• Walsh, Edward J (PI)

    Project: Research project

    Project Details


    Response properties of developing auditory neurons suggest that synaptic
    function may be immature during early postnatal development. Response
    latencies are prolonged, temporal discharge patterns do not display the
    characteristic adult-like patterns, dynamic ranges of input/output
    functions are greatly reduced, and discharge synchronization (i.e.,
    phase-locking) is diminished. To determine the contribution that immature
    synapses make to these developing response patterns, we propose to study
    the electrophysiological and pharmacological development of neurons within
    the dorsal (DCN) and posteroventral (PVCN) cochlear nuclei (CN) of
    kittens. The overall hypothesis to be tested is that immature response
    properties of DCN and PVCN neurons recorded from young animals are the
    result of immature synaptic mechanisms. Synaptic transmission will be
    assessed electrophysiologically by examining neuronal responses to acoustic
    stimulation throughout postnatal development. We will evaluate
    postsynaptic receptor function prior to the age at which
    acoustically-evoked responses are elicited (e.g., between birth and 5-7
    postnatal days), by examining the effects of excitatory (glutamate and
    aspartate) and inhibitory (gamma-aminobutyric acid (GABA) and glycine)
    amino acids microiontophoretically applied onto DCN and PVCN neurons.
    Receptor specificity of amino acid-mediated excitation or inhibition will
    be evaluated by the simultaneous administration of specific receptor
    antagonists during amino acid application and during acoustic stimulation.
    Throughout development, we will determine the effects of the putative amino
    acid neurotransmitters and their antagonists on discharge rate, discharge
    synchronization, response thresholds, the frequency limits of
    responsiveness, and on temporal discharge patterns throughout the response
    area of CN neurons. Finally, we hypothesize that the time course of
    receptor activation (i.e., time to maximum effect) following amino acid
    administration, and the time course over which discharge activity is
    terminated after cessation of microiontophoresis, varies during postnatal
    development, and that the characterization of that process can be used to
    map the maturation of synaptic transmission within the CN. These studies
    represent an initial investigation of developmental aspects of chemical
    neurotransmission in the auditory system, which is an important first step
    in the development of therapeutic, pharmacologic strategies aimed at the
    treatment of hearing anomalies that may be characterized by neurochemical
    Effective start/end date9/1/868/31/89


    • National Institutes of Health


    • Medicine(all)
    • Neuroscience(all)


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