Impact of dendritic spine loss on excitability of hippocampal CA1 pyramidal neurons: a computational study of early Alzheimer disease.
Impact of dendritic spine loss on excitability of hippocampal CA1 pyramidal neurons: a computational study of early Alzheimer disease.
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树突棘损失对海马 CA1 锥体神经元兴奋性的影响：早期阿尔茨海默病的计算研究。
DOI：
10.1101/2024.01.20.576500
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Masurkar,ArjunV
中科院分区：
文献类型：
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作者：
Tian,Chengju;Reyes,Isabel;Masurkar,ArjunV
突触棘缺失是阿尔茨海默病（AD）的早期病理生理学标志，先于树突结构的明显缺失和明显的神经退行性变。虽然棘丢失意味着突触前靶点对突触后神经元的参与减少，但棘及其被动成分的丢失在多大程度上影响突触后神经元的兴奋性和对存活突触输入的反应尚不清楚。使用被动多房室模型的CA1锥体神经元（PN），牵连在早期AD，我们发现，脊柱损失单独驱动器的剩余输入到其近端和远端树突，分别由CA3和内嗅皮层（EC）为目标的提高。这种增强效应在远端树突比近端树突更高，并且可以通过限制于远端隔室的棘丢失来介导，足以影响突触输入整合和体树突反向传播。这与AD的非常早期阶段特别相关，其中病理生理学从EC延伸到CA 1。
Synaptic spine loss is an early pathophysiologic hallmark of Alzheimer disease (AD) that precedes overt loss of dendritic architecture and frank neurodegeneration. While spine loss signifies a decreased engagement of postsynaptic neurons by presynaptic targets, the degree to which loss of spines and their passive components impacts the excitability of postsynaptic neurons and responses to surviving synaptic inputs is unclear. Using passive multicompartmental models of CA1 pyramidal neurons (PNs), implicated in early AD, we find that spine loss alone drives a boosting of remaining inputs to their proximal and distal dendrites, targeted by CA3 and entorhinal cortex (EC), respectively. This boosting effect is higher in distal versus proximal dendrites and can be mediated by spine loss restricted to the distal compartment, enough to impact synaptic input integration and somatodendritic backpropagation. This has particular relevance to very early stages of AD in which pathophysiology extends from EC to CA1.