Human visual function declines with age. Much of this decline is associated with neuronal changes in the central visual pathways. The purpose of this proposal is, for the first time A highly experienced, productive, and innovative investigator proposes to determine what changes in the visual system account for age-related declines in visual performance. The central hypothesis is that the most relevant alterations in the system occur in visual cortex rather than in the eye, retina, or LGN. Impressive preliminary results from aged and young monkeys support that contention. An array of related experiments are now proposed to evaluate possible changes in the properties of neurons in primary visual cortex, and possible changes in neurotransmitter expression in cortex, and relate these findings to visual behavior in the same monkeys, as well as to possible alternations in the LGN and eye. In this resubmission, less relevant approaches using optical imaging and studies of higher-order cortical neurons are left out, while the more relevant behavioral experiments have been added. While there has been some concern that much of the work is descriptive, the PI correctly points out that in fields of new endeavor, a careful description of basic findings is essential to further conceptual progress. As a minor concern, the behavioral experiments could have been presented in more detail. This research will take almost full time for one investigator, and the PI did not explain whom this individual might be. We suggest that these experiments might be more successful if the PI is able to recruit a postdoctoral fellow with previous experience in training and testing, to compare the functional organization of visual cortex in young and old monkeys. Three experiments are proposed. Preliminary data leaves no doubt that the proposed studies will yield valuable, clinically relevant data. Experiment 1 will compare, in young and old monkeys, the receptive field properties of cells in cortical area V1 (striate cortex). The properties to be studies include spontaneous activity, spatial resolution, contrast sensitivity, linearity of response, velocity sensitivity, binocularity, orientation sensitivity, direction sensitivity, receptive field size and receptive field organization (on and off sub-fields), response onset and peak, visual latencies, response strength and response variability. Care will be taken to assign cells to 1) different cortical layers and 2)different functional compartments as determined by cytochrome oxidase staining. Age related changes in receptive field properties will be related to the well documented changes in visual function associated with age (see background and significance). The effects of age upon a number of transmitter systems will be inferred by determining the amino acid signatures of cell bodies in the retina, LGNd and V1 of old and young monkeys. Finally, old animals will be studied at different ages and the time course of age-related changes as well as the degree of variability among old animals will be studied. Experiment 2 will determine the effects of age upon the subcortical visual pathways. The morphology and distribution of retinal ganglion cells projecting to the dorsal lateral geniculate nucleus (LGNd) will be determined. The physiological properties of LGNd cells will be studied if the corresponding properties of layer 4 V1 cells are abnormal. Similarly, if the properties of LGNd cells are abnormal than the physiological properties of retinal ganglion cells will be studied. The results of this study will provide insight into the extent that cortical abnormalities in aged animals reflect subcortical changes. Experiment 3 will determine the visual capabilities of senescent monkeys of different ages. Since the orientation, direction, contrast and spatial frequency sensitivities of V1 cells are affected by age (see preliminary results), these abilities will be stressed. The visual capabilities of individual old monkeys will be related to the degradation of these specific receptive field properties of their V1 cells.
Showing the most recent 10 out of 12 publications
