The long term goal of this research is to understand the decrease in plasticity during maturation of the mammalian nervous system. The investigators use the visual system to study this problem for two reasons. First, the visual system changes dramatically when an animal is deprived of a normal visual environment. These changes can be used to assess plasticity. Second, defects in the visual system of human infants cause permanent visual deficits unless these defects are corrected very early. Eventually, the investigators hope to find methods of maintaining plasticity in the human visual system that will permit later correction of visual deficits and other types of impairment due to environmental adversity. This proposal focuses on the role of N-methyl-d-Aspartate (NMDA) receptors in visual system plasticity. These receptors have been implicated in other types of plasticity. The investigators will use MK-801, a noncompetitive NMDA antagonist, binding as a marker for NMDA receptors. Pilot work has demonstrated that MK-801 receptors have their highest density during the period of maximum plasticity, and therefore, may have a role in determining when the visual system is plastic. The first group of experiments explores the relationship between NMDA receptor function and the decline of visual plasticity. In these experiments the investigators ask: (1) whether the development and decline of MK-801 binding sites parallels the development and decline of visual cortex plasticity; (2) whether the changes in MK-801 binding sites are specific to the visual cortex; (3) whether changes in binding sites are specific to the MK-801 binding site; (4) whether the laminar location of the binding sites changes with age; and (5) whether the properties of the binding size change with a time course similar to the time course of plasticity. All of the above questions will be approached with homogenate binding and with receptor binding autoradiography. The next group of experiments asks whether blockade of NMDA channels alters visual cortex plasticity. These experiments involve suturing one eye for about 12 days, and asking whether the effects of suture are modified by treatment with MK-801. The effects of suture will be assayed by recording from the visual cortex. The final group of experiments relates plasticity changes resulting from norepinephrine (NE) and acetylcholine (ACh) depletion to plasticity changes resulting from MK-801 treatment. Previous work has indicated that NE and ACh are also important for the maintenance of plasticity. The first experiments in this group ask whether NMDA stimulated NE and ACh release changes with age, whether this release is modified by in vivo MK-801 treatment, and whether any modification is age dependent. The second experiments ask whether depletion of NE and ACh alters the number and distribution of NMDA receptors.
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