ONTOGENY OF COCHLEAR NUCLEUS RESPONSES TO AMINO ACIDS

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
imbalance.