Mild traumatic brain injury (mTBI) presents a significant health concern with potential persisting deficits that can last decades. Although a growing body of literature improves our understanding of the brain network response and corresponding underlying cellular alterations after injury, the effects of cellular disruptions on local circuitry after mTBI are poorly understood. Our group recently reported how mTBI in neuronal networks affects the functional wiring of neural circuits and how neuronal inactivation influences the synchrony of coupled microcircuits. Here, we utilized a computational neural network model to investigate the circuit-level effects of N-methyl D-aspartate receptor dysfunction. The initial increase in activity in injured neurons spreads to downstream neurons, but this increase was partially reduced by restructuring the network with spike-timing-dependent plasticity. As a model of network-based learning, we also investigated how injury alters pattern acquisition, recall, and maintenance of a conditioned response to stimulus. Although pattern acquisition and maintenance were impaired in injured networks, the greatest deficits arose in recall of previously trained patterns. These results demonstrate how one specific mechanism of cellular-level damage in mTBI affects the overall function of a neural network and point to the importance of reversing cellular-level changes to recover important properties of learning and memory in a microcircuit.

中文翻译：

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轻度创伤性脑损伤后 NMDA 受体的改变导致记忆获取和回忆缺陷

轻度创伤性脑损伤 (mTBI) 是一个重要的健康问题，潜在的持续缺陷可能会持续数十年。尽管越来越多的文献提高了我们对损伤后脑网络反应和相应的潜在细胞改变的理解，但对 mTBI 后细胞破坏对局部回路的影响知之甚少。我们小组最近报道了神经元网络中的 mTBI 如何影响神经回路的功能布线以及神经元失活如何影响耦合微回路的同步。在这里，我们利用计算神经网络模型来研究 N-甲基 D-天冬氨酸受体功能障碍的电路级影响。受损神经元活动的最初增加会扩散到下游神经元，但是这种增加通过重组具有尖峰时间依赖性可塑性的网络而部分减少。作为基于网络的学习模型，我们还研究了损伤如何改变对刺激的条件反应的模式获取、回忆和维持。尽管在受伤的网络中模式获取和维护受到损害，但最大的缺陷出现在对先前训练模式的回忆中。这些结果证明了 mTBI 中细胞水平损伤的一种特定机制如何影响神经网络的整体功能，并指出逆转细胞水平变化以恢复微电路中学习和记忆的重要特性的重要性。并维持对刺激的条件反应。尽管在受伤的网络中模式获取和维护受到损害，但最大的缺陷出现在对先前训练模式的回忆中。这些结果证明了 mTBI 中细胞水平损伤的一种特定机制如何影响神经网络的整体功能，并指出逆转细胞水平变化以恢复微电路中学习和记忆的重要特性的重要性。并维持对刺激的条件反应。尽管在受伤的网络中模式获取和维护受到损害，但最大的缺陷出现在对先前训练模式的回忆中。这些结果证明了 mTBI 中细胞水平损伤的一种特定机制如何影响神经网络的整体功能，并指出逆转细胞水平变化以恢复微电路中学习和记忆的重要特性的重要性。