1996 — 2000 |
Wozniak, David |
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. |
Glutamate Receptors, Memory and Long Term Potentiation
It has been shown repeatedly that antagonists of the NMDA subtype of glutamate receptor interfere with performance on learning/memory tasks and also block the induction of hippocampal long term potentiation (LTP). It is generally believed, but without directly supporting evidence, that the ability of NMDA antagonists to block hippocampal LTP induction underlies the apparent memory impairing actions of these compounds. However, in view of the applicants' finding that NMDA antagonists, at subcutaneous doses which do not have damaging effects on hippocampal neurons, cause acute pathomorphological changes in posterior cingulate neurons, the question arises whether the impaired learning/memory performance associated with these compounds might relate more to their brain damaging action in the cingulate cortex than to postulated interference in hippocampal LTP. The applicants have shown that anticholinergic drugs prevent the cingulate neurotoxic side effects of NMDA antagonists, and they have developed preliminary evidence that anticholinergic drugs may also counteract the impaired acquisition performance induced by NMDA antagonists. In the present Project, these preliminary findings will be further explored and, as in our previous work, we will systematically investigate the role that nonassociative factors such as sensorimotor disturbances may play in affecting performance on our learning/memory measures. In another series of experiments, we will administer high doses of the NMDA receptor antagonist MK-801 to rats in order to create extensive bilateral necrosis in the posterior cingulate/retrosplenial cortices, and the rats will be tested behavioraIly to determine if this treatment impairs learning/memory or other behavioral functions. In this Project we will also conduct electrophysiologic studies that are parallel to our behavioral work in that they will focus on whether anticholinergic drugs prevent NMDA antagonists from blocking the induction of hippocmpal LTP. In addition, we will attempt to induce LTP in the in vivo cingulate cortex and, if successful, we will determine whether MK-801 blocks cingulate LTP and whether anticholinergic agents prevent MK-801 from blocking cingulate LTP. It is expected that these experiments may help clarify the locus of action and mechanism by which NMDA antagonists may impair learning/memory performance while also clarifying what role, if any, either hippocampal or cingulate LTP plays in the apparent memory disrupting process.
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1 |
2011 — 2013 |
Wozniak, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Neuroimaging and Hormonal Analyses of Gender and Interindividual Differences in Competitive Choices @ Eastern Michigan University
Previous work has shown significant gender differences in the likelihoood to compete, with men being about twice as willing as women. More recent work suggests that these differences are driven by hormonal levels within an individual over time. This proposal will assess the relationship between hormones and both competitive and cooperative choices in a larger sample of men and women. Estrogen, progesterone (in women) and testosterone (in men and women) will be measured. A second study will add neuroimaging to test the hypothesis that gender and individual differences in competitive/cooperative choices result from hormonal modulation of activity in the brain's reward areas.
In terms of broader impacts, the results showing that men are more willing to compete than women have been and have been offered as a partial explanation for gender differences in outcomes in earnings and careers, including the scarcity of women in top executive and academic positions. This research will shed light on the causes of this result, and will help to evaluate the desirability and design of policy interventions to address such differences. A better understanding of the reasons for the wide variations in competitive behavior can also help individuals make more informed decisions about education and careers on their own as well.
