1985 — 1993 |
Baker, Robert G |
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. |
Eye Movement: Physiological Organization
The specific aim of this research is to study in the cat certain brain stem nuclei and pathways essential for the control of eye movement. The long term goal of these experiments is to establish the neuronal operations of the vertebrate oculomotor system, especially that of its prenuclear elements during eye movement. Toward that end the specific goals of the present project period are related to ascertaining the origin and function of those brain stem nuclei utilizing principally the medial longitudinal fasciculus to regulate eye movements by either directly terminating on ocular motoneurons or indirectly by supranuclear connections through the latter areas. Morphological and physiological studies are planned to deal with major areas of uncertainty concerning vestibular, peri-hypoglossal, reticular and accessory ocular nuclei connections. The techniques to be utilized will be the standard electrophysiological ones comprising intra- and extracellular recordings from neurons and axons in anesthetized and alert cat preparations. Particular emphasis will be placed upon obtaining both anti- and orthodromic identification of central neuronal elements in the alert cat paradigm as identifcation criteria are developed from the anesthetized preparation. Morphological studies including lesion, degeneration and retrograde horseradish peroxidase will be designed to afford, via light and electron microscopy, a general picture of ocular sensorimotor organization. The studies outlined in this proposal should provide fundamental information concerning intrinsic organization of the ocular nuclei and the immediate premotoneuronal nuclei which are involved in the control of vertical and horizontal eye movement.
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0.958 |
1986 — 1990 |
Baker, Robert G |
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. |
Eye Movement Physiological Organization
Our present understanding of the neuronal and synaptic organizataion of the vertebrate oculomotor system has derived largely from the study of mammalian eye movements. Past efforts have centered around a detailed morphological and physiological analysis of the individual neuronal elements within the oculomotor system in order to better interpret neuronal form in view of cellular function. This overall goal will be continued with major reliance on the use of intracellular recording and HRP staining of identified neurons in the alert animal paradigm. This approach is to be substantially strengthened by including a carefully planned phylogenetic analysis of particular neurons and circuits in the coulomotor system. Assuming that a conservative neuronal plan extends throughout vertebrate oculomotor phylogeny, it is argued that knowledge of vertical and horizontal eye movement in antecedent vertebrates can contribute to a better understanding of basic principles and concepts underlying descendent CNS organization. The research plan encompasses 5 specific areas each of which employ similar experimental approaches, but utilize quite different species. (1) Phylogeny of the abducens nucleus with specific emphasis on internuclear neuron organization will be studied extensively from its first appearance in vertebrates up to, and including, mammals. (2) Synaptic and ionic mechanisms underlying horizontal and vertical saccadic organization will be examined largely in fish. (3) Inhibitory and excitatory second-order vestibulo-ocular neurons will be explored initially in fish, but also in descendent species with focus on their relationship to the phylogenetic origin, history and role of the trochlear motor nucleus in eye movement. (4) Mammalian oculomotor internuclear neurons will be studied and their origin will be sought in antecedent species. (5) Neuronal and synaptic effects of axotomy and regeneration will be evaluated centrally and in respect to neurogenic and myogenic influences on extraocular muscle fiber differentiation. Overall, the plan is to study homologous neurons and circuitry throughout the evolutionary scale in order to provide a solid basis for clarifying their role in mammals. All work envisioned is consistent with the goal of elucidating important relationships in the oculomotor system underlying gaze control and, concommmitantly, a better understanding of oculomotility disorders.
