1985 — 1989 |
Karten, Harvey Jules |
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. |
Lamination of Ipl and Target Specific Ganglion Cells @ University of California San Diego
The laminar organization of ganglion cell dendrites within the inner plexiform layer (IPL) is a major determinant of their response properties. Distinct subsets of ganglion cells possess unique dendritic morphologies, receive defined afferent connections from amacrine and bipolar cells, and project upon specific central targets ("Target Specific Ganglion Cells"). Their action on the central target is modulated by their neurotransmitters/modulators. Using immunohistochemical methods, we have demonstrated the existence of diverse populations of chemically specific amacrine cells in all classes of vertebrates. Most recently we have discovered the presence of four major peptides in distinct subsets of frog retinal ganglion cells. Each ganglion cell subset terminates in separate central targets. This project will study the laminar organization and interaction of amacrine cells and ganglion cells within the IPL of mammals and birds. The project consists of three parts: I. Contributions of chemically defined populations of amacrine and ganglion cells to lamination in the IPL. II. Dendritic morphology and transmitters of retinal ganglion cells terminating in the optic tectum. III. Identification of transmitter specific subsets of amacrine cells in receipt of centrifugal projections from the brain. These studies will help identify ganglion cell transmitters, and contribute to our understanding of the basic microcircuitry of the retinal organization. Methods to be used include IHC, cDNA in situ hybridization, single cell filling, EM and pathway tracing methods.
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0.958 |
1985 — 1989 |
Karten, Harvey Jules |
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. |
Organotopic Specificity in Autonomic Pathways @ University of California San Diego
The mammalian neocortex is the product of a complex evolutionary history. Research on the organization of sensory projections to the telencephalon of nonmammalian vertebrates has demonstrated the presence of cortical equivalent "cluster" of neurons within the Dorsal Ventricular Ridge (DVR) of the telencephalon. These "clonal clusters" may correspond to individual laminae of the mammalian neocortex. The microcircuitry of connections between "clusters" within the tectofugal pathways appears to correspond to the interlaminar organization of extrastriate visual pathways of the neocortex. Further analysis of this pathway will help clarify the role of the extrastriate system in visual performance. Studies will concentrate on the organization of visual pathways within the DVR, the relationship of the DVR to the neocortex, and possible role of the subventricular zone of Stensaas in the ontogeny of neocortex in mammals. The DVR may correspond to the Subventricular Zone (SVZ) of Stensaas in the developing neocortex of mammals. Specific studies will include: A. Analysis of the organization, histochemistry and morphology of the neurons of the tectofugal pathway in the DVR of birds. B. Interrelationship of the thalamofugal and tectofugal pathways. C. Production of monoclonal antibodies to identify "clonal clusters" and their possible cross reactivity with single laminae of the neocortex of mammals. E. Investigate the role of the SVZ of mammals as a possible representative of the Dorsal Ventricular Ridge, and its participation in the development of neocortex. These studies will clarify our understanding of the role of tectofugal pathways in vision, the evolutionary origins of the mammalian neocortex, and both normal and abnormal developmental events in the ontogeny of the mammalian neocortex. Methods to be employed include pathway tracing methods, single cell filling, immunohistochemistry, monoclonal antibodies and in situ hybridization to identify the transmitters/peptides, receptors and related proteins mediating organization and communication in these two pathways.
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0.958 |
1990 — 1993 |
Karten, Harvey Jules |
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. |
Dvr: Visual Pathways and the Origins of Neocortex @ University of California San Diego
The mammalian neocortex is the product of a complex evolutionary history. Research on the organization of sensory projections to the telencephalon of nonmammalian vertebrates has demonstrated the presence of cortical equivalent "cluster" of neurons within the Dorsal Ventricular Ridge (DVR) of the telencephalon. These "clonal clusters" may correspond to individual laminae of the mammalian neocortex. The microcircuitry of connections between "clusters" within the tectofugal pathways appears to correspond to the interlaminar organization of extrastriate visual pathways of the neocortex. Further analysis of this pathway will help clarify the role of the extrastriate system in visual performance. Studies will concentrate on the organization of visual pathways within the DVR, the relationship of the DVR to the neocortex, and possible role of the subventricular zone of Stensaas in the ontogeny of neocortex in mammals. The DVR may correspond to the Subventricular Zone (SVZ) of Stensaas in the developing neocortex of mammals. Specific studies will include: A. Analysis of the organization, histochemistry and morphology of the neurons of the tectofugal pathway in the DVR of birds. B. Interrelationship of the thalamofugal and tectofugal pathways. C. Production of monoclonal antibodies to identify "clonal clusters" and their possible cross reactivity with single laminae of the neocortex of mammals. E. Investigate the role of the SVZ of mammals as a possible representative of the Dorsal Ventricular Ridge, and its participation in the development of neocortex. These studies will clarify our understanding of the role of tectofugal pathways in vision, the evolutionary origins of the mammalian neocortex, and both normal and abnormal developmental events in the ontogeny of the mammalian neocortex. Methods to be employed include pathway tracing methods, single cell filling, immunohistochemistry, monoclonal antibodies and in situ hybridization to identify the transmitters/peptides, receptors and related proteins mediating organization and communication in these two pathways.
