1985 — 1989 |
Peters, Alan |
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. |
Aging and the Nervous System @ Boston University Medical Campus
The general objective of this program project is to examine behavioral, anatomical and biochemical changes that occur during normal aging of the nervous system of mammals, and the potential of the aging nervous system to compensate for these changes. To accomplish these goals, a number of systems are being examined. In the auditory system the effect of age on the ability of rats to acquire and maintain auditory discrimination are being studied, and this ability is being correlated with morphological age changes in the cochleas, cochlear nuclei and spiral ganglion. The morphological changes include examination of the loss of receptor cells, changes in synapses between neurons, and accumulation of pigment. More centrally, the ability of neurons in the auditory cortex to respond to deafferentation at varying ages are being examined to determine if loss of the callosal input results in compensatory growth of afferents entering the cortex from the thalamus. In the olfactory system changes in the receptor cells, the morphology of neurons and their synaptic input are being studied as rats age. These studies will also indicate if the aging nervous system still exhibits plasticity, and collateral sprouting of axons is being further studied in the dentate gyrus. A possible important factor in the aging of neurons is the state of the microvascular network, and this is being examined both biochemically and anatomically. Additional biochemical studies are being carried out on nuclear chromatin, with which the effects of age are being assessed by determining the susceptibility of chromatin to cleavage by bacterial nuclease.
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0.957 |
1985 — 1987 |
Peters, Alan |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Research Training in Neuroanatomy @ Boston University Medical Campus |
0.957 |
1985 — 1996 |
Peters, Alan |
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. |
Structure and Organization of the Cerebral Cortex @ Boston University Medical Campus
Continued support is requested to examine the morphology, synaptic relationships, immunocytochemistry, and physiological response properties of neurons in the cerebral cortex of rat, cat and monkey. The goal is to obtain information about the neuronal circuits in the cerebral cortex. A Golgi-EM technique will be used to examine individual neurons. Thus, their forms will be determined with the light microscope, and their cytological characteristics and synaptic relationships with the electron microscope. This study will include a determination of the types and distribution of synapses formed by the axons of the neurons. When the study of neurons in rat visual cortex is completed, the neuronal composition of that cortex can be determined. Through immunocytochemistry the distribution and identity of glutamate decarboxylase, substance P and vasoactive intestinal polypeptide (VIP) positive components in the cortex will be evaluated. Some of the extrinsic connections of cortical neurons will also be investigated, with particular attention being paid to the connections between area 17 and the peristriate areas, and the callosal connections of these latter areas in rat cortex. This data will be correlated with the results obtained from intracellular recordings taken from neurons in area 18 contained in brain slice preparations. The neurons will be activated by electrical stimulation of the callosal and intracortical connections and they will be identified by intracellular injections of markers. Blocking inhibitory synapses and applying neurotransmitters to the preparation will allow us to assess the role that intrinsic neurons might have in modifying the responses of these neurons.
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0.957 |
1986 — 1988 |
Peters, Alan |
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. |
Aging and the Primate Nervous System @ Boston University Medical Campus
The general objective of this program project is to examine behavioral, anatomical and biochemical changes that occur during normal aging of the nervous system of mammals, and the potential of the aging nervous system to compensate for these changes. To accomplish these goals, a number of systems are being examined. In the auditory system the effect of age on the ability of rats to acquire and maintain auditory discrimination are being studied, and this ability is being correlated with morphological age changes in the cochleas, cochlear nuclei and spiral ganglion. The morphological changes include examination of the loss of receptor cells, changes in synapses between neurons, and accumulation of pigment. More centrally, the ability of neurons in the auditory cortex to respond to deafferentation at varying ages are being examined to determine if loss of the callosal input results in compensatory growth of afferents entering the cortex from the thalamus. In the olfactory system changes in the receptor cells, the morphology of neurons and their synaptic input are being studied as rats age. These studies will also indicate if the aging nervous system still exhibits plasticity, and collateral sprouting of axons is being further studied in the dentate gyrus. A possible important factor in the aging of neurons is the state of the microvascular network, and this is being examined both biochemically and anatomically. Additional biochemical studies are being carried out on nuclear chromatin, with which the effects of age are being assessed by determining the susceptibility of chromatin to cleavage by bacterial nuclease.
