AGED-RELATED CHANGES IN CORTICAL CIRCUITS IN HUMANS

本申请是对PA-92-07项目公告的回应， 神经系统和精神，神经和衰老的研究赠款 精神失常。这项研究的目的是确定如何 功能电路在人类视觉皮层中发展， 电路随着年龄的增长而变化。这些问题将由以下人员处理： 追踪醛固定的死后人脑与 荧光染料DiI。这是我们首次引进的技术 研究人类大脑中的回路（Burkhalter和Bernardo，1989）。 这项研究将集中在视觉皮层的连接上，而不是因为 理解视觉或视觉障碍是这里的主要兴趣， 因为这是中枢神经系统中唯一一个 被充分理解，有意义的结构/功能关系 可以推导出，正常连接模式的微小变化 可以被检测到。如果成功，预计研究将 就一些重要问题提供信息。这将表明，l） 人脑中的微电路可以通过实验方法来研究， 2)神经元回路以预先编程的顺序发展， 特定功能的成熟，3）皮质连接改变 4）连接性变化仅限于系统 在生命后期发展，其发展可能受到强烈影响 凭经验 该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）局部连接 在皮质柱内产前发展，2）水平连接 在出生后， 运动处理路径在电路之前发展， 与形式和色彩分析相关，以及3）层状组织 老年人纹状体皮质的反馈投射选择性改变， 大脑本申请中提出的实验集中在 V1、第二视觉区域V2和反馈内的水平连接 V2和V1之间的投影。具体来说，我们将确定：1）如何 V2内部形成局部连接，2）是否出现反馈连接 在前向预测之前，3）反馈预测是否被改变， 老化的大脑，以及，4）V1内的局部连接是否随着年龄的增长而改变。 寿命跨度。这些连接的共同点是，它们允许 视野远点的皮质内比较。这 属性对于从其周围分割图形是必不可少的。 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 随着年龄的增长而恶化。因此，这些变化可能 是由于V1、V2内的远程连接的改变或修改 从V2到V1的反馈输入。类似的联系可能很重要， 其他皮层区域，它们可能是感觉-运动整合的基础， 提供跨功能不同的系统的集成。

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.