Dendritic distributions of I h channels in experimentally-derived multi-compartment models of oriens-lacunosum/moleculare (O-LM) hippocampal interneurons.
Dendritic distributions of I h channels in experimentally-derived multi-compartment models of oriens-lacunosum/moleculare (O-LM) hippocampal interneurons.
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DOI：
10.3389/fnsyn.2015.00002
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发表时间：
2015
影响因子：
3.7
通讯作者：
Skinner FK
中科院分区：
文献类型：
--
作者：
Sekulić V;Chen TC;Lawrence JJ;Skinner FK
O-LM细胞类型介导对海马锥体细胞的反馈抑制，并控制CA 1中的信息流。其功能依赖于电压门控通道（VGC）的存在，这影响其整合特性和对突触输入的反应。鉴于确定中间神经元树突上VGC的密度和分布相关的挑战，我们利用计算建模来考虑不同的可能性。在这项工作中，我们专注于超极化激活通道（h通道）在O-LM细胞。虽然已知h通道存在于O-LM细胞中，但尚不清楚它们是否存在于树突上。在以前的工作中，我们使用集成建模技术与实验数据，以获得潜在的重要电导平衡的见解。我们发现，最好的O-LM模型，包括均匀分布的h-通道的树突不能完全捕获的“下垂”的响应。这使我们在目前的工作中检查h通道的激活动力学和非均匀分布。在调整我们的模型，我们发现，不同的动力学和非均匀分布可以更好地再现实验O-LM细胞的反应。相反，CA 1锥体细胞的H-通道更高的电导密度发生在更远的树突，降低电导密度的H-通道远离索马在O-LM模型中观察到。通过一个说明性的方案，我们表明，树突状h-通道明显加快反向传播的动作电位在O-LM细胞，不像h-通道只存在于索马。虽然目前的结果是依赖于形态，我们的工作表明，它应该是可能的，以确定的分布和特征的O-LM细胞的记录和形态从同一个细胞。我们假设h-通道分布在O-LM细胞树突中，并赋予它们特定的突触整合特性，从而塑造海马中的信息流。
The O-LM cell type mediates feedback inhibition onto hippocampal pyramidal cells and gates information flow in the CA1. Its functions depend on the presence of voltage-gated channels (VGCs), which affect its integrative properties and response to synaptic input. Given the challenges associated with determining densities and distributions of VGCs on interneuron dendrites, we take advantage of computational modeling to consider different possibilities. In this work, we focus on hyperpolarization-activated channels (h-channels) in O-LM cells. While h-channels are known to be present in O-LM cells, it is unknown whether they are present on their dendrites. In previous work, we used ensemble modeling techniques with experimental data to obtain insights into potentially important conductance balances. We found that the best O-LM models that included uniformly distributed h-channels in the dendrites could not fully capture the “sag” response. This led us to examine activation kinetics and non-uniform distributions of h-channels in the present work. In tuning our models, we found that different kinetics and non-uniform distributions could better reproduce experimental O-LM cell responses. In contrast to CA1 pyramidal cells where higher conductance densities of h-channels occur in more distal dendrites, decreasing conductance densities of h-channels away from the soma were observed in O-LM models. Via an illustrative scenario, we showed that having dendritic h-channels clearly speeds up back-propagating action potentials in O-LM cells, unlike when h-channels are present only in the soma. Although the present results were morphology-dependent, our work shows that it should be possible to determine the distributions and characteristics of O-LM cells with recordings and morphologies from the same cell. We hypothesize that h-channels are distributed in O-LM cell dendrites and endow them with particular synaptic integration properties that shape information flow in hippocampus.