Jon H. Kaas - US grants

The proposed research seeks to determine variables important in the loss or preservation of ganglion cells of the retina after cortical lesions as a consequence of transneuronal retrograde degeneration in primates and other mammals. After longstanding cortical lesions produce such ganglion cell loss, the projection patterns of the remaining ganglion cells will be studied by autoradiographic procedures. These studies will document the conditions of ganglion cell loss, lead to a better understanding of the phenomenon of transneuronal retrograde degeneration, and provide basic information on the central connections of different cell classes of the retina.

The proposed integrative, systems level somatosensory research addresses three major goals. 1) We will determine how the developing and mature somatosensory systems of primates reorganize after major losses of sensory afferents. In a preliminary study, we demonstrated that dorsal column lesions in monkeys result in a moderate to massive reorganization of somatosensory cortex. In a series of new experiments, branches of peripheral nerve afferents will be cut as they rise in the dorsal columns of the spinal cord, and reorganizations and mechanisms of reorganization will be studied at cortical and subcortical levels after complete or incomplete removals of hand afferents. Lesions in newborns are expected to lead to more extensive and possibly different recoveries. Partial sections are expected to lead to more rapid and more functional recoveries. Evaluation processing include state-of-the-art multisite recordings from chronically implanted microelectrodes. 2) Related experiments will investigate cortical organization after partial or complete lesions of hand cortex in area 3b. For both types of studies, the response properties of altered neurons, and behavioral impairments and recoveries will be evaluated. The roles of the growth of new connections and histochemical changes in recovery will also be studied. 3) We plan to advance our basic understanding of the functional organization of the somatosensory system of primates by determining the connections of two areas of somatosensory cortex, discovered in our laboratory, PV and VS, and compare these connections with those of other areas in the same animals. In addition, we will compare the chemorchitecture of somatosensory and motor cortex in monkeys, chimpanzees, and humans to help identify valid subdivisions of cortex in humans and reveal human specialization. These three types of studies will provide a) an understanding of the scope and mechanisms of plasticity in the developing and mature somatosensory system that can guide programs of therapy in humans, and b) a more detailed and comprehensive understanding of the organization of the somatosensory system in primates that is especially relevant to humans and as a guide for future research.

DESCRIPTION (provided by applicant): The goal of this proposal is to determine how posterior parietal cortex (PPC) of primates is organized and functions in sensorimotor behavior. Posterior parietal cortex is currently thought to play a critical role in the planning and the initiation of various sensory guided behaviors such as reaching, grasping, and looking, while providing outputs to premotor and motor cortex that organize the motor behaviors. Over the last grant period we have greatly extended this important framework by providing clear evidence that approximately 7-8 different subregions or domains of PPC initiate different classes of movements when electrically stimulated in monkeys and other primates (grasping, reaching, looking, head defense, body defense, aggressive expression, climbing). Moreover, we defined functionally matching domains in premotor cortex and primary motor cortex where matching classes of complex movements are evoked by electrical stimulation. We have identified anatomical connections between matching domains, and visual and somatosensory inputs to PPC domains. We now plan experiments to reveal the functional relationship between matched PPC and motor domains, how domains of different types interact, and how domains differ in the proportions and types of visual and somatosensory inputs they receive to guide motor behaviors. We also expect to determine if matching or electrically evoked behaviors recover after we lesion specific domains, and if so, how the brain reorganizes to mediate behavioral recoveries. Our methods of investigation include electrical microstimulation of domains, the chemical inactivation or potentiation of domains, the reversible inactivation of domains with a cooling probe, behavioral studies after lesions of domains, the recordings of neural activity with arrays of microelectrodes, and the use of anatomical and histological methods to reveal brain connections and structural subdivisions of the cortex. The results are expected to produce a new and greatly expanded understandings of the functional organization of PPC in primates, how functional domains in PPC interact with each other, how they are guided by sensory information, and how they mediate different classes of behaviors by activating matching parts of frontal motor fields. The results will lead to a better understanding of the impairments that resul in humans after PPC damage, and indicate the levels and time courses of recovery. The results will also suggest modes of clinical treatment that are open to experimental validation.

