1985 |
Price, Joseph L |
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. |
The Olfactory Cortex
The structure, organization and development of the olfactory system will be studied with a variety of normal and experimental methods, including the autoradiographic method and horseradish peroxidase method of demonstrating axonal connections, as well as the electron microscope. Most of the projects are directed at the olfactory cortex of the rat including analyses of the organization of the axonal projection to this cortex from the olfactory bulb, the organization of the association and commissural fibers within the cortex, and the cells of origin of extrinsic projections to other parts of the brain. In addition, the development of the afferent connections will be analyzed by studying the effect of partial lesions of the olfactory bulb at the time of birth, and by following the electrophysiological responses of the cortex during the first two weeks following birth. In addition the efferent connections of the several cytoarchitectonic areas within the prefrontal cortex of the rat and cat will be studied, with emphasis on the areas which have been previously defined as receiving projections from the olfactory cortex or amygdala.
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1987 — 2008 |
Price, Joseph L |
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. |
Studies On the Olfactory Cortex
This project will build on the very considerable progress that has been made in the past grant period in the analysis of the organization of the orbital and medial prefrontal cortex (OMPFC), and the thalamic and limbic areas that are connected with it. The OMPFC has been implicated in several important functions, including stimulus reward associations and the control of goal-directed behavior, but little has been known about the neural organization that might underlie such functions. In the previous grant period 24 architectonic areas were defined in the OMPFC, and sensory and limbic inputs to these areas were demonstrated, largely with retrograde axonal tracers. Three largely distinct networks of connections within the OMPFC were defined. In the next period anterograde axonal tracers will be used to continue the analysis of corticocortical connections within the OMPFC. Special emphasis will be placed on the termination of convergent inputs to architectonic areas in the central and rostral orbital cortex, and on laminar patterns of termination of feed-forward and feed-back connections. In addition, connections of the OMPFC with the hypothalamus and brainstem will be defined in order to clarify the control exerted by the OMPFC over visceral function. connections between the OMPFC and thalamic nuclei other than MD (e.g. the anteromedial and ventral anterior nuclei) will be defined with anterograde and retrograde axonal tracers. In most cases injections of at least four tracers will be made in each experiment, in order to obtain direct comparison of several different projections. The correlation between cortical areas in rats and monkeys will also be studied, with an analysis of cortico-cortical connections within the OMPFC of rats. In order to visualize the complex patterns of connections within the prefrontal cortex, computer methods will be developed to make 3-D reconstructions of the frontal cortex from plots of labeled cells and axons in serial sections. From these reconstructions unfolded 2-D maps of the cortex will be produced, in order to provide direct visualization of patterns of connections within the cortex, and serve as a reference to the 3-D reconstruction for quantitative and statistical analysis of labeling patterns. In addition, the OMPFC of the human brain will be analyzed with several histological and immunohistochemical stains, in order to define architectonic areas and correlate these with the areas previously distinguished in monkeys. This is especially significant because of the increasing use of imaging methods to analyze patterns of activity within the human brain, and the need to correlate these patterns with the architectonic structure of the cortex and with connections that have been defined in non-human primates.
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1989 — 2002 |
Price, Joseph L |
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. |
Olfactory Cortex
The proposed project will build on the progress that has been made during the past grant periods in the analysis of connectional networks that link architectonic areas of the orbital and medial prefrontal cortex (OMPFC) in monkeys. The areas within these orbital and medial networks have differential connections both with other cortical areas and with subcortical structures such as the thalamus, amygdala, hypothalamus and periaqueductal gray. In humans, positron emission tomography (PET) studies indicate that the areas of the OMPFC have abnormal levels of activity in psychiatric disorders such as unipolar and bipolar depression. In the next grant period the further connections of the networks of the OMPFC with cortical areas in the dorsolateral PFC and the temporal cortex will be defined in monkeys with anterograde axonal tracers injections into the target structures. Connections from the medial and orbital networks to the striatum will also be defined in the same experiments, and in experiments with retrograde axonal tracers injected into the accumbens and caudate nuclei and the putamen. In order to correlate the observations in monkeys with imaging studies in humans, the architectonic areas that have been identified in monkeys will be defined in human brains, using the multiple staining methods that were used in monkeys. The monkey and human maps will be further correlated with the aid of computer generated unfolded maps of the frontal lobe. The role of the human OMPFC in clinical depression will be further studied in two projects. In the first, autopsy brain tissue from control subjects or from subjects diagnosed with unipolar or bipolar depression or schizophrenia will be studies to determine cortical volume and cell number in the defined architectonic areas in the subgenual or medical orbital cortex. In the second, architectonic areas will be outlined on MRI images of brains from depressed or control suects that were previously studied with PET. By correlating the PET and MRI images, levels of metabolic and synaptic activity can be determined within the defined architectonic areas as a function of unipolar or bipolar depression.
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1997 — 1998 |
Price, Joseph L |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Olfactory Cortex Structure &Function
structural biology; mental disorders; nervous system; biomedical resource; Mammalia;
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0.961 |
1999 — 2002 |
Price, Joseph L |
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. |
Mapping of Neuropathology in Healthy Aging and Dementia
This project is closely related to the overall research goal of this program project, namely to define the behavioral and biomedical correlates of the clinical course of a defined group of subjects with SDAT (or in this project, with neuropathologically proven Alzheimer's disease) in comparison with the course of healthy aging in non-demented subjects. The specific goals of the project can be expressed as two questions (1) What pattern of pathology is characteristic of the earliest stage of Alzheimer's disease? (2) what is the relationship between the patterns of tangles and placques seen in healthy aging and in the earliest, very mild stage of dementia? To address these questions, the distribution and density of neurofibrillary tangles, amyloid placques and related immunohistochemical markers (e.g. with antibodies counted in serial sections cut through the ventral forebrain from a range of carefully assessed non-demented and demented elderly cases. The presence or level of dementia in these cases will be determined in the clinical core, either by pre-mortem assessment , or by a retrospective, post-mortem interview with a closely related collateral source (usually a spouse or adult child). Because results from the previous grant period indicate that he earliest pathological changes related to Alzheimer's disease must be found in cases that have not yet shown any clinically detectable dementing change, emphasis will be placed on very old non-demented cases. In these cases special attention will be given to small patches of "primitive" or "diffuse" placques in the temporal or orbital neocortex that were identified in non-demented cases during the previous grant period, and which may represent the earliest deposition of amyloid. To examine a possible link between early plaque and tangle formation, immunohistochemistry with antibodies against tau and related proteins (e.g. the antibody Alz-50) will be used to stain the region of plaques for altered neurites ("neuropil threads") that might represent an early neurotoxic reaction to amyloid deposition.
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