Audie Leventhal - US grants

I propose to study the morphology of retrogradely labeled gaglion cells in retinae of cats, ferrets, New World monkeys (Saimiri sciureus), and Old World monkeys (Macaca fasicularis) following small electrophoretic injections of horseradish peroxidase (HRP) into regions of the brain that receive retinal afferents. The development of the morphology and radial orientation of the dendritic fields of retinal gaglion cells in cats, ferrets, New World monkeys and Old World monkeys will also be studied. In addition, the dedritic field morphologies and receptive field properties of functionally identified retinal gaglion cells will be studies in cats. Finally, I will determine whether the systematic relationship between preferred orientation and receptive field position found in cat visual cortex is also found in striate and extrastriate cortes of primates. The experiments will be carried out using histochemical procedures.which stain the cell bodies, axons and dendrites of gaglion cells labeled by extracellular and intracellular injections of horseradish peroxidase. The receptive field properties of visual neurons will be studied using standard extracellular and intracellular single unit recording procedures and a computerized optical display. Neuronal structure will be studies using a computerized morphometry system. These studies will help to (1) develop a morphological classification of retinal gaglion cells in the cat a monkey which can be related to the functional classification of different classes of retinal gaglion cells in these species, (2) determine which aspects of retinal gaglion cell morphology are responsible for the orientation sesitive response of retinal ganglion cells, and (3) clarify how dedritic field morphology and orientation develops in the retina and affects the organization of visual cortex

DESCRIPTION: (Investigator's abstract): The application's broad, long-term objectives are to increase our understanding of the functional organization of the visual pathways. The aims of Experiment I and II are to study the retinal, cortical, and intrageniculate contributions to the orientation sensitivity of different types of LGNd relay cells in cats and monkeys, respectively. The aim of Experiment III is to alter the distribution of retinal ganglion cell dendritic field orientations in newborn cats and then, in the adult, to study the orientation sensitivity and morphologies of the altered retinal ganglion cells and the LGNd relay cells and cortical cells which subserve them. The aim of Experiment IV is to study the proportion and distribution of orientation sensitive cells in layer 4c beta of monkey striate cortex. The relationship between the orientation biases of layer 4c beta cells and the orientation preferences of the simple and complex cells in the layers above and below them will also be studied. The experiments will be carried out using standard surgical procedures and computer controlled, quantitative procedures for studying the visually evoked responses of single cells in the visual pathways. Cortical inactivation and the simultaneous recording of action potentials and S potentials will be used to infer the relative contributions of cortical afferents, retinal afferents and intrageniculate mechanisms to the responses of LGNd relay cells. HRP histochemistry, DiI fluorescence labeling, and computerized morphometric analyses will be used to study neuronal morphology. Statistical tests designed specifically to analyze our data will be employed. The proposed studies should 1) increase our understanding of the functional organization of the LGNd, 2) elucidate the function of the corticogeniculate projection, 3) clarify the relationship between cortical and subcortical orientation sensitivity, and 4) provide information which will help us to better understand how form and color are encoded in the M and P cell pathways in primates.

DESCRIPTION (Adapted from Applicant's abstract): 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.