NEUROPHYSIOLOGY AND ANATOMY OF MULTISENSORY PROCESSING
A Troy
Nathan S. Kline Institute For Psych Rescity: Orangeburg country: United States (us)
Grant 5R01DC011490-12 from National Institute On Deafness And Other Communication Disorders
Keywords: Action Potentials; Anatomy; Architecture; Area; Attention; Attention deficit hyperactivity disorder; Auditory; Auditory area; Auditory system; Autistic Disorder; Automobile Driving; Brain; cell type; Chemicals; Cognitive; Confocal Microscopy; Cues; Defect; Discrimination (Psychology); Disease; Electron Microscopy; Elements; Etiology; Evolution; Goals; Hearing; Hearing Impaired Persons; Hearing problem; Impaired cognition; Impairment; improved; indexing; Individual; instrument; Learning Disabilities; Location; Methods; Modeling; multisensory; neurochemistry; neuronal excitability; Neurons; neurophysiology; novel; operation; Pattern; Phase; Physiological; Physiology; Primates; Process; Property; public health relevance; receptor; Resolution; response; Role; Sampling; Schizophrenia; Sensory; Signal Transduction; somatosensory; sound; Source; Staging; Stimulus; Structure; Surface; Synapses; System; Testing; Time; Training; Visual
Relevance: Improved mechanistic understanding of the instrumental functions of neuronal oscillations in the processing of driving inputs, their manipulation by modulatory inputs, the underlying circuitry, and the way that attention orchestrates these elements, will enhance our mechanistic understanding of perceptual/cognitive impairment specific to hearing disorders, and in a spectrum of disorders including ADHD, autism and schizophrenia, where defects in normal connectivity, disruptions of neuronal synchrony and attentional impairments are prominent
Project start date: 2010-12-01
Project end date: 2015-11-30
Budget start date: 1-DEC-2011
Budget end date: 30-NOV-2012
5R01DC011490-12 (2012): $445119
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to A Troy
FUNCTIONAL ORGANIZATION OF AUDITORY CORTEX
A Troy
Vanderbilt Universitycity: Nashville country: United States (us)
Grant 5R01DC004318-10 from National Institute On Deafness And Other Communication Disorders
Abstract: The long-term goal of this research program is a comprehensive of human auditory cortex organization. What are its structural components and what are their functions? How do these elements work together to produce the perceptual experience of hearing? Underlying current conceptions is a regional (modular) system of organization formed by an interconnected group of cortical areas, but the number of areas involved and their connections are unknown for humans. A testable working model of human auditory cortex has not been developed, even though such models are fundamental to studies of auditory cortex in other species. To establish this model, detailed neuroanatomical analyses will be used to reveal the underlying structures that comprise this part of the brain. Efforts will focus on the planum temporale in the superior temporal lobe, which is thought to be an important region for integrating the neural codes required to perceive and interpret sound. Although often treated as a single area, the planum temporale appears to contain several areas that are anatomically and physiologically distinct. Temporal lobes will be obtained postmortem and processed for marker proteins of neurons, axons, neurofilaments, and key enzymes. Areas will be profiled and compared on the basis several measurements (surface area, cortical thickness, neuron density, optical density). The research will be guided and grounded by comparative studies of other primates, which continue to provide an invaluable foundation for studies of auditory cortex in humans. In addition, parallel studies in monkeys will focus on the connections and neuron response properties in the posterior temporal lobe that correspond to the human planum temporale. The relevance of this research applies broadly to patient populations in which the temporal lobe is involved, and directly supports related areas of research involving both normal and clinical populations. These include 1) Noninvasive methods to study auditory activity in the human brain (e.g., functional imaging); 2) Neurosurgical planning and assessment of function associated with surgery, injury, or related pathology (e.g., cerebrovascular accidents, tumors); 3) Evaluation of cortical function in clinical populations in which auditory processing or memory is affected (e.g., Alzheimer´s, schizophrenia, autism, dyslexia, epilepsy, language delay, hearing impairment, and aging); and 4) Maturational and genomic studies of auditory cortex in normal and clinical populations
Keywords: Accounting; Address; Affect; Aging; Alzheimer`s Disease; Animal Model; Area; Auditory; Auditory area; auditory stimulus; Autistic Disorder; Autopsy; Axon; base; Brain; Brain Part; Cells; Clinical; Code; comparative; Comparative Study; Conceptions; Data; density; design; Dimensions; Dyslexia; Elements; Enzymes; Epilepsy; Evaluation; experience; Foundations; Functional Imaging; Funding; Genomics; Goals; Grant; Hearing; hearing impairment; Human; Injury; insight; Knowledge; Language Delays; Lateral; Link; Macaca; Magnetic Resonance; Magnetic Resonance Imaging; Measurement; Medial; Memory; Methods; Modeling; Monkeys; neurofilament; Neurons; neurophysiology; nonhuman primate; Operative Surgical Procedures; Optics; Output; Pan Genus; Pathology; patient population; Phylogenetic Analysis; Physiological; Population; Primates; Process; programs; Property; Proteins; receptive field; relating to nervous system; Research; research study; response; Schizophrenia; Site; sound; Staging; stroke; Structure; Surface; System; Temporal Lobe; Thalamic Nuclei; Thick; Tissues; Tracer; tumor; Weight; Work
Project start date: 1999-12-01