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0.957 |
1988 |
Peters, Alan |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Neuroanatomy @ Boston University Medical Campus |
0.957 |
1990 — 1999 |
Peters, Alan |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Research Training in Structural Basis of Neurobiology @ Boston University Medical Campus |
0.957 |
1991 — 1993 |
Peters, Alan |
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. |
Neural Substrates of Cognitive Decline in Aging Monkeys @ Boston University Medical Campus
Our previous work has demonstrated that aged monkeys show cognitive loss and accumulation of amyloid and senile plaques in the cerebral cortex similar to changes observed in normal human aging. However monkeys do not show neurofibrillary tangles and there is no major loss of cortical projection neurons in areas so far examined (primary visual and motor cortex, the subiculum of the hippocampal formation). There is cell loss in subcortical sites, including the cholinergic nucleus basalis, and, based upon other studies, there is likely to be cell loss in other subcortical nuclei that provide neurochemically specific afferent input to the cerebral cortex. In addition, we have observed degeneration in intracortical and subcortical white matter and in cortical neuropil that may reflect loss of synaptic input, while other data suggest changes in levels of neurotransmitters and their processing enzymes as well as related receptors. Finally the amyloid proteins in monkey brain are identical to those in human brain. It is not known whether they are the result of direct age-related pathogenic factors or a result of changes in free radical metabolism. The similarity of these behavioral and neurobiological changes with those observed in humans form a basis for our proposed investigation of age-related changes in rhesus monkeys. The overall hypothesis of this project is that cortical pathology underlines the cognitive decline seen in aging monkeys to man. To investigate this hypothesis we propose the following specific aims. We will behaviorally test monkeys that range in age from young adults (5 yrs) to the very elderly (25+ yrs) to assess memory and executive function, and since it is likely that these two cognitive domains are localized primarily in frontal lobe association cortex and the temporal lobe system, respectively, we will examine these areas in detain in a number of ways. We will look for changes in the neuronal population, and especially in the inhibitory neuronal types, and also for loss of synapses, and alteration in glial cells and changes in neurotransmitter levels, metabolism and receptors and the maturation states and distribution of plaques. We will also correlate the changes in neurochemically specific nuclei with cognitive changes of individual monkeys and their cortical pathology since these nuclei provide inputs to the cerebral cortex. To identify pathogenic factors we also assess free radical metabolism and its relationship to alterations in mechanisms of amyloid accumulation. These data will allow us to identify the time of onset and the sequence of structural and metabolic alterations that underlie age-related cognitive decline. We expect these data to provide the basis for a suitable primate model of normal human aging that can eventually be used for evaluation of potential therapeutic intervention.
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0.957 |
1994 — 1995 |
Peters, Alan |
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. |
Neural Substrates of Cognitive Decline @ Boston University Medical Campus
Our previous work has demonstrated that aged monkeys show cognitive loss and accumulation of amyloid and senile plaques in the cerebral cortex similar to changes observed in normal human aging. However monkeys do not show neurofibrillary tangles and there is no major loss of cortical projection neurons in areas so far examined (primary visual and motor cortex, the subiculum of the hippocampal formation). There is cell loss in subcortical sites, including the cholinergic nucleus basalis, and, based upon other studies, there is likely to be cell loss in other subcortical nuclei that provide neurochemically specific afferent input to the cerebral cortex. In addition, we have observed degeneration in intracortical and subcortical white matter and in cortical neuropil that may reflect loss of synaptic input, while other data suggest changes in levels of neurotransmitters and their processing enzymes as well as related receptors. Finally the amyloid proteins in monkey brain are identical to those in human brain. It is not known whether they are the result of direct age-related pathogenic factors or a result of changes in free radical metabolism. The similarity of these behavioral and neurobiological changes with those observed in humans form a basis for our proposed investigation of age-related changes in rhesus monkeys. The overall hypothesis of this project is that cortical pathology underlines the cognitive decline seen in aging monkeys to man. To investigate this hypothesis we propose the following specific aims. We will behaviorally test monkeys that range in age from young adults (5 yrs) to the very elderly (25+ yrs) to assess memory and executive function, and since it is likely that these two cognitive domains are localized primarily in frontal lobe association cortex and the temporal lobe system, respectively, we will examine these areas in detain in a number of ways. We will look for changes in the neuronal population, and especially in the inhibitory neuronal types, and also for loss of synapses, and alteration in glial cells and changes in neurotransmitter levels, metabolism and receptors and the maturation states and distribution of plaques. We will also correlate the changes in neurochemically specific nuclei with cognitive changes of individual monkeys and their cortical pathology since these nuclei provide inputs to the cerebral cortex. To identify pathogenic factors we also assess free radical metabolism and its relationship to alterations in mechanisms of amyloid accumulation. These data will allow us to identify the time of onset and the sequence of structural and metabolic alterations that underlie age-related cognitive decline. We expect these data to provide the basis for a suitable primate model of normal human aging that can eventually be used for evaluation of potential therapeutic intervention.
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0.957 |
1997 — 1999 |
Peters, Alan |
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. |
Myelin @ Boston University Medical Campus
During the last grant period we examined several areas of the cerebral cortex of young (4 to 6 years of age) and old (over 25 years of age) rhesus monkeys and came to the conclusion that there is no significant loss of cortical neurons with age. However there are other significant changes both in the cortex and in the underlying white matter. The most obvious of these is a breakdown in the integrity of myelin. This is not demyelination in the sense that the axons are left bare, but a breakdown in the integrity of the sheats that might best be termed ~dysmyelination~. There is some evidence of axonal degeneration, but this is not pronounced in the cortex. Furthermore, in our study of the frontal cortex we found that there is a correlation between the extent of myelin breakdown and the performance of old monkeys on the delayed nonmatching to sample tasks. In addition, MCI scans of the cerebral hemispheres of our monkeys, show a loss of white matter, but not of gray matter, with age. And when the extent of loss of white matter is plotted against the behavioral performance of the monkeys, there is a significant correlation with the performance of the monkeys on the acquisition component of the delayed nonmatching to sample task. These results have lead us to believe that a breakdown in the integrity of myelin might underlie the cognitive deficits, since this would reduce the conduction rates along some axons and disrupt the timing of synaptic activity in neuronal circuits. Obviously, an in depth study of the effect of aging on myelin is important. We propose to continue MCI scans to obtain better data on the correlation between white matter loss and behavioral performance. In addition, we will use a new tritium quenching technique to determine whether myelin loss is more prevalent in some cortical areas that in others, and will correlate the results with the recorded behavior of the monkeys. Finally, we propose to examine the effect of aging on myelin sheaths by electron microscopy, to determine how sheaths break down, what size fibers are most affected, and whether the breakdown of the myelin occurs equally throughout the CNS, or whether it is more prominent in some fiber pathways than in others. For this purpose, we have chosen to examine the visual pathway, since this system offers a hierarchical system of fiber connections, as well as intracortical and extracortical connections, whose origins and terminations are well known.