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0.958 |
1994 — 2005 |
Baker, Robert G |
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. |
Eye Movement--Physiological Organization |
0.958 |
1996 — 2000 |
Baker, Robert |
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. |
Neuronal Basis of Motor Learning and Memory in Brainstem and Cerebellar Circuits @ New York University School of Medicine
The goal of this proposal is to delineate the brain stem and cerebellar circuits that produce horizontal eye movement and to determine the synaptic sites and mechanisms responsible for motor adaptation. Intra- and extracellular single cell recording combined with neuronal marking techniques have characterized most of the circuits responsible for producing vestibulo- and visuo-ocular reflexes. The actual elements of the neuronal circuits involved and the pharmacological properties of the various synaptic links are now well enough understood to propose models that specify the brain stem sites for adaptive plasticity and the roles of vestibulo-cerebellar Purkinje cells. These models provide the basis for four experimental aims. First, the afferent and efferent organization of eye movement related vestibular and prepositus neurons will be studied with the intra- and extracellular application of biocytin and fluorescent probes. The goal is to specify the morphological architecture necessary for all signal transformations. Second, vestibular and prepositus neuronal activity will be recorded during visuo-/vestibulo-motor adaptation to directly assess the causality of signal processing and specify cellular sites of plasticity. Third, the membrane properties and conductances of vestibular and prepositus neurons will be characterized to determine their roles in integration and motor adaptation. An in vivo pharmacological model will be implemented to examine motor plasticity. Fourth, the role of, and interaction between, the prepositus and inferior olivary mossy/climbing fiber cerebellar circuits will be studied by using electrical, chemical and surgical techniques. The overall objective of this project is to specify the neuronal circuitry both necessary and sufficient for visual and vestibular oculomotor performance, learning and memory. These studies address in cellular and pharmacological terms the inductive mechanisms employed in the acquisition and translation of sensory signals into adaptive motor behavior. The neurophysiological findings should be of significance for achieving a theoretical framework of motor co-ordination in other vertebrates while providing an accessible detailed neuronal organization in teleosts for future genetic and molecular studies of movement control.
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1 |
2007 — 2014 |
Baker, Robert G |
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. |
Eye Movement: Physiological Organization @ New York University School of Medicine
DESCRIPTION (provided by applicant): The purpose of this research is to study the ontogeny of oculomotor neuron physiology and behavior by exploiting the developmental genetics of zebrafish. To achieve this objective, we will investigate the physiology and genetic specification of four neuronal subtypes that contribute to the production of horizontal and torsional eye movement. The proposed research will focus on quantifiable behaviors and physiological properties of oculomotor neurons and circuits to explore the role of Hox paralog group 4 genes (hoxa4a, Hoxb4a, hoxc4a, hoxd4a) in the patterning and differentiation of three nuclei specific for horizontal eye motion that originate from hindbrain rhombomeres 7 and 8. The first nucleus, PNI, performs a neural integration to provide an eye position signal essential for horizontal fixation and vestibuloocular reflex performance. The second, VNI, encodes eye velocity and provides the major input signal to the vestibulocerebellum, and thus is instrumental in all oculomotor plasticity paradigms. A third nucleus, the inferior olive (IO), provides climbing fiber input to the cerebellum necessary for eye movement stability. In addition, the physiology and development of the tangential nucleus (TAN) will be studied. TAN is responsible for gravitoinertial compensatory eye reflexes and develops in rhombomere 5 under control of Hox paralog group 3 genes. Otolith-induced torsional eye motion will provide an assay for cross-regulatory effects between Hox4 and Hox3 genes. The first aim of the project will characterize the electrophysiology, morphology, and behavior of identified hindbrain oculomotor neurons endogenously labeled with reporter proteins driven by specific Hox gene regulatory sequences. The second aim will use targeted misexpression of each Hox4 paralog to produce changes in neuronal structure / function and eye movements (as documented in Aim 1) to test the contributions of Hox4 genes to specification of PNI, VNI, IO and TAN neurons. The third aim will use perturbation of retinoic acid-sensitive regulatory pathways to manipulate hindbrain segmentation and neuronal specification to identify additional genes required for origin, migration and function of the four oculomotor nuclei. Disruptions in the genetic regulatory cascades specifying these oculomotor subgroups will be directly linked to morphological and electrophysiological alterations in their task specific neural networks as reflected in behavioral sequelae. The overall objective of the proposed work is to analyze oculomotor neurons and behaviors that have been functionally conserved throughout vertebrate evolution to establish a basis for understanding the developmental genetic underpinnings of human oculomotor behavior and eye movement disorders.
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0.958 |
2007 — 2011 |
Baker, Robert G |
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. |
Brainstem and Cerebellar Control of Horizontal Eye Movement @ New York University School of Medicine |
0.958 |