Synaptic Alterations in the Cerebral Cortex during Aging

描述（由申请方提供）：人类的衰老过程导致高级CNS功能退化。大脑皮层神经元及其突触所经历的与认知功能相关的变化是在老年观察到的这些认知缺陷的核心。然而，缺乏实验数据来确定哪些新皮层神经元和哪些突触在结构上或功能上受到最大的影响，以及在哪个时间序列中受到影响。本项目将验证以下假设：1）大型锥体神经元比非锥体皮质神经元对衰老过程更敏感，以及2）认知受损的老年人新皮质中可能存在锥体神经元兴奋性和抑制性影响之间的不平衡。为了验证上述假设，一个多学科的团队将应用行为，生理和心理的组合。（单细胞电生理学，膜片钳）和形态学（细胞内标记神经元的光学和电子显微镜免疫细胞化学）研究来确定哪些特定的大脑皮层神经元最受衰老的影响，它们的突触模式是什么，以及当与老年非受损动物相比时，在记忆受损的老年动物中是否发生兴奋性和抑制性突触放电之间的不平衡。这项研究应该揭示哪些神经元和递质特异性突触系统更容易受到衰老过程的影响，从而为它们的保护和/或纠正药物治疗提供有价值的线索。

DESCRIPTION (provided by applicant): The aging process in the human species leads to the deterioration of higher CNS functions. Age-related changes experienced by cerebral cortex neurons and their synapses are at the heart of these cognitive deficiencies observed in the old age. There is, however, scanty experimental data defining which neocortical neurons and which synapses are most affected structurally or functionally and in which temporal sequence. This project will test the hypothesis that 1) large pyramidal neurons are more sensitive than non-pyramidal cortical neurons to the aging process and that 2) an imbalance between excitatory and inhibitory influences upon pyramidal neurons might exist in the neocortex of cognitively impaired aged individuals. To test the above hypotheses a multidisciplinary team will apply a combination of behavioral, physiological (single cell electrophysiological, patch clamp) and morphological (light and electron microscopy immunocytochemistry of intracellularly labeled neurons) studies to define which particular cerebral cortex neurons are most affected with aging, what is their synaptic pattern and whether an imbalance between excitatory and inhibitory synaptic discharges occur in memory impaired aged animals when compared with aged non-impaired animals. This research should reveal which neuronal and transmitter-specific synaptic systems are more vulnerable to the aging process, thus providing valuable clues for their protection and/or corrective pharmacological treatments.