Dendritic branch structure compartmentalizes voltage-dependent calcium influx in cortical layer 2/3 pyramidal cells.
Dendritic branch structure compartmentalizes voltage-dependent calcium influx in cortical layer 2/3 pyramidal cells.
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DOI：
10.7554/elife.76993
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发表时间：
2022-03-23
期刊：
影响因子：
7.7
通讯作者：
Sabatini BL
中科院分区：
文献类型：
--
作者：
Landau AT;Park P;Wong-Campos JD;Tian H;Cohen AE;Sabatini BL
反向传播动作电位（bAPs）通过在树突中唤起电压依赖性钙内流来调节突触可塑性。远端树突腔室bAP振幅的衰减通过减少bAP依赖性钙内流以特定位置的方式改变可塑性。然而，目前尚不清楚神经元是否表现出bap依赖性钙信号的分支特异性变异性，而不依赖于距离依赖性衰减。在这里，我们揭示了bAPs不能通过小鼠皮质层2/3锥体细胞的特定树突状分支群体中的电压门控钙通道（vgcc）引起钙内流，尽管在姐妹分支中引起了大量vgcc介导的钙内流。这些分支包含vgc，并在没有突触输入的情况下成功地传播bap；然而，由于bAP振幅的分支特异性降低，它们没有表现出bAP诱发的钙内流。我们证明这些分支与姐妹分支相比具有更复杂的分支结构，这导致局部电紧张阻抗和bAP振幅的降低。最后，我们发现，由于VGCCs和nmda型谷氨酸受体的电压依赖性和动力学差异，bAPs仍然会放大这些分支中突触介导的钙内流。bap依赖性钙信号的分支特异性区隔化可能为神经元在树突树上多样化突触调节提供了一种机制。
Back-propagating action potentials (bAPs) regulate synaptic plasticity by evoking voltage-dependent calcium influx throughout dendrites. Attenuation of bAP amplitude in distal dendritic compartments alters plasticity in a location-specific manner by reducing bAP-dependent calcium influx. However, it is not known if neurons exhibit branch-specific variability in bAP-dependent calcium signals, independent of distance-dependent attenuation. Here, we reveal that bAPs fail to evoke calcium influx through voltage-gated calcium channels (VGCCs) in a specific population of dendritic branches in mouse cortical layer 2/3 pyramidal cells, despite evoking substantial VGCC-mediated calcium influx in sister branches. These branches contain VGCCs and successfully propagate bAPs in the absence of synaptic input; nevertheless, they fail to exhibit bAP-evoked calcium influx due to a branch-specific reduction in bAP amplitude. We demonstrate that these branches have more elaborate branch structure compared to sister branches, which causes a local reduction in electrotonic impedance and bAP amplitude. Finally, we show that bAPs still amplify synaptically-mediated calcium influx in these branches because of differences in the voltage-dependence and kinetics of VGCCs and NMDA-type glutamate receptors. Branch-specific compartmentalization of bAP-dependent calcium signals may provide a mechanism for neurons to diversify synaptic tuning across the dendritic tree.