• Walsh, Edward J (PI)

    Project: Research project

    Project Details


    The broad, long-term objective of the proposed research is to characterize
    the neurophysiological and neuropharmacological aspects of neuronal
    development in the cochlear nuclear (CN) complex. This research is part of
    an even broader objective, which is to develop a comprehensive model of
    mammalian auditory development that will support biomedical research
    designed to determine the influence of environmental hazards on the
    development of auditory function in humans, as well as the development of
    pharmaceuticals engineered to ameliorate congenital and environmentally
    induced auditory pathology. Based upon results from previous research,
    several hypotheses are to be tested in proposed experiments: (1) on the
    basis of known innervation time courses, that the development of excitatory
    function subserved via glutamatergic membrane receptors precedes the
    development of functional GABA and glycine mediated inhibition, (2) that
    extrinsic influences (cochlear, other neural networks, etc.),, rather than
    intrinsic properties of CN neurons, underlie observed response immaturities
    and (3) that the development of presynaptic elements rate limits
    'functional synaptogenesis' in CN. The frequency-dependent aspects of the
    development of GABA and glycine mediated inhibition among CN neurons will
    be studied directly for the first time in an auditory structure, among a
    population of neurons never before studied. Also, changes associated with
    concentrations and function of endogenous amino acids will be studied
    during developmental periods exhibiting extensive synaptogenic and
    neurotrophic activity. To achieve the stated objectives, experiments
    involving standard single neuron electrophysiology in combination with
    microionophoresis procedures will be performed and standard physiological
    and pharmacological procedures will be utilized (i.e., current/or
    dose/response curve analyses, amino acid modulation of discharge rate vs.
    sound level functions, acoustically-evoked temporal discharge patterns,
    etc.) to characterize neurons in this brainstem nucleus. In addition, high
    performance liquid chromatography (HPLC) and combined electrochemical
    detection methods will be used to determine the concentrations of GABA and
    glycine available in specific CN regions throughout postnatal development.
    Their concentrations will be analyzed in relation to electrophysiology and
    pharmacology results, particularly with regard to experimental paradigms
    designed to illuminate our understanding of the relevance of developmental
    changes associated with endogenous ligand actions. Results of proposed
    research will provide a firm understanding of certain key molecular events
    underlying central auditory system development.
    Effective start/end date6/1/905/31/96


    • National Institutes of Health: $120,079.00
    • National Institutes of Health: $112,921.00


    • Medicine(all)
    • Neuroscience(all)


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