Computer Simulations Support a Morphological Contribution to BDNF Enhancement of Action Potential Generation.

Computer Simulations Support a Morphological Contribution to BDNF Enhancement of Action Potential Generation.
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DOI:
10.3389/fncel.2016.00209
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发表时间:
2016
影响因子:
5.3
通讯作者:
Jones KR
Jones KR
中科院分区:
医学2区
文献类型:
--
作者:
Galati DF;Hiester BG;Jones KR

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脑源性神经营养因子 (BDNF) 调节动作电位 (AP) 的产生和神经元形态。然而,BDNF 诱导的神经元形态变化是否直接影响 AP 的生成尚不清楚。我们量化了 BDNF 对培养的皮质神经元形态参数的影响,发现 BDNF 刺激树突生长和树突添加,同时以空间限制的方式增加兴奋性和抑制性突触前输入。为了深入了解神经元结构和突触输入的这些组合变化如何影响 AP 的生成,我们使用收集的形态参数来生成计算模型。模拟表明 BDNF 诱导的神经元形态在各种条件下都会产生更多的 AP。突触和树突的添加对 AP 的生成影响最大。然而,当突触活性较低时,兴奋性/抑制性突触比率和强度的细微变化会对 AP 的生成产生重大影响。与这些模拟一致,BDNF 迅速增强皮质培养物中的自发活动。我们认为 BDNF 促进神经元形态本质上更有效地将大量突触活动转化为 AP,这是 BDNF 功能之前未探索的方面。
Brain-derived neurotrophic factor (BDNF) regulates both action potential (AP) generation and neuron morphology. However, whether BDNF-induced changes in neuron morphology directly impact AP generation is unclear. We quantified BDNF’s effect on cultured cortical neuron morphological parameters and found that BDNF stimulates dendrite growth and addition of dendrites while increasing both excitatory and inhibitory presynaptic inputs in a spatially restricted manner. To gain insight into how these combined changes in neuron structure and synaptic input impact AP generation, we used the morphological parameters we gathered to generate computational models. Simulations suggest that BDNF-induced neuron morphologies generate more APs under a wide variety of conditions. Synapse and dendrite addition have the greatest impact on AP generation. However, subtle alterations in excitatory/inhibitory synapse ratio and strength have a significant impact on AP generation when synaptic activity is low. Consistent with these simulations, BDNF rapidly enhances spontaneous activity in cortical cultures. We propose that BDNF promotes neuron morphologies that are intrinsically more efficient at translating barrages of synaptic activity into APs, which is a previously unexplored aspect of BDNF’s function.
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