LEAD NEUROTOXICITY IN THE VISUAL SYSTEM

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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.