Irving Diamond - US grants

The evolution of neocortex in primates culminating in man is the most remarkable transformation in all of evolutionary history. In the traditional view the expansion of cortex was attributed to the increase in association areas. This conclusion has been reexamined over the past 15 years by the study of a graded series of species including opossum, hedgehog, tree shrew, and galago. These studies have shown that there is little or no association cortex as far up the scale as the prosimian. Instead the neocortex is composed chiefly of three extensive sensory fields: auditory, somatic and visual. The present proposal is aimed at uncovering the principles underlying the organization of these fields. At a first approximation it would seem that some principles are common to all fields. Each cortical field is the target of parallel pathways that differ in fiber size, relay in different thalamic nuclei, terminate in different layers of cortex, and to some extent terminate in different areas of the field. The aim of the research is to discover the functional significance of the various pathways by the behavioral deficit method. Because pathways overlap in a given cortical area, it is not easy to eliminate a pathway selectively by ablating a cortical area. Experiments are proposed in which separate paths are selectively destroyed. These studies will cast light on the role of the striate cortex and superior colliculus in vision. The evolution of cortex between the stages represented by prosimians and simians will be studied by adding the owl monkey to the series of species.

The starting point of this proposal is a number of behavioral studies of the extrastriate visual cortex: In Tupaia bilateral removal of the striate cortex leaves form vision preserved to a remarkable extent, but a removal of striate and extrastriate visual cortex combined greatly prolongs learning of simple visual tasks, and lesions of the extrastriate alone produce deficits in visual learning. In Galago there is evidence that the temporal cortex also has a role in visual learning, but the exact area has never been defined in either species. The significance of these results lies in the discovery in the cat that the ablation of the middle suprasylvian area has a profound effect on transfer of training from one to the opposite hemisphere as well as on visual learning. Just the same combination of deficits--retarded visual learning and deficits in hemispheric transfer--are found in the monkey by lesion of the inferotemporal cortex. What is the significance of this correlation between hemispheric transfer and visual learning? That is the question posed in this application. The method is first to identify precisely an extrastriate visual learning area in Tupaia and Galago, and second to study this area with behavioral tests of hemispheric transfer. Physiological and anatomical studies of the role of the commissures in the function of the extrastriate cortex are also proposed. We already know that the function of the extrastriate visual area in the cat does not depend on striate cortex, while the opposite is true of the monkey. This species difference suggests the possibility of convergent evolution and our studies of two carefully chosen species, Tupaia and Galago, are designed to explain the puzzling similarities and differences between the cat and monkey.

The objective is to understand the relation between the sensory and association areas of the neocortex. Since the neocortex is the hallmark of man, the research proposed promises to reveal the neural basis for perception, learning and cognition. The proposal is to continue using the three shrew (Tupaia glis) as a model for higher primates. Earlier studies in this laboratory showed that the association visual cortex in Tupaia is the target of a sensory pathway originating in the tectum and relaying in the pulvinar nucleus. Tupaia provides a unique opportunity to learn more about the functional relation between th tecto-pulvinar and the geniculo-striate pathways because the behavioral deficits after ablation of either pathway alone is not incapacitating. Behavioral experiments are proposed to test acuity, pattern vision, and visual learning after ablation of the pulvinar nucleus or the striate cortex. Anatomical experiments are proposed to identify subdivisions of the pulvinar nucleus in Tupaia and their connections to cortex. Immunocytochemical and HRP transport studies are proposed to learn more about the projections of the reticular formation to the dorsal thalamus (and to the lateral geniculate and pulvinar nuclei, in particular). The use of antisera will identify terminals according to their neurotransmitter; serotonin, acetylcholine, and noradrenalin. Galago and Saimiri will be used in addition to Tupaia. Finally, it is proposed that the study of the laminar organization in striate cortex of lateral geniculate terminals be continued using the methods of intracellular injection and electron microscopy.