Heightened cortical excitability in aged rodents with memory impairment.
Heightened cortical excitability in aged rodents with memory impairment.
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DOI：
10.1016/j.neurobiolaging.2016.12.021
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发表时间：
2017-06
影响因子：
4.2
通讯作者：
Gallagher M
中科院分区：
文献类型：
--
作者：
Haberman RP;Koh MT;Gallagher M
海马区兴奋性升高已成为老年性记忆功能减退和阿尔茨海默病前驱症状认知障碍的关键因素。在这里，我们使用记忆障碍的个体差异的老年大鼠模型，研究了海马区和连接皮质网络中神经活动和记忆之间的关系。CFO的表达被用来衡量药物诱导的神经活动。老年记忆受损大鼠在海马区CA3亚区以及包括脾后皮质、顶叶皮质和眶前皮质在内的几个皮质区域的CFO比年轻成年大鼠和老年未受损大鼠高。激活网络中CFO强度与任务绩效之间的强相关性表明，在衰老过程中，兴奋性与认知表型之间存在紧密耦合。左乙拉西坦的治疗降低了从海马体延伸到相互连接的后脑皮质(脾后/顶叶)的神经兴奋性升高，左乙拉西坦是一种具有行为功效的治疗药物，以前已从与年龄相关的损害和阿尔茨海默病的啮齿动物模型移植到患有遗忘性轻度认知障碍的人类。
Elevated excitability in the hippocampus has emerged as a key contributor to reduced memory function in aging and in cognitive impairment prodromal to Alzheimer’s disease. Here, we investigated the relationship between neural activity and memory in the hippocampus and a connectional cortical network using an aged rat model of individual differences for memory impairment. The expression of cFos was used as a measure of pharmacologically induced neural activity. Aged memory-impaired rats exhibited elevated cFos relative to young adult and aged unimpaired rats in the CA3 subfield of the hippocampus and in several cortical regions including the retrosplenial, parietal, and orbitofrontal cortices. Strong correlations between cFos intensity and task performance across the activated network showed a tight coupling between excitability and cognitive phenotype in aging. Elevated neural excitability extending beyond the hippocampus to interconnected posterior cortex (retrosplenial/parietal) was reduced by treatment with levetiracetam, a therapeutic with behavioral efficacy that has previously translated from rodent models of age-related impairment and Alzheimer’s disease to humans with amnestic mild cognitive impairment.