AGED-RELATED CHANGES IN CORTICAL CIRCUITS IN HUMANS

本申请是对计划公告PA-92-07的响应 神经系统与心智、神经和衰老研究助学金 精神错乱。拟议研究的目标是确定如何 人类视皮层中的功能回路是如何发展起来的 电路会随着年龄的增长而变化。这些问题将由 在乙醛固定的死后人脑中追踪与 荧光染料，DII。这是我们最先引进的一项技术 用于研究人脑中的电路(Burkhalter和Bernardo，1989)。 这项研究将重点放在视觉皮质的连接上，而不是因为 了解视力或视觉障碍是这里的主要兴趣，但 因为这是CNS中唯一一个其功能架构 充分理解有意义的结构/功能关系 可以派生出，正常连接模式中的微小变化 可以被检测到。如果成功，预计这项研究将 提供有关一些重要问题的信息。它将显示L) 人类大脑中的微电路可以通过实验方法进行研究， 2)神经元电路以预先编程的顺序发展，这决定了 特定功能的成熟，3)皮质连接的改变 在整个生命周期内，4)连接更改仅限于系统 在生命后期发展，其发展可能受到强烈影响 凭经验。 这项建议是基于对人类初级视觉的初步研究 皮质(VI)，揭示了三个主要发现：1)局部联系 在皮质柱内，产前发育，2)水平连接 柱子之间在出生后发育的方式是与 运动处理通路在回路更紧密之前发展 与形式和颜色分析相关联，以及3)层状组织 对纹状皮质的反馈投射在老年人中选择性地改变 大脑。本申请中提出的实验主要集中在 V1、第二视觉区域V2内的水平连接和反馈 V2和V1之间的投影。具体来说，我们将确定：1)如何 本地连接在V2内形成，2)是否出现反馈连接 在正向预测之前，3)反馈预测是否在 老化的大脑，4)V1内的局部连接是否随着 生命的跨度。这些连接的共同点是它们允许 大脑皮层内比较视野的远点。这 属性对于将图形从其周围分割出来是必不可少的。 心理物理测试表明，需要整合的视觉任务 大部分的视野直到1岁才发育。 并随着年龄的增长而恶化。因此，这些变化有可能 是由于V1、V2内远程连接的更改或修改 从V2到V1的反馈输入。类似的联系在以下方面可能很重要 其他皮质区域，它们可能是感觉-运动整合的基础或 提供跨功能不同系统的集成。

This application is in response to the program announcement PA-92-07 for research grants on Neural Systems and Mental, Neurological and Aging Disorders. The goal of the proposed research is to determine how functional circuits develop in the human visual cortex and how these circuits change with advancing age. These questions will be approached by tracing connections in the aldehyde fixed, postmortem human brain with the fluorescent dye, DiI. This is a technology which we have first introduced for studying circuits in the human brain (Burkhalter and Bernardo, 1989). The study will be focused on connections in the visual cortex, not because understanding vision or visual disorders are the main interest here, but because this is the only system in the CNS whose functional architecture is understood well enough that meaningful structure/function relationships can be derived, and small alterations in the normal connectivity pattern can be detected. If successful, it is anticipated that the study will provide information on a number of important issues. It will show that l) microcircuits in the human brain can be studied by an experimental method, 2) neuronal circuits develop in a preprogrammed sequence which determines the maturation of specific functions, 3) cortical connections change throughout life, and 4) connectivity changes are restricted to systems that develop late in life and whose development may be strongly influenced by experience. The proposal is based on preliminary studies in the human primary visual cortex (VI) which revealed three principal findings: 1) local connections within cortical columns develop prenatally, 2) horizontal connections between columns develop postnatally in a manner that circuits related to the motion processing pathway develop before circuits the are more closely associated with form and color analysis, and 3) the laminar organization of feedback projections to striate cortex is selectively altered in aged brains. The experiments proposed in this application are focused on horizontal connections within V1, the second visual area V2 and feedback projections between V2 and V1. Specifically, we will determine: 1) how local connections form within V2, 2) whether feedback connections emerge before forward projections, 3) whether feedback projections are altered in aged brains and, 4) whether local connections within V1 change over the span of life. These connections have in common that they allow the intracortical comparison of distant points of the visual field. This property is essential for the segmentation of a figure from its surround. Psychophysical tests indicate that visual tasks that require integration over large portions of the visual field do not develop until 1 year of age and deteriorate with advanced age. Thus, it is possible that these changes are due to alterations of long-range connections within V1, V2 or modified feedback input from V2 to V1. Similar connections may be important in other cortical areas where they may underlie sensory-motor integration or provide for integration across functionally different systems.