Alan C. Rosenquist - US grants

The proposed studies seek to understand how cortical and midbrain centers interact in mediating visually guided behaviors and how this interaction may be important for our ability to restore visual capacities in the cortically blind animal. The ability of an animal to detect and orient towards a novel stimulus (the "orienting response') is permanently lost in the blind hemifield opposite to a large cortical lesion. Destruction of the crossed subcortical pathway from the substantia nigra "critical zone" to the superior colliculus results in a rapid recovery of the orienting response in the previously blind hemifield. We propose: 1) to study the origin of the pathways that produce the recovery as they course through the commissure of the superior colliculus; 2) to study the input and output connections of that zone of the substantia nigra responsible for the recovery; 3) to test the hypothesis that the ipsilateral substantia nigra also may play a role in visual recovery; 4) to learn if pharmacological agents applied to the substantia nigra or superior colliculus will produce either a recovery or loss of visual orienting, and 5) to learn why neurotoxin lesions of one superior colliculus produce an enduring loss of vision that appears indistinguishable from cortical blindness. It is now clear that the visual cortex is neither necessary nor sufficient for visual orientation behavior in the cat. It is also clear in all species thus far studied that the substantia nigra, pars reticulata exerts a powerful inhibitory effect on cells in the deeper layers of the superior colliculus which function to mediate visuomotor behaviors such as the orienting response. Our ability to produce or eliminate a hemifield blindness or neglect by activation or inactivation of this and related subcortical circuits point to their importance in normal vision and may lead to therapeutic interventions in humans suffering from syndromes of sensory loss or neglect, e.g. cortical blindness. Finally, this work adds to our recent appreciation that the nigrotectal connection is a major output pathway by which the basal ganglia control sensorimotor functions.

Extrageniculate visual pathways and extrastriate visual cortex are important for vision. In light of new knowledge of cortical visual areas based upon mapping and connectivity studies we propose to study the interactions of cortex and midbrain and the roles of specific cortical areas in the learning, retention, and interhemispheric transfer of visual form discrimination and visually guided behavior. In Experiment I we shall make large unilateral lesions of the suprasylvian cortex in cats in which the optic chiasm has been split longitudinally. We shall confirm the observation of deficits in both learning and interhemispheric transfer, and attempt to localize the specific cortical area(s) responsible. We shall then remove the superior colliculus opposite the cortical lesion to test for possible improvement in these visual functions which might be analogous to the "Sprague Effect". In Experiment 2, using split chiasm cats, we shall make smaller suprasylvian lesions that produce no learning deficit by themselves; yet when combined with corpus collostomy result in learning deficits. This implies that cortex contralateral to the lesion "assists" the injured side. We shall then attempt to localize the contralateral area(s) responsible by selective ablation rather than callosotomy and to remove the superior colliculus opposite the original lesion to see if visual function improves. In both experiments 1 and 2 we shall repeat many of the procedures in cats with one optic tract sectioned. Experiment 2 will involve an anatomical study of all cats used in Experiments 1 and 2. Using HRP injected HRP into intact cortical areas, we shall determine whether the cortical lesions had resulted in the retrograde loss of cells in the LP-pulvinar complex whose axons branched and also projected to intact cortex.

bioimaging /biomedical imaging