DEGRADATION OF CORTICAL FUNCTION IN SENESCENT MONKEYS

衰老猴皮质功能的退化

• 批准号: 6488852
• 负责人: Audie Leventhal
• 金额: $ 34.13万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6488852
• 关键词: Macaca mulatta; age difference; animal old age; behavioral /social science research tag; brain electrical activity; brain mapping; cytochrome oxidase; developmental neurobiology; direct cortical response; electrophysiology; immunocytochemistry; lateral geniculate body; morphometry; neuroanatomy; neurophysiology; retinal ganglion; visual cortex; visual perception; visual stimulus

DESCRIPTION (Adapted from Applicant's abstract): Human visual function declines with age. Much of this decline is associated with neuronal changes in the central visual pathways. The purpose of this proposal is, for the first time A highly experienced, productive, and innovative investigator proposes to determine what changes in the visual system account for age-related declines in visual performance. The central hypothesis is that the most relevant alterations in the system occur in visual cortex rather than in the eye, retina, or LGN. Impressive preliminary results from aged and young monkeys support that contention. An array of related experiments are now proposed to evaluate possible changes in the properties of neurons in primary visual cortex, and possible changes in neurotransmitter expression in cortex, and relate these findings to visual behavior in the same monkeys, as well as to possible alternations in the LGN and eye. In this resubmission, less relevant approaches using optical imaging and studies of higher-order cortical neurons are left out, while the more relevant behavioral experiments have been added. While there has been some concern that much of the work is descriptive, the PI correctly points out that in fields of new endeavor, a careful description of basic findings is essential to further conceptual progress. As a minor concern, the behavioral experiments could have been presented in more detail. This research will take almost full time for one investigator, and the PI did not explain whom this individual might be. We suggest that these experiments might be more successful if the PI is able to recruit a postdoctoral fellow with previous experience in training and testing, to compare the functional organization of visual cortex in young and old monkeys. Three experiments are proposed. Preliminary data leaves no doubt that the proposed studies will yield valuable, clinically relevant data. Experiment 1 will compare, in young and old monkeys, the receptive field properties of cells in cortical area V1 (striate cortex). The properties to be studies include spontaneous activity, spatial resolution, contrast sensitivity, linearity of response, velocity sensitivity, binocularity, orientation sensitivity, direction sensitivity, receptive field size and receptive field organization (on and off sub-fields), response onset and peak, visual latencies, response strength and response variability. Care will be taken to assign cells to 1) different cortical layers and 2)different functional compartments as determined by cytochrome oxidase staining. Age related changes in receptive field properties will be related to the well documented changes in visual function associated with age (see background and significance). The effects of age upon a number of transmitter systems will be inferred by determining the amino acid signatures of cell bodies in the retina, LGNd and V1 of old and young monkeys. Finally, old animals will be studied at different ages and the time course of age-related changes as well as the degree of variability among old animals will be studied. Experiment 2 will determine the effects of age upon the subcortical visual pathways. The morphology and distribution of retinal ganglion cells projecting to the dorsal lateral geniculate nucleus (LGNd) will be determined. The physiological properties of LGNd cells will be studied if the corresponding properties of layer 4 V1 cells are abnormal. Similarly, if the properties of LGNd cells are abnormal than the physiological properties of retinal ganglion cells will be studied. The results of this study will provide insight into the extent that cortical abnormalities in aged animals reflect subcortical changes. Experiment 3 will determine the visual capabilities of senescent monkeys of different ages. Since the orientation, direction, contrast and spatial frequency sensitivities of V1 cells are affected by age (see preliminary results), these abilities will be stressed. The visual capabilities of individual old monkeys will be related to the degradation of these specific receptive field properties of their V1 cells.

描述（改编自申请人的摘要）：人类的视觉功能下降 随着年龄的增长。这种下降的大部分与神经元变化有关 中央视觉途径。该提议的目的是首次 经验丰富，富有成效和创新的研究者建议 确定视觉系统中的变化是与年龄相关的下降的原因 视觉性能。中心假设是最相关的 系统中的改变发生在视觉皮层而不是眼中， 视网膜或LGN。年迈和年轻猴子的令人印象深刻的初步结果 支持这一争论。现在提出了一系列相关实验 评估主要视觉中神经元特性的可能变化 皮质，以及皮质中神经递质表达的可能变化，以及 将这些发现与同一猴子中的视觉行为相关联 LGN和眼睛中可能的交替。 在此重新提交中，使用光学成像和 遗漏了高阶皮质神经元的研究，而更相关 已经添加了行为实验。尽管有一些担忧 大部分工作都是描述性的，PI正确地指出了 新的努力，对基本发现的仔细描述对于进一步 概念进步。 作为小问题，行为实验可能已在 更多细节。这项研究几乎需要一位调查员的全职时间，以及 PI没有解释这个人可能是谁。我们建议这些 如果PI能够招募A，则实验可能会更成功 博士后研究员，具有以前在培训和测试方面的经验， 比较年轻的和老猴子中视觉皮层的功能组织。 提出了三个实验。初步数据毫无疑问 拟议的研究将产生有价值的临床相关数据。实验1 将在年轻人和老猴子中比较细胞的接受场特性 在皮质区域V1（条纹皮层）中。作为研究的特性包括 自发活动，空间分辨率，对比度灵敏度，线性的线性 响应，速度敏感性，双向性，方向灵敏度， 方向敏感性，接受场大小和接受场组织 （在接门子场），响应发作和峰值，视觉潜伏期，响应 力量和响应变异性。注意将细胞分配到1） 不同的皮质层和2）确定的不同功能隔室 通过细胞色素氧化酶染色。接收场与年龄相关的变化 属性将与文化良好的视觉功能变化有关 与年龄相关（请参阅背景和意义）。年龄对 通过确定氨基酸，可以推断出许多发射器系统 旧猴子和年轻猴子的视网膜，LGND和V1中的细胞体特征。 最后，将在不同年龄和时间过程中研究老动物 与年龄相关的变化以及旧动物之间的可变性程度将 被研究。实验2将确定年龄对皮层的影响 视觉途径。视网膜神经节细胞的形态和分布 将确定投影到背侧侧向基因核（LGND）。 如果相应的 第4层V1细胞的特性是异常的。同样，如果特性 LGND细胞比视网膜神经节的生理特性异常 细胞将被研究。这项研究的结果将为您洞悉 老年动物的皮质异常反映了皮质下变化的程度。 实验3将确定衰老猴子的视觉能力 不同的年龄。由于方向，方向，对比和空间 V1细胞的频率敏感性受年龄的影响（请参阅初步 结果），这些能力将得到强调。视觉功能 单个旧猴子将与这些特定的降解有关 其V1细胞的接受场特性。