1985 — 2004 |
Van Hoesen, Gary W |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Mesocortical Anatomy and Plasticity
This continuation (years 17-20) describes experiments designed to investigate the structural organization of the mesocortices of the limbic lobe in the monkey and human brain. In its initial years, reinnervation of the amygdala was investigated and the term "plasticity" in the title has continued with the grant, although it is not longer descriptive of the research proposed. A central goal has been to investigate cortical association axons that link the association areas with the mesocortices. The reciprocal of this relationship has been investigated as well. In 1989 Alzheimer's disease research was added as a new direction since it targets the exact neurons that mediate this relationship. In the grant's last competitive review dual efforts relating to Alzheimer's disease research and nonhuman primate experimental neuroanatomical research were proposed, and the grant received a Javits Neuroscience Investigator Award. In this proposal, three new aims are outlined. Two deal with combined human and monkey investigations and aim to analyze Brodmann's areas 35 and 34. The former interconnects the entorhinal mesocortices with the temporal isocortices. Area 35 is understood poorly in the human brain and the first to develop neurofibrillary tangles in Alzheimer's disease. Monkey behavioral studies link it closely to associative memory. Area 34 forms the anterior and medial entorhinal cortex and contains laminar alterations in some brains of schizophrenics. It is damaged directly in all types of partial and traumatic herniation of medial temporal lobe through the incisura of the tentorium cerebelli. Cellular phenotypes and boundaries will be established for these areas, focusing both on projection and intrinsic neurons. An additional aim utilizes only the monkey and will assess "three neuron" neural systems related to the mesocortices. Specifically, the terminal fields of entorhinal neurons will be injected with a retrograde tracer and the labeled neurons will be filled intracellularly with Lucifer yellow to reveal their morphology. In the same preparation afferent axons projecting to characterized entorhinal neurons will be anterogradely labeled to establish their putative input patterns to the filled neuron. Confocal laser scanning microscopy will be used to analyze these preparations. For all aims, the data will provide baseline neuroscience information for cortical areas known to be involved in developmental, neurological and psychiatric disease. It is cost effective research that draws on a collection of non-human primate and human material gathered over the past 27 years at Harvard Medical School (1969-1978) and The University of Iowa (1979-present).
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0.958 |
1991 — 2000 |
Van Hoesen, Gary W |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Experimental Neuroanatomy of Systems Related to Cognition
This project is designed to investigate several novel aspects of the anatomical organization and pathology of the cerebral cortex which are directly relevant to cognitive functions. The issues addressed here follow directly on questions raised in other projects of this Program, especially on those pertaining to the neural basis of memory. The research is aimed at providing neuroanatomical characterizations of: (a) connectional links within specified cortical systems, and (b) the intrinsic structure of cortical regions participating in these systems. Such information is critical for the interpretation of experimental results based on any of the currently available approaches to the neurological basis of cognition in humans (e.g. the lesion method, PET, electrophysiology), and for the continued evaluation of theoretical formulations regarding the neural architecture and operations that may subserve cognition in primates. The proposal is divided into three subprojects: (1) high resolution tracing of connections from the parahippocampal cortex in monkeys, (2) topography of the human perforant pathway, and (3) modular organization of the human entorhinal cortex. Each subproject is based on a combination of modern histo- and immunocytochemical methods and conventional histology, to permit the dissection of chemically identified neurons and/or neurites. The information obtained from these tightly interrelated projects will contribute to a better understanding of the substrates of both normal and disordered human cognition at the cellular and connectional levels, and to a characterization of their alteration in conditions such as Alzheimer's disease.
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0.958 |
2002 — 2005 |
Van Hoesen, Gary W |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Experimental Neuroanatomy of Systems Related to Emotion
This project outlines an experimental neuroanatomical investigation on the monkey designed to assess the cortical and subcortical connectivity of the cingulate cortex. In close articulation with other components of the Program, the new effort represents a shift from our focus on the temporal lobe and issues pertaining to memory. We have set the stage for this shift with studies linking temporal structures to anterior cingulate cortices, and defining the interface between the posterior parahippocampal gyrus and the perisplenial cortices. In the forthcoming funding period we plan to carry out a number of studies aimed at elucidating, in greater detail than what is currently available, the connectivity of the cingulate cortex, a major function of which is the processing of emotion and feeling. These investigations will test the hypothesis that varied subdivisions of the cingulate cortex have distinct patterns of connectivity with subcortical an cortical structures. In fact, there is classic evidence that the primate cingulate cortex consists of cytoarchitectonically distinct subdivisions with other brain regions. This gap seriously limits the formulation of hypothesis in the study of cognition and emotion and the interpretation of current experimental results. Our aim is to bridge this gap by assessing the efferent and afferent connections of each cingulate subdivisions in the monkey using multiple injections of anterograde and retrograde tracers. Particular attention will be paid to subcortical connections since they have been sparsely studied in primates. Additionally, our data will reveal in detail the nature of intracingualte connectivity. The results of our proposed studies will provide a basis for understanding the neuroanatomical correlates of neurological conditions that have altered emotional states as salient clinical manifestations, and will aid in updating and extending theoretical formulations concerning the brain systems underlying complex cognition and behavior in humans, especially emotional processing and decision making. Our new direction is of direct relevance to other projects in the Program which deal with emotion, decision making and development (projects 1, 4 and 5).
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0.958 |