DEVELOPMENT OF INTRINSIC CIRCUITRY IN VISUAL CORTEX

视觉皮层内在回路的发育

基本信息

批准号：
2838295
负责人：
LAWRENCE C. KATZ
金额：
$ 14.73万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-12-01 至 2001-11-30
项目状态：
已结题

项目摘要

DESCRIPTION: Orientation selectivity in the mammalian primary visual cortex is a fundamental feature of cortical organization and function and is likely to provide a key to understanding the general rules of neocortical information processing. The original model for orientation selectivity, proposed by Hubel and Wiesel, in which orientation selectivity is based on the convergence of thalamic afferents, has received considerable experimental support. However, subsequent theories and experiments suggest that local cortical circuits, especially inhibitory connections, may also be critical. Little is known, however, about the structural and functional organization of inhibition as it relates to the organization of orientation columns in cortex. Two of the major aims of this proposal are to examine these relationships in ferrets, using a combination of in vivo imaging techniques to define orientation domains, and in vitro brain slices to probe the functional and structural of inhibitory circuits relative to these domains. Experiments using laser photostimulation, voltage-sensitive dye recordings, and intracellular staining are proposed to determine whether inhibition arises primarily form columns of the same or different orientations. Further photostimulation and voltage-sensitive dye imaging experiments are designed to examine whether one component of columnar circuitry, the layer 6 to 4 projection, could selectively amplify the orientation selectivity that is created by thalamic afferents. While patterning of thalamic inputs probably plays a fundamental role in generating orientation selectivity, how such patterning is achieved remains an open question. The role of spontaneous retinal activity in generating orientation selectivity will be tested by using new stimulation techniques to manipulate the levels and patterns of neural activity emanating from the retina during early postnatal development, and assessing the impact of these manipulations on the organization of orientation columns and orientation selectivity in cortex. Finally, as the approach of laser photostimulation has the potential for greatly accelerating the analysis of local circuits in the cortex and elsewhere, a series of experiments are proposed to develop a new, more general method of photostimulation, based on photolabile liposomes. This will enable researchers to deliver bioactive molecules with unprecedented spatial and temporal resolution. Understanding the basic computational circuits in cortex is fundamental to understanding the basis of numerous pathological states of cortical organization, including amblyopia and mental retardation, while determining the role of early spontaneous activity in constructing circuits has important implications for the effects of toxins and drugs during prenatal development in humans.

描述：哺乳动物主要视觉皮层中的方向选择性是皮质组织和功能的基本特征，很可能是为理解新皮质的一般规则提供关键信息处理。定向选择性的原始模型，由Hubel和Wiesel提出的，其方向选择性基于丘脑传入的融合，已获得相当大的实验支持。但是，随后的理论和实验表明当地的皮质电路，尤其是抑制连接，也可能是批判的。但是，关于结构和功能的知之甚少与方向组织有关的抑制组织皮质中的列。该提议的两个主要目的是检查这些关系在雪貂中，结合体内成像定义定向域和体外脑切片的技术相对于这些抑制回路的功能和结构域。使用激光光刺激，电压敏感染料的实验提出了记录和细胞内染色，以确定是否是否抑制作用主要形成相同或不同的列方向。进一步的光刺激和电压敏感的染料成像实验旨在检查柱状的一个组成部分电路，第6至4层投影，可以选择性地扩增由丘脑传入产生的方向选择性。尽管丘脑输入的图案可能在产生方向选择性，如何实现这种模式一个悬而未决的问题。自发视网膜活动在产生的作用方向选择性将通过使用新的刺激技术进行测试操纵从在产后早期发展期间的视网膜，并评估这些影响对定向列的组织和方向的操纵皮质中的选择性。最后，随着激光光刺激的接近有可能大大加速对本地电路的分析皮层和其他地方，提出了一系列实验来开发基于光值的新的，更通用的光刺激方法脂质体。这将使研究人员能够用空前的空间和时间分辨率。了解基本皮质中的计算电路是理解基础的基础皮质组织的许多病理状态，包括弱视和智力低下，同时确定早期的作用构建电路中的自发活动对人类产前发育过程中毒素和药物的影响。