CODING IN AUDITORY NEURONS--EFFECTS OF AMINO ACIDS

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Neurological abnormalities including receptive aphasia, neural presbycusis and auditory perceptual dysfunction may involve neurochemical faults. This proposal examines the role neurotransmitters have in coding acoustic information with the goal of identifying and characterizing possible consequences neurotransmitter loss has on normal aging and pathologic communicative disorders. Proposed studies will evaluate neurotransmitter functions in mediating synaptic transmission in the cochlear nucleus (CN) and inferior colliculus (IC). Pharmacological effects of iontophoretically applied drugs will be examined using several different acoustic paradigms. This laboratory has successfully identified neurotransmitters and their functions at several key brainstem auditory circuits using similar neurophysiological and neuropharmacological techniques proposed in the present study. In anterior ventral cochlear nucleus (AVCN) several studies support roles for amino acids gamma-amino-n-butyric acid (GABA) and glycine as inhibitory neurotransmitters. Tests of mimicry (identity of action) and antagonism (pharmacologic identity) using selective receptor agonist and antagonists of synaptically released compounds will: 1) examine differential effects of GABAA, GABAB and glycine I related compounds iontophoretically applied onto three AVCN response types. Exciting preliminary results indicate that for certain response types, near-CF and rate dependent saturation responses but not lateral inhibition may be partially controlled by these neurotransmitters. Considerable evidence supports a role for excitant amino acid (EAA) neurotransmitters acting at acoustic nerve synapses in CN. Improved examination of receptors mediating sound-evoked excitation in CN is now possible with new, more selective, EAA receptor antagonists. DL-2-amino-5-phosphonovaleric acid (AP5), a selective N-methyl-D-aspartate (NMDA) receptor antagonist, will be compared to the new, selective, non-NMDA receptor antagonist 6,7-dinitroquinoxaline- evoked responses in CN. The rat IC undergoes a significant age-related loss of GABA (11,12,43). Iontophoretic studies in young adult Fischer-344 (F-344) rat will extend previous findings as to the role GABA plays in processing binaural and intensity information in IC. After confirmation of GABA's role in specific acoustic paradigms in CIC, physiological studies in aged F-344 rats will be used to assess age-related changes in GABA function. Data obtained from young adult F-344 rat IC will be compared to a similar iontophoretic study in adult chinchilla IC which will focus on phase sensitivity in on-low CF neurons. Age-related loss of inhibitory function in rat IC may have implications for understanding neural presbycusis in man which is characterized by a loss of speech intelligibility and inability to detect signal in noise.