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0.958 |
1990 — 1993 |
Karten, Harvey Jules |
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. |
Morphological &Chemical Specificity of Ganglion Cells @ University of California San Diego
Our long term objective is to characterize the morphological and biochemical diversity of retinal ganglion cells (RGCS), and to determine the central projections of individual types of ganglion cells. RGCs differ not only in morphology and central projections, but also in: a) the input they receive and hence the content of receptor molecules for various putative transmitters; b) second messengers; c) the nature and number of various putative transmitters and "neuromodulators" presumably released at their central targets; d) response to injury; and e) their selective ability to regenerate. Our immediate specific aims include: 1) Continue ongoing efforts to identify putative transmitters and neuropeptides in RGCS, and define their unique central projections. We presently are concentrating on the neuropeptides enkephalin and cholecystokinin. 2) Identify receptors for transmitters and trophic factors in different populations of ganglion cells, particularly nicotinic acetylcholine, GABA(A) and NGF receptors. 3) Attempt to clarify the role of transport of nAChR receptor molecules in ganglion cell axons to "nonsynaptic" sites in the optic tectum (so-called "spurious transport"). 4) Determine temporal patterns of expression of transmitters and receptors in retinal neurons during embryogenesis. These studies may help identify factors regulating ganglion cell transmitters, growth and response to injury, as in trauma and glaucoma. Methods: light and electron microscopic immunohistochemistry, in situ hybridization, anterograde and retrograde pathway tracing methods. Animals: Pigeons, chick embryos, frogs.
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0.958 |
1992 — 1999 |
Karten, Harvey Jules |
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. |
Dvr--Visual Pathways and the Origins of Neocortex @ University of California San Diego
The mammalian neocortex is the product of a complex evolutionary history. Research on the organization of sensory projections to the telencephalon of nonmammalian vertebrates has demonstrated the presence of cortical equivalent "cluster" of neurons within the Dorsal Ventricular Ridge (DVR) of the telencephalon. These "clonal clusters" may correspond to individual laminae of the mammalian neocortex. The microcircuitry of connections between "clusters" within the tectofugal pathways appears to correspond to the interlaminar organization of extrastriate visual pathways of the neocortex. Further analysis of this pathway will help clarify the role of the extrastriate system in visual performance. Studies will concentrate on the organization of visual pathways within the DVR, the relationship of the DVR to the neocortex, and possible role of the subventricular zone of Stensaas in the ontogeny of neocortex in mammals. The DVR may correspond to the Subventricular Zone (SVZ) of Stensaas in the developing neocortex of mammals. Specific studies will include: A. Analysis of the organization, histochemistry and morphology of the neurons of the tectofugal pathway in the DVR of birds. B. Interrelationship of the thalamofugal and tectofugal pathways. C. Production of monoclonal antibodies to identify "clonal clusters" and their possible cross reactivity with single laminae of the neocortex of mammals. E. Investigate the role of the SVZ of mammals as a possible representative of the Dorsal Ventricular Ridge, and its participation in the development of neocortex. These studies will clarify our understanding of the role of tectofugal pathways in vision, the evolutionary origins of the mammalian neocortex, and both normal and abnormal developmental events in the ontogeny of the mammalian neocortex. Methods to be employed include pathway tracing methods, single cell filling, immunohistochemistry, monoclonal antibodies and in situ hybridization to identify the transmitters/peptides, receptors and related proteins mediating organization and communication in these two pathways.
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0.958 |
1994 |
Karten, Harvey Jules |
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. |
Morphological and Chemical Specificity of Ganglion Cells @ University of California San Diego
Our long term objective is to characterize the morphological and biochemical diversity of retinal ganglion cells (RGCS), and to determine the central projections of individual types of ganglion cells. RGCs differ not only in morphology and central projections, but also in: a) the input they receive and hence the content of receptor molecules for various putative transmitters; b) second messengers; c) the nature and number of various putative transmitters and "neuromodulators" presumably released at their central targets; d) response to injury; and e) their selective ability to regenerate. Our immediate specific aims include: 1) Continue ongoing efforts to identify putative transmitters and neuropeptides in RGCS, and define their unique central projections. We presently are concentrating on the neuropeptides enkephalin and cholecystokinin. 2) Identify receptors for transmitters and trophic factors in different populations of ganglion cells, particularly nicotinic acetylcholine, GABA(A) and NGF receptors. 3) Attempt to clarify the role of transport of nAChR receptor molecules in ganglion cell axons to "nonsynaptic" sites in the optic tectum (so-called "spurious transport"). 4) Determine temporal patterns of expression of transmitters and receptors in retinal neurons during embryogenesis. These studies may help identify factors regulating ganglion cell transmitters, growth and response to injury, as in trauma and glaucoma. Methods: light and electron microscopic immunohistochemistry, in situ hybridization, anterograde and retrograde pathway tracing methods. Animals: Pigeons, chick embryos, frogs.
