Synaptic Alterations in the Cerebral Cortex during Aging

描述(申请人提供)：人类物种的衰老过程导致高级中枢神经系统功能的恶化。大脑皮层神经元及其突触所经历的与年龄相关的变化是老年认知缺陷的核心。然而，很少有实验数据确定哪些新皮质神经元和哪些突触在结构或功能上受到最大影响，以及在哪个时间序列中受到影响。该项目将检验以下假设：1)大锥体神经元比非锥体皮质神经元对衰老过程更敏感，2)认知受损老年人的新皮质可能存在兴奋和抑制锥体神经元影响之间的失衡。为了验证上述假设，一个多学科团队将应用行为、生理(单细胞电生理学、膜片钳)和形态(细胞内标记神经元的光镜和电子显微镜免疫细胞化学)研究相结合的研究，以确定哪些特定的大脑皮层神经元受衰老的影响最大，它们的突触模式是什么，以及与记忆受损的老年动物相比，老年动物的兴奋性和抑制性突触放电之间是否存在失衡。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/或纠正性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.