Neurotoxicity of Methylmercury in the Visual Cortex

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DESCRIPTION (provided by applicant): Methylmercury (MeHg) is an environmental neurotoxicant that is responsible for several massive chronic and acute poisoning events occurred in the past. Mercury pollution remains a major environmental concern for public health, particularly for populations with high-fish diet and pregnant and nursing women. This concern has been heightened due to recent reports that dietary consumption of MeHg contaminated seafood is associated with greater potential risk of neurotoxicity than we previously thought. Acute and chronic MeHg exposure disrupts sensory and motor functions and causes severe neurotoxicity in humans and animals. One of the most consistent manifestations of MeHg poisoning in humans and animals is the visual functional disturbance. This is characterized by a concentric constriction of the visual fields - the peripheral visual sensitivity is lost whereas the central vision is virtually unaffected. Corresponding to the visual deficits are region-selective pathological lesions in the visual cortex. The underlying mechanisms for these impairments remain poorly understood, although it appears that the MeHg-induced visual deficits originate in the visual cortex. MeHg-induced region-selective pathological alterations in the visual cortex are thought to be responsible for the permanent loss of the peripheral visual fields. However, visual functional disturbances often occurred in the absence of or proceeding pathological changes in the visual cortex. Thus, the visual deficits could be due to MeHg-induced temporary disruption of certain neuronal function in the visual cortex. We hypothesize that MeHg may preferentially affect synaptic function of a specific population of neurons in the visual cortex. The long-term objective of this project is to understand the cellular and molecular bases for MeHg-induced region-selective neurotoxicity in the visual system. As an initial step, the present project is designed specifically to determine if MeHg preferentially affects synaptic function of certain populations of neurons in the visual cortex. The specific aims are to determine if neurons and their associated synaptic function in a particular region or layer of the visual cortex are affected selectively by MeHg and if GABAergic responses are more sentitive to MeHg than are glutamatergic responses. This study could be the first one designed specifically to examine the chronic effects of MeHg on the central visual function. Results of this study will provide specific information about the selective neurotoxicity of MeHg in the visual system.