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0.958 |
1995 — 1998 |
Karten, Harvey Jules |
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. |
Cholinergic Modulation of Retinal Ganglion Cells @ University of California San Diego
DESCRIPTION (Adapted from investigator's abstract): The long term objective is to characterize the morphological and biochemical diversity of retinal ganglion cells (RGCs) and to determine the central projections of individual types of ganglion cells. About 20 percent of RGCs synthesize nicotinic acetylcholine receptors (nAChRs) and transport them to their axon terminals. It is proposed to study these RGC populations and examine the function of these transported receptors. The immediate specific aims include: (1) to characterize these RGCs containing nAChRs, including morphology, neurotransmitter receptor counts and their central projections; (2) to identify the source of cholinergic inputs that may act upon these RGC axonal terminals; (3) to determine if ACh-containing dendrites and/or axons form synapses upon retinal axons; (4) to determine if ganglion cell axonal nAChRs in tectum are functional and whether cholinergic agonists modify properties of retinal axonal terminals; (5) to determine the temporal pattern of innervation of axon-containing nAChRs into the tectum and ventral geniculate during development; and (6) to determine when during ontogeny nAChRs in RGCs become functional. These studies will help in determining the role of nicotine in visual function in the retina and the brain during embryogenesis and responses of RGCs to injury.
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0.958 |
1998 |
Karten, Harvey Jules |
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. |
Building a Neuron Oriented Database of the Retina @ University of California San Diego
DESCRIPTION (Adapted from applicant's abstract): We propose to continue our efforts towards the design and implementation of a database of the retina. To date, our work on database schema design and implementation has made us acutely aware of the considerable complexity and importance in the systematic classification and organization of cellular neuroscience data. Prior to developing a comprehensive neurosciences database a variety of issues in neuron classification using morphological and physiological properties must be addressed. This proposal considers these issues via the development of a suite of software tools to support improved data collection and visualization methodology, morphological and feature extraction from confocal images and the enumeration of a set of physiological features for inclusion in a database. Specifically, we propose a research effort that provides the following items: (1) Data Collection and Visualization - An improved method for collection of morphological and physiological data from intracellularly filled cells using the confocal microscope is proposed. We will also extend our MacVol volume visualization program to handle double and triple labeled datasets produced by the confocal microscope; (2)Classification (Morphology)- We will continue our efforts on the identification and extraction of morphological features from neuronal images. Empirical investigation of the use of these image features to support content-based retrieval operations in a database of such images will be conducted; (3) Classification (Physiology)-Our current database schema will be extended to more adequately handle the complexities of physiological data. Of specific interest are the kinds of data extracted using the methodology developed in the context of item (1) above; and (4) Data Comparison via a Neuron Browser-A library of neuronal images along with physiological descriptors will be developed. Software tools for querying and browsing images will also be implemented and made available.
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0.958 |
2001 — 2004 |
Karten, Harvey Jules |
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. |
Tectopulvinar System: Motion Detection and Evolution @ University of California San Diego
Comparative and evolutionary studies suggest that the tectopulvinar system is one of the most ancient components of the ascending pathways to the telencephalon and is vital to the process of motion detection. Improved understanding of this system may clarify the processing of visual information for detection of motion and direction in nonmammals and thus the evolution of such processing in mammals. The tectopulvinar system may be viewed as a series of visual information processing stages: Stage I processing-Retina: presumably simple On/Off cells with extremely small receptive fields; Stage II processing-Tectum: high speed motion detection by tectal neurons of the stratum griseum central (SGC) of birds and the lower stratum griseum superficiale (SGSL) of mammals in direct receipt of retinal inputs upon their unique "bottlebrush" dendritic endings; Stage III processing- Thalamus: global direction detection by specific thalamic neurons of the nucleus rotundus of birds and the nucleus inferior pulvinar in mammals; and Stage IV processing - Telencephalon: processing of directionality and possible restoration of retinotopy. This proposal is to study the substrate of motion detection and evolution of the tectopulvinar system in chicks, pigeons and squirrels, using immunohistochemistry, confocal microscopy, intracellular cell filling and physiological techniques to- answer the following questions: Studies of Stage II - Are motion detection cells of SGC/SGSL influenced by nonretinal inputs? We will examine the inputs from the nucleus isthmi and parabigemini, each the source of a major cholinergic projection upon the layer of bottlebrush dendritic endings in birds and mammals, respectively and of various telencephalic inputs. What is the topography of reciprocal connections of the tectum and the isthmi? Do cholinergic inputs influence the responses of bottlebrush dendritic endings to retinal stimulation? Studies of Stage III - How is directionality generated from motion by thalamic neurons? Specifically, how do SGC/SGSL neuronal axons terminate in the rotundus/inferior pulvinar? What is the three-dimensional morphology of rotundus/inferior pulvinar neurons in birds and mammals? Are there divisions in the inferior pulvinar of the squirrel that correspond to the divisions in the rotundus of birds? What are the physiological ro erties of the squirrel inferior pulvinar?
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0.958 |