1985 — 1987 |
Rhoades, Robert 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. |
Collicular Development in Hamster @ Univ of Med/Dent Nj-Sch Osteopathic Med
The first goal of the experiments described in this application is to delineate the extent to which the collicular visual and somatosensory representations follow interdependent developmental programs. The second aim is to determine whether or not the laminar and topographic organizations of tectal sensory inputs affect the development of efferent projections from this nucleus. To accomplish our first goal, we will examine the normal ontogeny of the visual and somatosensory representations with extracellular single unit recording methods. We will also experimentally alter either the visual or somatosensory map by means of neonatal surgery and determine whether or not this produces a concomitant change in the collicular representation we have not directly manipulated. Extracellular single unit recording and receptive field mapping techniques will again be employed to assess the consequences of our experimental intervention in the normal development of these animals. We will also determine the effects of altered sensory organization upon the ontogeny of three tectofugal pathways which we have described in detail in normal adult hamsters (see below for references). These are the tectospinal projection, the intercollicular pathway, and the collicular projection to the lateral posterior nucleus. These projections arise from neurons which have clearly different laminar distributions, and functional and morphological characteristics. We will use multiple retrograde axonal tracing methods to determine: (a) whether or not these distinct projections are achieved by the elimination of axon collaterals in neurons which project to multiple targets for a limited period during infancy, and (b) whether or not alterations in the laminar or topographic organization of sensory inputs change the distribution of neurons contributing axons to a given tectofugal pathway.
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0.918 |
1985 — 1994 |
Rhoades, Robert 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. 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. |
Trigeminal Primary Afferent Organization and Development @ University of Toledo Health Sci Campus
The experiments that comprise this application test the hypothesis that distinct subsets of primary afferent neurons respond differently to transection of a peripheral nerve in early postnatal life. Peripheral nerve damage in a newborn produces a number of changes in the primary afferent innervation of the periphery and the spinal cord and/or brainstem. These include the death of some axotomized ganglion cells and axonal regeneration (either accurately or inaccurately) by others, peripheral and central collateral sprouting by undamaged primary afferents, and reorganization of the projections of both damaged and undamaged axons at the level of the ganglion. Primary afferent neurons can be distinguished by a variety of markers including birthdate, peptide phenotype, the presence of different cell surface antigens, and binding of different lectins. We will use several such markers to define the effects of neonatal transection of the rat's infraorbital nerve (ION) upon 4 distinct subsets of trigeminal (V) ganglion cells: those that synthesize substance P, those that synthesize somatostatin, those that bind the lectin Bandeiraea simplicifolia-I (BS-I), and those that are recognized by the monoclonal antibody RT97, a marker for neurofilament [3H]-thymidine labelling. We will use these markers in conjunction with retrograde tracing, sequential multiple labelling, and intracellular recording and tracer injection to determine the extent to which members of each of the cell classes listed above: 1) die as a result of neonatal axotomy, 2) regenerate accurately to the periphery after such damage, 3) engage in peripheral collateral sprouting after injury to other V axons, and 4) reorganize their peripheral projections at the level of the V ganglion after damage to their own axons or those of other V primary afferents. In a final series of experiments, we will evaluate the role that nerve growth factor may play in accuracy of regeneration of damaged axons and peripheral collateral sprouting by undamaged fibers by depriving rats of NGF after neonatal ION transection. Information about the extent to which distinct subclasses nerve damage may ultimately permit independent modulation of each of these types of reorganization.