DESCRIPTION: (ADAPTED FROM THE APPLICANT'S ABSTRACT) The long-term objectives of this project are to describe (1) the subdivisions of auditory cortex in primates, (2) their connection patterns with the frontal lobe and limbic system, and (3) the convergence of visual and auditory pathways. All three objectives will be investigated by combining microelectrode recordings and anatomical techniques in parallel experiments on New World owl monkeys (for their relatively unfissured and easily accessible cortex), and Old World macaque monkeys (for their close phylogenetic relation to humans). A major focus of this project is to study the cortical and thalamic connectivity of AI, R (or RL), and the surrounding auditory belt cortex. This will be accomplished by placing injections of 2-3 different tracers into AI and R using best frequency maps, and single neuron selectivities to sound direction and level to identify injection sites. The results will provide information on the topographic organization of thalamic and cortical connections of AI and R with respect to tonotopic organizations and representations within an isofrequency contour. Subdivisions of the belt cortex defined by their connection patterns with AI and R, will then be injected and their connections with more distant areas of auditory cortex, frontal lobe and limbic structures examined. The data gathered from these multiple injections in the belt cortex and adjacent auditory fields, will lead to the third major goals of this project, which is to define areas of convergence of visual and auditory information. In these experiments, injections of different tracers in regions of cortex identified as visual or auditory by electrophysiological recording and/or connections with physiological maps of visual and auditory cortex will provide information on the origin and interaction of the two sensory systems in the cortex and thalamus of primates.

9500863 Kaas This U.S.-Brazil Cooperative Science Program award supports travel expenses, expendable research supplies and services, related to the visits of Drs. J. Kaas, the P.I. and his co-P.I.s, all from Vanderbilt University, Tennessee, to the lab of Dr. C. E. Rocha Miranda, Univ. Federal de Rio de Janeiro, Brazil. The purpose of the research is to develop a model of how simple, primitive mammalian brains are organized, in terms of functionally significant areas, nuclei and modules that are interconnected within cooperative systems. This model can be compared to those based on complex, advanced brains, such as those of higher primates, to determine changes associated with complexity and enhanced performance. The model will be based on data obtained from experimental studies on North and South American opossums. The brains of these Metatherian mammals have changed little in external appearance, judging from the brain endocasts of early mammals, since the major radiation of mammals some 65 mya, and they provide the clear advantage of availability near both the U.S.A. and Brazilian laboratories. Previous comparative studies provide direct evidence that the basic brain organization of opossums is less complex and more primitive than that of most extant mammals, and that further studies using a powerful range of modern techniques could provide valuable additional insights. The research will involve studies of the visual, auditory and somatosensory systems that involve the majority of neurons in neocortex, and address critical issues of motor system organization, where Metatherian mammals may be less complex than Eutherian mammals. Microelectrode recordings will be used to identify systematic representations of sensory surfaces in the brain and microstimulation methods will reveal movement centers. Brain subdivisions, identified with microelectrodes, will be further examined for histochemical, architectonic, and molecular distinctions, intern al microorder and patterns of connection with other systems. The research plan takes advantage of the extensive previous experience of researchers in the Brazilian laboratory in studies of the brains of opossums, and their unique experience in characterizing the response properties of neurons in sensory systems of opossums. The researchers in the U.S.A. laboratory also have relevant experience in brain studies in opossums, as well as an extensive background in comparative studies of brain organization. Investigators in the two laboratories have both overlapping and complementary experience with research procedures and techniques, and a joint interest in understanding brain organization in opossums. A merger of efforts will allow for greater progress in the field. ***

bioimaging /biomedical imaging; computer graphics /printing

? DESCRIPTION (provided by applicant): The role of the thalamus in brain function has been somewhat neglected until relatively recently. This is particularly true of one of its most prominen components, the pulvinar. The goal of this proposal is to understand the functional subparts of the pulvinar and how they relate to different visual cortical areas. We argue that one of the reasons there has been so little progress in understanding the role of the pulvinar is that basic information is missing about its properties and connections with well-defined areas. Building on our recent work investigating the primate pulvinar, the key to functionally parsing the pulvinar is to use the retinotopic maps in pulvinar as the starting point just as retinotopic maps in cortex define functional areas in cortex. There are two well-defined retinotopic pulvinar maps that exist in the inferior and lateral pulvinar of all studied primates. To date, we still know very little abut their functions, and the differences between these two maps. We hypothesize that the two maps are biased to connect to dorsal and ventral stream visual cortical areas. These biases should allow separate cortical areas to purpose the two retinotopically defined mapped zones in distinct ways. We plan to test this hypothesis in the form of two aims. In aim 1 we propose three anatomical studies to define the details of the cellular, axonal and connectional differences between the two pulvinar maps as these relate to cortical visual areas V1, V2, V3, DL/V4 and MT/V5. In aim 2 we propose three physiological studies designed to compare the receptive field properties and their organization between the two retinotopically defined maps. We believe, taken together, these studies will provide the keys to parsing the primate pulvinar which, in turn, will provide the necessary tools to understand the functional significance of pulvinar and provide insights into thalamic control of visual information flow.