LEAD NEUROTOXICITY IN THE VISUAL SYSTEM

拟议的研究将检查低水平的神经毒性作用， 铅对视觉系统的影响 最近的临床和 实验研究表明，发育期的铅暴露会产生 长期视敏度（即，空间分辨率）缺陷， 暗视下观察到的变化（视杆细胞介导），而明视下观察到的变化 （视锥介导的），亮度条件。 本研究的目的 项目是定量描绘，在细胞水平上， 视网膜和皮层感受野特性的改变， 介导的空间分辨率。 在视网膜，单个细胞外 Long-Evans hooded大鼠的生理记录将确定 X和Y视网膜神经节细胞对空间分辨率的贡献 通过测量它们的感受野特性（例如，对比 敏感性、感受野中心直径）和轴突传导 轻泻药。 我们的生理发现与形态学的关系 将通过确定X射线的大小、数量和密度来检查变化 和Y（1）视网膜全标本中的细胞和（2）视神经中的轴突， 定量形态测量技术。 杆的微分影响 而视锥输入对感受野中心直径的大小将是 由局部（微电泳）应用确定 的药物显示，以区分这些输入下暗适应和明视 条件 在视觉皮层，单单位微离子电渗 实验将检验铅对感受野的影响 属性（例如，对比敏感度，感受野大小）的简单和 复杂的细胞，以确定神经元群体和机制 造成空间分辨率不足。 简单的改变和 复杂的细胞将与它们的功能组织有关， 单个皮质层，以评估皮质 根据已知的皮层微电路来运作。 受体 结合研究将检查改变的药理学基础。 在这些研究中确定的感受野特性。 的结果 这些相关的研究将提供视网膜的细胞数据， 负责空间分辨率的铅的皮质作用部位， 暗视觉缺陷 此外，这些研究将提供洞察力 负责视觉感知和阅读的机制 在接触低水平铅的儿童中观察到的残疾， 为可能的补救和成功的治疗程序提供想法。

The proposed studies will examine the neurotoxic effects of low-level developmental lead exposure on the visual system. Recent clinical and experimental studies show that developmental lead exposure produces long-term visual acuity (i.e., spatial resolution) deficits with greater alterations observed under scotopic (rod-mediated), than photopic (cone-mediated), luminance conditions. The objective of this research project is to quantitatively delineate, at the cellular level, the alterations in the retinal and cortical receptive field properties which mediated spatial resolution. At the retina, single-unit extracellular recordings in Long-Evans hooded rats will determine the physiological contribution of X and Y retinal ganglion cells to the spatial resolution deficit by measuring their receptive field properties (e.g., contrast sensitivity, receptive field center diameter) and axonal conduction latencies. The relationship of our physiological findings to morphological changes will be examined by determining the size, number and density of X and Y (1) cells in retinal whole mounts and (2) axons in optic nerve using quantitative morphometric techniques. The differential influence of rod and cone input on the size of the receptive field center diameter will be determined pharmacologically by the local (micriontophoretic) application of drugs shown to distinguish these inputs under scotopic and photopic conditions. At the visual cortex, single-unit microiontophoretic experiments wil examine the effects of lead on the receptive field properties (e.g., contrast sensitivity, receptive field size) of simple and complex cells in order to identify the neuronal population and mechanisms contributing to the spatial resolution deficit. Alterations in simple and complex cells will be related to their functional organization in individual cortical laminae to assess the consequences on cortical functioning in terms of the known cortical microcircuitry. Receptor binding studies will examine the pharmacological basis of the altered receptive field properties determined in these studies. The results of these correlative studies will provide cellular data on the retinal and cortical sites of action of lead responsible for the spatial resolution and scotopic vision deficits. In addition, these studies will provide insight into the mechanisms responsible for the visual perceptual and reading disabilities observed in children exposed to low-level of lead and thereby provide ideas for possible remediation and successful treatment procedures.