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0.957 |
2000 — 2011 |
Peters, Alan |
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. |
Structural Studies in the Central Nervous System @ Boston University Medical Campus
In this resubmission, Project 5 of the original proposal has been deleted, but the study of the age-related changes in layer 1 of cerebral cortex has been retained and is now included in this Project. This Project will define the structural changes that occur with age in the central nervous system. By using middle aged monkeys we will determine when these changes first occur, and because all monkeys are behaviorally tested, we will relate structural changes to cognition. The study of layer 1 is retained because we have found that the age-related thinning and the loss of synapses from layer 1 is the most obvious change in the cortex, and in area 46 we have shown that these changes correlate with both age and cognitive decline. We need to know if these changes are ubiquitous, and so we propose to examine layer 1 in entorhinal cortex and in area 17 to ascertain if age produces similar changes in these cortices and if they also correlate with cognitive decline. We need to know if these changes are ubiquitous, and so we propose to examine layer 1 in entorhinal cortex in area 17 to ascertain if age produces similar changes in these cortices and if they also correlate with cognitive decline. Another major goal is to further pursue the breakdown of myelin sheaths we have shown to occur with age: we believe that this breakdown brings about cognitive decline through alterations in conduction rates, affecting timing in neuronal circuits. The two model systems we have chosen to examine myelin breakdown brings about cognitive decline through alterations in conduction rates, affecting timing in neuronal circuits.. The two model systems we have chosen to examine myelin sheaths, nerve fiber loss, and active phagocytosis undertaken by both astrocytes and microglial cells. We will also examine the splenium of the corpus callosum, the vertical nerve fiber bundles in area 46, the optic radiations, and the fornix, for additional information about age-related nerve fiber changes and loss with age. Our data on the myelin breakdown in the cerebral cortex and the splenium will be correlated state of the myelin sheaths whose composition is being examined in Project 2. Another aim is to use antibodies to label microglial cells and oligodendrocytes to determine how these neuroglial types respond to age changes in white matter. We will determine when microglial cells first become activated and whether some fiber pathways are more affected than others. For oligodendrocytes, it is intended to determine if they increase in frequency with age, in response to the breakdown of their myelin sheaths.
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0.957 |
2008 — 2010 |
Fisher, Peter (co-PI) [⬀] Peters, Alan Funderburg, Richard |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: the Impact of State and Local Taxes On Growth Using Improved Tax Measures
This research will provide important new evidence on a long-standing controversy in academic and public policy circles: whether tax incentives are a cost-effective means of stimulating state economic growth. Previous research has relied on statistical analysis to determine the effect of state and local taxes on state economic growth, controlling for other factors that influence growth. This project will utilize a superior measure of the crucial explanatory variable -- state and local taxes on business -- and test the sensitivity of the results to the kind of tax measure used. Most previous estimates of business taxes' influence on growth have employed a broad, average tax measure such as state taxes as a percent of state personal income. Yet, economic theory suggests that marginal costs, not average costs, are what matters for profit-maximizing investment behavior. This project develops and uses a marginal tax rate -- the additional taxes resulting from new business investment in a state -- derived from a representative firm model that incorporates apportionment formulas, state and local tax incentives, and other features of the state and local tax system. Marginal tax rates are in fact very poorly related to the kinds of average tax rates typically employed in previous studies. This casts doubt on the accuracy of prior estimates of the size of the tax effect on growth in cross-state evaluations of economic development policy. To investigate the possible bias, the researchers will estimate multiple growth equations for 20 U.S. states using alternative tax measures and a variety of functional forms.
Something of a consensus has developed among academic researchers over the past 15 years that the sensitivity of economic growth to business taxes is small (although some academics take issue with this conclusion). This in turn implies that tax incentives do not stimulate sufficient growth to offset the public revenue losses from the incentives. Incentives are good policy, then, only if the public benefits exceed the tax losses. Public economic development officials, on the other hand, continue to believe that incentives not only create jobs but augment revenue. This project helps to refocus scholarly debate on replicable findings about the impact of state and local business taxes on economic growth. Because the marginal business tax measures in this project differ considerably from the commonly used measures, this research will shed important light on this debate.
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0.976 |