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首页> 外文期刊>Journal of Computational Neuroscience >Functional consequences of age-related morphologic changes to pyramidal neurons of the rhesus monkey prefrontal cortex
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Functional consequences of age-related morphologic changes to pyramidal neurons of the rhesus monkey prefrontal cortex

机译：年龄相关形态变化对恒河猴前额叶皮层锥体神经元的功能后果

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摘要

Layer 3 (L3) pyramidal neurons in the lateral prefrontal cortex (LPFC) of rhesus monkeys exhibit dendritic regression, spine loss and increased action potential (AP) firing rates during normal aging. The relationship between these structural and functional alterations, if any, is unknown. To address this issue, morphological and electrophysiological properties of L3 LPFC pyramidal neurons from young and aged rhesus monkeys were characterized using in vitro whole-cell patch-clamp recordings and high-resolution digital reconstruction of neurons. Consistent with our previous studies, aged neurons exhibited significantly reduced dendritic arbor length and spine density, as well as increased input resistance and firing rates. Computational models using the digital reconstructions with Hodgkin-Huxley and AMPA channels allowed us to assess relationships between demonstrated age-related changes and to predict physiological changes that have not yet been tested empirically. For example, the models predict that in both backpropagating APs and excitatory postsynaptic currents (EPSCs), attenuation is lower in aged versus young neurons. Importantly, when identical densities of passive parameters and voltage- and calcium-gated conductances were used in young and aged model neurons, neither input resistance nor firing rates differed between the two age groups. Tuning passive parameters for each model predicted significantly higher membrane resistance (R m ) in aged versus young neurons. This R m increase alone did not account for increased firing rates in aged models, but coupling these R m values with subtle differences in morphology and membrane capacitance did. The predicted differences in passive parameters (or parameters with similar effects) are mathematically plausible, but must be tested empirically.
机译：恒河猴的外侧前额叶皮层（LPFC）中的第3层（L3）锥体神经元在正常衰老期间表现出树突状退化，脊柱丢失和动作电位（AP）放电速率增加。这些结构和功能更改之间的关系（如果有的话）是未知的。为了解决这个问题，使用体外全细胞膜片钳记录和神经元的高分辨率数字重建来表征来自年轻和老年恒河猴的L3 LPFC锥体神经元的形态和电生理特性。与我们以前的研究一致，衰老的神经元显示出显着减少的树突状乔木长度和脊椎密度，以及增加的输入阻力和击发率。使用带有Hodgkin-Huxley和AMPA通道的数字重建的计算模型使我们能够评估已证明的与年龄相关的变化之间的关系，并预测尚未经过经验检验的生理变化。例如，这些模型预测，在反向传播的AP和兴奋性突触后电流（EPSC）中，衰老都比年轻的神经元低。重要的是，当在年轻和老年模型神经元中使用相同密度的被动参数以及电压门控和钙门控电导时，两个年龄组之间的输入电阻和放电率均无差异。调整每个模型的被动参数可预测，老年神经元与年轻神经元的膜抵抗力（R m）明显更高。仅Rm的增加并不能说明老化模型中点火率的增加，但是将这些Rm值与形态和膜电容的细微差别结合起来确实可以。被动参数（或具有相似效果的参数）的预测差异在数学上是合理的，但必须凭经验进行测试。

著录项

  • 来源
    《Journal of Computational Neuroscience》 |2015年第2期|263-283|共21页
  • 作者

    Patrick J. Coskren; Jennifer I. Luebke; Doron Kabaso; Susan L. Wearne; Aniruddha Yadav; Timothy Rumbell; Patrick R. Hof; Christina M. Weaver;

  • 作者单位

    Fishberg Department of Neuroscience and Friedman Brain Institute Icahn School of Medicine at Mount Sinai">(1);

    Computational Neurobiology and Imaging Center Icahn School of Medicine at Mount Sinai">(2);

    Computational Neurobiology and Imaging Center Icahn School of Medicine at Mount Sinai">(2);

    Department of Anatomy and Neurobiology Boston University School of Medicine">(3);

    Fishberg Department of Neuroscience and Friedman Brain Institute Icahn School of Medicine at Mount Sinai">(1);

    Computational Neurobiology and Imaging Center Icahn School of Medicine at Mount Sinai">(2);

    BARN-ICT Ltd">(5);

    Fishberg Department of Neuroscience and Friedman Brain Institute Icahn School of Medicine at Mount Sinai">(1);

    Computational Neurobiology and Imaging Center Icahn School of Medicine at Mount Sinai">(2);

    Fishberg Department of Neuroscience and Friedman Brain Institute Icahn School of Medicine at Mount Sinai">(1);

    Computational Neurobiology and Imaging Center Icahn School of Medicine at Mount Sinai">(2);

    Gauge Data Solutions Pvt Ltd">(6);

    Fishberg Department of Neuroscience and Friedman Brain Institute Icahn School of Medicine at Mount Sinai">(1);

    Computational Neurobiology and Imaging Center Icahn School of Medicine at Mount Sinai">(2);

    Fishberg Department of Neuroscience and Friedman Brain Institute Icahn School of Medicine at Mount Sinai">(1);

    Computational Neurobiology and Imaging Center Icahn School of Medicine at Mount Sinai">(2);

    Computational Neurobiology and Imaging Center Icahn School of Medicine at Mount Sinai">(2);

    Department of Mathematics and Computer Science Franklin and Marshall College">(4);

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  • 正文语种 eng
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  • 关键词

    Neuronal excitability; Dendrites; Spines; Morphology; Compartment model; Aging; Rhesus monkey; Passive parameters;

    机译：神经元兴奋性;树突;刺;形态学;车厢模型;老化;恒河猴;被动参数;

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