Helen Sherk - US grants

This proposal concerns the function of the reciprocal loop connecting the visual claustrum and the visual cortex. Descriptions now exist of the response properties conveyed by the return limb of this loop, from claustrum to cortex, and its terminal distribution is also known. The most interesting question, that of the function of the cortico-claustral loop, remains to be answered. I intend to study this using three different methods. First, I will destroy the claustrum and assess the resulting changes in areas 18 and 19. This project is an extension of work carried out by Simon LeVay and myself on area 17, in which we demonstrated specific and reproducible alterations in the response properties of some cells following loss of claustral input to the cortex. Second, I will reversibly inactivate the claustrum using lidocaine and examine the consequences of loss of claustral input for single cells. In such experiments each cell will serve as its own control, rendering the method considerably more sensitive than ones dependent on irreversible lesions. Cells will be studied in areas 18 and 19, and then, depending on results in these areas, in areas 17 or PMLS, or both. Third, I will ask whether claustral axons branch to innervate more than one cortical area. To do so I will use two retrograde tracers in single experiments. One of these will be horseradish peroxidase, and the other, a tracer visualized autoradiographically. The discovery of the claustrum's function in visual cortical information processing should contribute significantly to our understanding of the generation of cortical response properties, a topic that had produced considerable interest but few definite answers. Moreover, this information might suggest what role the claustrum plays in other sensory modalities.

DESCRIPTION (adapted from abstract): Vision plays an essential role during normal locomotion. In elderly people, decreased visual capacity is a major contributing factor to falls that often result in serious injury. The present proposal has two goals. First, the intent is to explore the neural mechanism underlying visual analysis during locomotion in an animal model. Second, the aim is to investigate visual function during locomotion. The cat will be used as a model both for electrophysiological study of single neurons and in behavioral testing. The cat is suitable for several reasons. First, the area of visual cortex to be targeted, LS, closely resembles a well-studied area of primate cortex, MT. Second, cats, like humans, locomote across 2-dimensional substrates and thus face similar challenges during locomotion. Third, cats are good subjects for behavioral assessment of visual function during locomotion; they are extremely sure-footed and use visual cues to guide paw placement when traversing a cluttered environment. To test the role of neurons in LS in visual guidance of locomotion, a novel stimulus display system has been developed. Computer-generated "optic flow" movies, 65x62 deg in size, are used that simulate the view of a cat locomoting through a natural environment. A wide range of such movies has been developed. To explore the mechanism by which neurons respond to particular objects embedded in optic flow movies, movies will be used in which the retinal acceleration and speed of objects relative to background will be manipulated independently. To investigate why normal direction-selectivity appears to be suppressed when viewing optic flow movies, the optic flow background will be altered, resulting in both plausible optic flow (as when the cat tracks a point on the ground) and anomalous flow (as when acceleration or expansion cues are eliminated). To see whether neurons respond selectively when the cat makes a turn, movies simulating left and right turns of various sizes will be used. Finally, we will test whether neurons respond to small objects and irregularities directly in the cat's path that cause adjustment in paw placement during real locomotion. Behavioral experiments will explore the range of objects and irregularities that cause stride adjustment. Most importantly, they will be used to test visual function during locomotion after lesions of LS to directly assess this area's contribution to visual guidance of locomotion.