Imbalanced pattern completion vs. separation in cognitive disease: network simulations of synaptic pathologies predict a personalized therapeutics strategy
Imbalanced pattern completion vs. separation in cognitive disease: network simulations of synaptic pathologies predict a personalized therapeutics strategy
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DOI：
10.1186/1471-2202-11-96
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发表时间：
2010-08-13
期刊：
影响因子：
2.4
通讯作者：
Madison, Daniel V.
中科院分区：
文献类型：
--
作者：
Hanson, Jesse E.;Madison, Daniel V.
背景资料：认知受损的神经发育、神经精神和神经变性原因的多种小鼠遗传模型表现出至少四个突触功能障碍的会聚点：1）长时程增强（LTP）的强度，2）长时程抑制（LTD）的强度，3）相对抑制水平。（抑制）和4）兴奋性连接水平（连接性）。为了验证这一假设，即这些突触特性的病理性增加或减少可能是基本神经网络功能水平不平衡的基础，我们在自联想记忆的模拟中探索了每种类型的故障。这些网络模拟显示，这些突触特性中的每一个的损伤或过度的一个影响是在记忆存储和回忆期间改变模式分离和模式完成性能之间的权衡。每种突触病理都将网络平衡推向模式分离中不可容忍的错误或模式完成中不可容忍的错误。由LTP、LTD、抑制或连接的病理性损伤或过度引起的不平衡，都可以通过同时调节其他三种突触特性中的任何一种来加剧或挽救。因为对任何突触特性的适当调节都有助于重新平衡网络功能，而不管失衡的根源是什么，我们提出了一种新的策略，个性化的认知治疗引导模式完成与模式分离功能的分析。模拟的例子和可测试的预测，这种理论化的认知治疗方法。
Background: Diverse Mouse genetic models of neurodevelopmental, neuropsychiatric, and neurodegenerative causes of impaired cognition exhibit at least four convergent points of synaptic malfunction: 1) Strength of long-term potentiation (LTP), 2) Strength of long-term depression (LTD), 3) Relative inhibition levels (Inhibition), and 4) Excitatory connectivity levels (Connectivity).Results: To test the hypothesis that pathological increases or decreases in these synaptic properties could underlie imbalances at the level of basic neural network function, we explored each type of malfunction in a simulation of autoassociative memory. These network simulations revealed that one impact of impairments or excesses in each of these synaptic properties is to shift the trade-off between pattern separation and pattern completion performance during memory storage and recall. Each type of synaptic pathology either pushed the network balance towards intolerable error in pattern separation or intolerable error in pattern completion. Imbalances caused by pathological impairments or excesses in LTP, LTD, inhibition, or connectivity, could all be exacerbated, or rescued, by the simultaneous modulation of any of the other three synaptic properties.Conclusions: Because appropriate modulation of any of the synaptic properties could help re-balance network function, regardless of the origins of the imbalance, we propose a new strategy of personalized cognitive therapeutics guided by assay of pattern completion vs. pattern separation function. Simulated examples and testable predictions of this theorized approach to cognitive therapeutics are presented.