1994 — 1995 |
Sandell, Julie H |
R29Activity Code Description: Undocumented code - click on the grant title for more information. |
Anatomy of the Inner Nuclear Layer @ Boston University Medical Campus
neuroanatomy; retinal bipolar neuron; retina; amacrine cells; calcium binding protein; cell population study; neural information processing; glutamates; gamma aminobutyrate; protein kinase C; cone cell; rod cell; neural transmission; immunocytochemistry; human tissue; postmortem;
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0.958 |
1994 — 1998 |
Sandell, Julie |
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. |
Retinal Involvement in a Primate Model of Cerebrovascular Disease @ Boston University Medical Campus
This project will determine whether changes in the eye are correlated with visual impairment and cognitive decline in monkeys at known risk for cerebrovascular disease from hypertension and atherosclerosis. We will determine whether retinal changes such as microinfarction and hemorrhages indicate similar damage in the brain. In collaboration with Project 1, we will investigate the effect that such retinal pathology has on visual acuity and contrast sensititively. Clinical changes will be assessed at 6 weeks post-u[ (in short term animals) and followed for 12 or 48 months by color fundus photography and fluorescein angiography in the remaining animals. MRI scan of the vitreous following intravenous gadolinium infusion will provide a quantitative measure of the overall integrity of the blood-retina barrier at each examination interval. Anatomical experiments different types of damage. The functional, clinical and anatomical evaluation of the retina in this project will be correlated wit the cognitive, immunologic and neuropathologic changes detected in the same animals by the other projects. We will ask: 1) How are clinical changes in the retina correlated with the cognitive decline observed in the same animals? Is the animals's vision affected by these changes? Does observation of the retinal vasculature provide a "window" for changes that are occurring in the brain? 2) Are retinal ganglion cells injured by hypertension? Is this process exacerbated by an atherogenic diet? Do changes in synaptophysin labeling in the plexiform layers precede frank cell loss? 3) What effect do these two conditions have on the retinal interneurons and glia- the amacrine and Muller cells? Does the physical location of a cell or the fact that it has an axon affect the way it responds to the stresses imposed by these conditions? Do retinal glia (Muller cells) in damaged areas alter their expression of intermediated filaments or respond globally to damage? For all cell types local cell density will be determined using immunohistochemistry, and classic signs of cell damage will be documented. Clinical records will dictate the regions of the retinas we investigate in detail. In each retina, areas with different types of damage will be compared to undamaged areas. Clinical assessment of the fundus will be serial, so the same analysis can be performed on regions of the retina in which early signs of damage have disappeared by the time of sacrifice. Finally, the mechanisms that may protect the retina from temporary ischemia will be explored. Specifically, do retinal neurons responds to hypoxic stress by producing so-called "stress proteins" (e.g. the 72kD heat shock protein), or by activating "immediate early genes" (fos and jun)? Are specific growth factors induced in the retina in response to damage?
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1 |
2003 |
Sandell, Julie H |
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. |
Cortical Circuits Underlying Cognitive Functions @ Boston University Medical Campus
DESCRIPTION (adapted from applicant's abstract): The long term goal is to identify cortical circuits underlying cognitive functions. This endeavor requires the elucidation of the essential contributions that cerebral loci make to cognitive processes. The projects will concentrate on occipito-parietal (OP) & occipito-temporal (OT) contributions to visual perception and cognition of space, action and forms, and to memory. The specific aim of the proposed work is to test two interlinked hypotheses: 1) Each area within OP and OT cortices makes multiple, yet unique, combinations of essential contributions to perception, cognition and memory; 2) Permanent lesion-induced deactivations can be accompanied by neural compensations that attenuate and mask the magnitude of these contributions. Work will focus on cat middle and posterior suprasylvian cortices (areas 7, aMS, pMS, dPS, PSs and vPS), and the hypotheses will be tested by applying multi-site cooling deactivation (#1), or permanent lesion-induced deactivation (#2), to disrupt distinct combinations of a battery of specific visually guided behaviors. The data will be used to generate the first comprehensive compendium of the multiple and characteristic combinations of neural contributions each of the constituent areas in OP and OT cortices make to different aspects of perception, cognition and the memory. The compendium will highlight similarities, overlap, differences, lateralization, uniqueness and nested hierarchy of contributions areas make to cognitive and higher brain functions. The compendium is a requisite for accurately identifying and interpreting neural compensations that may emerge following cerebral lesions. Together, the acquired knowledge is essential for the future development of biologically-realistic, functionally-based models of cerebral operations. Moreover, the knowledge will: 1) form the foundation of future studies of emergent and higher-order integrative processes; and 2) guide future investigative studies on defective cerebral systems that underlie diminished cognitive function, agnosia, and visual neglect and other sequelae of damage of visuoparietal and visuotemporal regions.
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0.958 |
2004 |
Sandell, Julie H |
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. |
Cognition After Lesions of Immature Cerebral Cortex @ Boston University Medical Campus
DESCRIPTION (Provided by applicant): Brain lesions incurred early in life produce a different brain from that reached after normal development. The lesion-induced modifications are specific & ordered and they contribute to sparing of cognitive processes that are severely handicapped by equivalent lesions incurred by the mature brain. The long-term goal is to identify classes of spared functions and the structures contributing to them. The specific aim of the proposed work is to test the two component hypothesis that: 1) cognitive functions are spared by early lesions of areas 17 & 18, & 2) the contributions to cognition made by middle suprasylvian (MS) cortex, in the parietal region, and by ventral posterior suprasylvian (vPS) cortex, in the temporal region, differ from contributions the same regions make to cognition & behavior in the intact brain. Normally these two regions make clearly discriminable, and non-overlapping, contributions to cognition of space & action, and to learning, memory & recognition of forms. Studies will be carried out on mature cats that incurred damage of areas 17 & 18 on P1, P28, and in adulthood (P180), and normative data will be collected from intact cats. After extensive training on a battery of behavioral tasks designed to define the magnitude of the cognitive sparing, cooling loops will be implanted to temporarily deactivate MS or vPS cortices and assess the contributions the two regions make to the spectrum of spared functions. The behavioral tasks will reveal: 1) classes of spared cognitive functions; 2) age dependent differences in sparing; 3) whether remaining MS & vPS regions adopt functions normally associated with areas 17 & 18; & 4) whether functions normally localized to either MS or vPS cortices become dispersed, as substantial rewirings suggest. The work will provide detailed information on the capacities of the immature cerebral cortex to compensate for cognitive functions severely handicapped following equivalent damage of the mature cerebrum. The identification of these capacities is important for comprehending the spectrum of consequences of early cerebral cortical damage, and for developing therapeutic strategies that attempt to enhance the sparing of cognitive functions.
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0.958 |