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0.94 |
2015 — 2019 |
Wozniak, David Francis |
U54Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These differ from program project in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes, with funding component staff helping to identify appropriate priority needs. |
Core C - Model Systems Core
Model Systems Core Project Summary Animal models are revolutionizing our understanding of IDDs, and such models provide fundamental insights into biological pathways and often display phenotypes that are similar to clinical indicators of the human disease, providing an opportunity to deduce mechanisms of disease pathology, and also to develop therapies. The Model Systems Core (MSC) is organized into three units ? the Animal Behavior Unit, the Neuropathology Unit, and the Functional Assessments Unit. The goal of the MSC is to provide expertise, resources, and assessment to Center investigators involved in the creation and evaluation of animal and cellular models relevant to IDD, drawing on strengths in genetics, brain imaging, bioinformatics, and neuroscience to provide advice, assistance, and services to investigators at all career stages. The specific aims are: 1) Provide consultation to investigators needing assessments in animal behavior, pathology and CNS function. A priority for the Core Directors and Unit leaders is to make certain that first-time users are guided to appropriate services and understand the complement of available resources; 2) Characterize neurological deficits in rodent and cellular models of IDD submitted by investigators. The MSC is configured to provide access to a range of experimental approaches including: i) functional phenotyping of mice and rats (learning and memory, motor/sensorimotor functions, alterations in emotionality/motivation, social interactions, sensory behavioral functions, depression-like behaviors, and behaviors related to models of Autism Spectrum Disorder; ii) histological services to evaluate IDD-related changes at the cellular level; and, iii) sophisticated, non- invasive imaging (MRI, functional connectivity optical imaging) as well as in vitro (including advanced microscopy of cellular models) and in vivo neurophysiological assessments, such as electroencephalography (EEG), polysomnography, and somatosensory evoked potentials in animal models of IDD; 3) Assess novel therapies and/or biomarkers in models of IDD in animal behavior, pathology and CNS function. Each Unit within the MSC is already configured to allow rapid, sensitive testing of novel therapies and/or biomarkers for IDD models; 4) Integrate information across units, cores and other existing facilities within the University. Together with the Unit leaders, MSC Directors will provide guidance for institutional resources both within and outside of the MSC. Together with the Scientific Advisory Panel, MSC Directors will also help investigators identify the best model system for a specific gene locus, clinical phenotype and/or screening for compounds to reverse disrupted function. WUSTL has state-of-the-art expertise and facilities for zebrafish, C. elegans, and/or Drosophila models of human disease.
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0.958 |
2020 — 2021 |
Wozniak, David Francis |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Model Systems Core
Model Systems Core Project Summary/Abstract The Model Systems Core (MSC) will leverage the institutional strengths of Washington University School of Medicine (WUSM) in genetics, neuroscience, bioinformatics and neuroimaging to address key questions on the causes and treatments of IDD with particular reference to genetic abnormalities and environmental factors. The MSC will be organized into two units ? the Cellular Models Unit (CMU) and the Animal Assessments Unit (AAU), the latter being composed of three subunits including Animal Behavior, Neuropathology, and Neurophysiology. Through its team of interactive scientists, the MSC will pursue its specific aims by providing seamless expertise, resources, and assessments to committed WUSM investigators for the purpose of: (1) promoting the discovery of the basic molecular and cellular pathways shared by diverse causes of IDD; (2) determining the neural signatures associated with IDD at the neural circuit level and whole brain; (3) characterizing core neurobehavioral features of IDD and clarifying their causal origins; and (4) developing interventions to ameliorate the effects of genetic or environmental insults on the developing brain. To achieve these goals, the MSC will use an integrated model systems approach to synergize the strengths of its own units as well as those of the Clinical Translational Core and the Developmental Neuroimaging Core. Additional aims for each unit will also be operative. For example, reprogrammed somatic cell models of human disorders provide fundamental insights into biological pathways as well as disease processes; therefore, the MSC will now offer renewable patient-derived human IDD cellular models to link genetic alterations with disease mechanisms and phenotype via the CMU. The MSC will also continue to provide consultation and comprehensive assessment of brain structure, pathology, physiology and behavior of IDD animal models through the AAU. Reaching across cores, the CMU will work closely with the Clinical Translation Core?s human genomic characterization unit to develop IDD patient registries that will be directly used as a recruitment source for derivation of patient-derived cellular models. Similarly, the AAU depends upon the Developmental Neuroimaging Core for imaging relevant preclinical models to investigate mechanisms underlying developmental pathology potentially providing a bridge to clinical studies. Using these strategies, the overarching mission of the MSC is to identify new treatments, biomarkers and/or interventions that can prevent or reduce the impact of IDD-linked diseases. As more genomic data becomes available and WU investigators capitalize on this information, another critical role for the MSC will be the integration of new and existing information across the IDDRC@WUSTL cores and other existing facilities within the University.
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0.958 |