations on the main apical trunk of CA1 PCs from wild-type (WT) and Kv4.2 knockout (KO) mice. While wild-type mice showed normal distance-dependent scaling, it was missing in the Kv4.2 KO mice. We also tested whether there was an increase in inhibition in the Kv4.2 knockout, induced in an attempt to compensate for a non-specific increase in neuronal excitability (after-polarization duration and burst firing probability were increased in KO). Indeed, we found that the magnitude of the tonic GABA current increased in Kv4.2 KO mice by 53% and the amplitude of mIPSCs increased by 25%, as recorded at the soma. Our results suggest important roles for the dendritic K(+) channels in distance-dependent adjustment of synaptic strength as well as a primary role for tonic inhibition in the regulation of global synaptic strength and membrane excitability.