"Disruption of neuronal circuitry and the memory engram in young adult mice following neonatal hypoxic-ischemic injury:

项目总结 新生儿缺氧缺血性脑病(HIE)后的认知和行为结局 在新生儿期进行预测。先前的研究已经证实，新生儿的MRI和神经学检查 对于行为和认知缺陷，时期是糟糕的预测工具。工作记忆和空间记忆缺陷 存在于暴露于新生缺氧缺血的幼年成年小鼠中。考察一家久负盛名的 利用新方法建立新生小鼠缺氧缺血性脑损伤模型，我们的初步数据发现 一组年轻的成年小鼠表现出发作间期棘波和慢性异常神经元激活。 海马区-海马区旁回路。记忆印记的概念涉及到这个电路和一个特定的 记忆是编码的，储存在特定的神经元群体中。因此，我们提出记忆印记 被发作间期棘波和慢性异常的海马神经元活动所干扰 与新生儿缺氧缺血性脑病相关的回路。首先，我们将表征脑电异常和神经元活动。 用神经元激活法研究新生小鼠缺氧缺血后的海马环路 在脂质清除的转基因小鼠大脑和高质量的脑电记录中进行定位。我们会调查的 脑电异常、海马神经元活动异常与脑电中断之间的联系 在这个模型中的记忆印记。

PROJECT SUMMARY Cognitive and behavioral outcomes following neonatal hypoxic-ischemic encephalopathy (HIE) are difficult to predict during the neonatal period. Previous work has established that MRI and neurologic exam in the neonatal period are poor prognostic tools for behavioral and cognitive deficits. Deficits in working and spatial memory exist in young adult mice that were exposed to neonatal hypoxia-ischemia. Examining a well-established neonatal mouse model of hypoxic-ischemic brain injury using novel methods, our preliminary data has found that a subset of young adult mice exhibit interictal spikes and chronic abnormal neuronal activation in the hippocampal-parahippocampal circuit. The concept of a memory engram involves this circuit and that a specific memory is encoded is stored in a specific population of neurons. Therefore, we propose that the memory engram is disrupted by interictal spikes and chronically abnormal neuronal activity in the hippocampal-parahippocampal circuit related to neonatal HIE. First, we will characterize electrographic abnormalities and neuronal activity in the hippocampal circuitry in young adult mice following neonatal hypoxia-ischemia using neuronal activation mapping in lipid cleared transgenic mouse brains and high quality electrographic recordings. We will investigate the link between electrographic abnormalities, abnormal neuronal activity in hippocampal circuitry and disruption of the memory engram in this model.