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0.918 |
1987 |
Rhoades, Robert W |
S15Activity Code Description: Undocumented code - click on the grant title for more information. |
Zeiss Photomicroscope @ Univ of Med/Dent Nj-Sch Osteopathic Med
photomicrography; biomedical equipment resource;
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0.918 |
1987 — 1988 |
Rhoades, Robert 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. |
Damage Induced Trigeminal Reorganization @ Univ of Med/Dent Nj-R W Johnson Med Sch |
0.907 |
1988 — 1991 |
Rhoades, Robert 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. |
Collicular Development @ University of Toledo Health Sci Campus
The goal of the research proposed is to understand, at the level of individual cells and fibers, the substrate of the functional reorganization that follows neonatal deafferentation of the hamster's superior colliculus (SC). The particular experiments outlined in this application are designed to examine three aspects of the collicular reorganization that occurs after neonatal enucleation of one eye. These are: 1. Reorganization of the axon arbors of individual, functionally characterized retinal and subcortical somatosensory afferents, 2. Effects of deafferentation upon structure-function relationships for postsynaptic cells, and 3. The role which sprouting of noradrenergic (NA) afferents plays in deafferentation induced functional reorganization. Extracellular recording studies have already shown that neonatal enucleation markedly alters the response properties of many SC neurons and "bulk tracing" experiments have demonstrated further that part of this reorganization might be explained by alterations in the terminal fields of several of the residual projections to the tectum. We will use intra-axonal recording and horseradish peroxidase (HRP) injection techniques to determine whether the expansion of the remaining retinal and subcortical somatosensory inputs to the SC reflects collateral sprouting; i.e., increases in the arbors of individual axons, "spreading" of azon terminals, i.e., an increase in the extent of the terminal arbors of a given axon will a concomitant decrease in their density or reduced overlap of normally sized arbors from different axons. We will also employ intracellular recording and HRP injection to define the receptive fields and structure of postsynaptic cells in the deafferented SC. A number of morphological studies have suggested that changes in the dendritic architecture of partially deafferented neurons may also play an important role in functional reorganization. Our experiments will test this hypothesis directly at the level of individual cells. In a third set of experiments, we will examine the role that sprouting of NA axons plays in the physiological changes observed in the deafferented SC. Our previous studies have demonstrated that NA fibers sprout vigorously after neonatal enucleation and our working hypothesis is that these afferents may act to inhibit the expression of weak sensory inputs onto SC neurons.
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0.904 |
1988 — 1989 |
Rhoades, Robert 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. |
Damage Induced Trigeminal Organization @ University of Toledo Health Sci Campus
The research proposed will define the peripheral and central sequelae of trigeminal nerve damage and, in addition, determine whether these consequences can be altered by treatment with neuronal growth promoters such a bovine brain gangliosides. The application is composed of six projects, each of which will examine on aspect of the reorganization which follows transection of the infraorbital nerve in either adult or neonatal rats. PROJECT 1 will employ electron microscopic, multiple retrograde tracing and electrophysiological methods to address issues of ganglion cell survival and reorganization of peripheral connectivity. PROJECT 2 will use tranganglionic tracing and injection of individual, functionally characterized primary afferents with horseradish peroxidase (HRP) to determine the extent to which nerve damage or inactivation alters the primary afferent innervation of the trigeminal brainstem complex and whether changes in the central arbors of individual axons can be correlated with alterations in their peripheral connectivity. PROJECT 3 will concentrate upon potential changes in the brainstem organization. In these experiments, novel morphometric techniques will be employed to delineate the effects of both deafferentation and removal of targets upon the survival of trigeminal brainstem neurons. PROJECT 4 will employ retrograde tracing, electrophysiological and HRP injection techniques to delineate the effects of nerve damage or inactivation upon the morphology, response properties and projections of second order trigeminal neurons. PROJECT 5, like 4 and 3, will examine damage induced changes in the organization of the trigeminal brainstem complex. In these experiments, however, the emphasis will be upon monaminergic pathways which are well known to influence the responses of trigeminal neurons. PROJECT 6 will have as its focus studies concerned with the effects of treatment with bovine brain gangliosides upon neuronal survival and the events which surround and may influence axonal regeneration by surviving neurons. A parallel series of experiments will also examine the effects of gangliosides upon trigeminal ganglion cell survival and neuritogenesis in vitro.