Project end date: 2012-04-30
Budget start date: 1-MAY-2011
Budget end date: 30-APR-2012
5R01DC004318-10 (2011): $429077
MECHANOTRANSDUCTION AND THE REGULATION OF SKELETAL MUSCLE MASS
A Troy, Assistant Professor
University Of Wisconsin Madisoncity: Madison country: United States (us)
Grant 5R01AR057347-02 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases
Abstract: Mechanical stimuli play a major role in the regulation of skeletal muscle mass, and the maintenance of muscle mass contributes significantly to disease prevention and the quality of life. Although the link between mechanical stimulation and the regulation of muscle mass has been recognized for decades, the molecular mechanisms underlying this process are not known. Hence, the long-term goal of our research is to define the molecular events through which mechanical stimuli regulate skeletal muscle mass. The primary objective of this project is to define the role of the mammalian target of rapamycin (mTOR) in regulating skeletal muscle mass, and determine how mechanical stimuli activate mTOR signaling. Our rationale for focusing on mTOR comes from our preliminary studies which suggest that i) the activation of mTOR plays a critical role in mechanically-induced growth, and ii) mechanical stimuli activate mTOR signaling through a unique PI3K/PKB- independent mechanism involving phosphatidic acid (PA). Given that mechanical stimuli activate mTOR, it follows that a molecular mechanism (i.e. mechanotransduction pathway) exists for converting mechanical signals into mTOR activation. Thus, our plan is to identify the critical events in this pathway and determine if mimicking these events can induce muscle growth and attenuate disuse atrophy. Our current hypothesis is that mechanical stimuli promote an increase in phosphatidic acid (PA) which subsequently activates mTOR signaling and ultimately growth. To test this hypothesis we will pursue the following four specific aims 1) Determine if the activation of mTOR is sufficient to induce growth and attenuate disuse atrophy; 2) Define the role of mTOR in mechanically-induced growth; 3) Determine if an increase in [PA] is sufficient to induce growth and attenuate disuse atrophy and 4) Identify the upstream molecules that regulate the mechanical activation of mTOR. In the first aim, over-expression of Rheb will be used to induce a PI3K/PKB-independent activation of mTOR in mouse skeletal muscles, and the resulting effect on muscle mass during normal use and disuse will be determined. In the second aim, transgenic mice expressing various mutants of mTOR will be used to define the muscle specific role of mTOR, and mTOR kinase activity, in mechanically-induced growth. In the third aim, over-expression of PA synthesizing enzymes will be used to determine if an increase in [PA] is sufficient to induce growth and attenuate disuse atrophy. In the fourth aim, activity assays will be used to identify the enzymes that regulate mechanically-induced changes in PA, and then pharmacological and molecular interventions will be used to further define the role that these enzymes play in the mechanical activation of mTOR. The proposed studies are significant because the outcomes will fill major gaps in our current knowledge of how mechanical stimuli regulate mTOR signaling and skeletal muscle mass. Furthermore, the outcomes could lead to the identification of targets for therapies that mimic the effects of mechanical stimuli and, in-turn, prevent atrophy during periods of disuse such as bedrest, immobilization and aging
Keywords: Aging; Assay; Atrophic; Atrophy; Atrophy, Muscle; Attenuated; base; Bed rest; Bedrest; Bioassay; Biologic Assays; Biological Assay; biological signal transduction; Cachexia; Cell Communication and Signaling; Cell Signaling; disease prevention; disorder prevention; Disuse Atrophy; Dose; EC 2.7; Elements; enzyme activity; Enzymes; Event; Foundations; Future; Generalized Growth; Genetic; Goals; Growth; Health; heavy metal lead; heavy metal Pb; Immobilization; immobilization of body part; inhibitor; inhibitor/antagonist; innovate; innovation; innovative; Intermediary Metabolism; Intervention; intervention development; Intervention Strategies; interventional strategy; Intracellular Communication and Signaling; Kinases; Knowledge; Lead; Link; Maintenance; Maintenances; mammalian target of rapamycin (mTOR); Mammals, Mice; Mechanical Stimulation; Mechanics; member; Metabolic Processes; Metabolism; METBL; Mice; Molecular; mTOR gene product; mTOR protein; Murine; Mus; Muscle; muscle form; Muscle Tissue; Muscle, Skeletal; Muscle, Voluntary; Muscular Atrophy; mutant; novel; ontogeny; orthopedic freezing; Outcome; Outcome Study; pathway; Pathway interactions; Pb element; Peptide Biosynthesis, Ribosomal; Phosphatidic Acid; Phosphotransferases; Play; prevent; preventing; Process; Protein Biosynthesis; Protein Biosynthesis, Ribosomal; protein synthesis; Protein Synthesis, Ribosomal; QOL; Quality of life; RAFT-1 gene product; Rapamune; Rapamycin; Regulation; Research; Resistance; resistant; Role; Senescence; senescent; Signal Transduction; Signal Transduction Systems; Signaling; Sirolimus; Skeletal muscle structure; Skeletal Muscle Tissue; social role; Space Flight; Spaceflight; Stimulus; Technology; Testing; therapy development; Tissue Growth; Transgenic Mice; Transphosphorylases; treatment development; Work
Relevance: The proposed studies have broad application to health-related research and could lead to the development of therapies aimed at preventing skeletal muscle atrophy during conditions such as bedrest, immobilization, spaceflight, aging, cachexia and dystrophy
Project start date: 2010-04-01
Project end date: 2015-02-28
Budget start date: 1-MAR-2011
Budget end date: 29-FEB-2012
PFA/PA: PA-07-070
5R01AR057347-02 (2011): $270641