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0.904 |
1990 — 1999 |
Rhoades, Robert 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. |
Trigeminal Primary Afferent Development @ University of Toledo Health Sci Campus
There is considerable evidence that competitive interactions play a major role in determining the both the morphological properties of, and distributions of functional synapses made by, afferents to a given central nervous system nucleus. However, it is not at all clear whether this is the case with respect to the trigeminal (V) primary innervation of the rat's brainstem. In fact, limited evidence (Belford and Killackey, '80; Durham and Woolsey, '84) has suggested that such interactions may play little or no role in the postnatal development of this pathway. We will determine whether competitive interactions influence either the pre- and/or postnatal development of V primary afferents by carrying out three experiments. First, we will use anterograde transport of Di-I and horseradish peroxidase (HRP) to label individual V primary afferents in both fetal and neonatal rats. These fibers will be reconstructed in the light microscope and distributions of synapses made by single axons will be determined by electron microscopy. Secondly, we will record from individual V primary afferents and neurons in V nucleus principalis (PrV) in fetal and newborn rats to determine whether the latter cells receive greater convergent input than is the case in adult animals. The results of these two studies will allow us to determine whether the substrate for competitive interactions among V primary afferents exists in fetal or early postnatal life. In a third and final experiment, we will use fetal surgical techniques to damage the peripheral axons of primary afferents that innervate selected vibrissae follicles. If competitive interactions shape the central arbors of vibrissa-related primary afferents, such lesions should put undamaged axons at a "competitive advantage" and increase the size of their central terminal arbors. We will use intra-axonal recording and HRP injection techniques to determine whether or not this occurs.
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0.904 |
1992 |
Rhoades, Robert W |
S10Activity Code Description: To make available to institutions with a high concentration of NIH extramural research awards, research instruments which will be used on a shared basis. |
Confocal Scanning Laser Microscope @ University of Toledo Health Sci Campus
This request is for a Bio-Rad Confocal Scanning Laser Microscope System. It will be used in conjunction with a Nikon Optiphot microscope equipped with episcopic fluorescence optics already in place in the Dept. of Anatomy at the Medical College of Ohio. The system will significantly enhance the research programs of ten major users, seven of whom are conducting N.I.H.-funded research projects. The microscope system will also be employed by four other users, three of whom will use it in N.I.H.-supported research. The microscope system will be employed in several distinctly different ways. Dr. Rhoades will use it primarily for the reconstruction of fluorescently-labelled primary afferent axons in fetal rats. Drs. Mooney, Chiaia, and Dun will employ it to assist in the reconstruction of neurons that are filled with Lucifer yellow in both in vitro and "dead-slice" preparations. Drs. Dun and Godfrey will employ the microscope system to reconstruct distributions of transmitters and transmitter-related enzymes in neural tissue. Drs. Lane, Mellgren, Morse, Budd, Pansky, Selman, and Chakraborty will employ the microscope to assist in defining the subcellular locations of antigens recognized by polyclonal and monoclonal antibodies and Dr. Wall will use it in the reflected light mode to assist in the reconstruction of the central terminations of horseradish peroxidase-labelled peripheral nerves in normal and nerve-damaged monkeys. Dr. Goldblatt will use the system for localization of new agents being developed for photodynamic tumor therapy and to assess the effects of such therapy upon the vascularization of tumors. The Bio-Rad system is-the best instrument available for the applications outlined in the preceding paragraph. The investigators whose projects comprise this application have evaluated the systems developed by Bio-Rad, Sarastro, and Zeiss and the performance of the Bio-Rad confocal microscope was superior to the other two systems. The preliminary data included in the application were obtained using the Bio-Rad microscope. The Medical College of Ohio has a strong institutional commitment to the acquisition and maintenance of this microscope system. A highly experienced and state-funded technician, Ms. Patricia McCann, will oversee the day-to-day operation of the microscope and a room in the Dept. of Anatomy will be renovated to house the system. The Medical College has also agreed to pay the service contract for the instrument if it is purchased.
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0.904 |
1996 — 1999 |
Rhoades, Robert 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. |
Serotonin and Retinotectal Development @ University of Toledo Health Sci Campus |
0.904 |