The specific aim in the proposed work is to identify post-synaptic receptors mediating the primary afferent response to vestibular and auditory stimulation in the chicken (Gallus domesticus, ages 11 to 14 days old). To do this we have developed a perilymphatic perfusion system for the avian auditory and vestibular end organs. Using vestibular and auditory compound action potentials (VCAP and ACAP respectively), we will test the effects of specific receptor blockers on the activation of vestibular and auditory neurons. The VCAP and ACAP tests will enable the measurement of dose response curves for auditory and vestibular neurons at each drug concentration chosen under otherwise identical physiological conditions. These techniques will be employed to critically test the following hypotheses in the chicken. Hypothesis 1: The primary afferent receptors mediating auditory compound action potentials are glutamate non-NMDA receptors. Hypothesis 2: The primary afferent receptors mediating vestibular compound action potentials are NMDA glutamate and/or GABA receptors. Using perilymphatic perfusion in a well-controlled physiological preparation, the effects of appropriate micromolar (mM) concentrations of drugs will be studied in situ. The effects of six chemical agents on evoked auditory and vestibular activity will be evaluated. To test hypothesis 1, non-NMDA receptor antagonists (6-cyano-7-nitroquinoxaline-2,3- dione [CNQX] and 6,7-dinitroquinoxaline-2,3-dione [DNQX]) will be used. Hypothesis 2 will be tested in two parts: 1) the role of NMDA receptors will be assessed using glutamate NMDA antagonists (D-a-aminoadipic acid [DAA] and D-L-2- amino-5-phosphonovaleric acid [APV]); and 2) response mediation by GABA receptors will be tested using GABA-A receptor antagonists bicuculline and picrotoxin. Significant reduction or blockade of responses in micromolar dose ranges will support the respective hypotheses. The absence of effects at all doses will rule out a critical role for the respective receptor types in the generation of the ACAP and VCAP.
|Irons-Brown, Shunda R; Jones, Timothy A (2004) Effects of selected pharmacological agents on avian auditory and vestibular compound action potentials. Hear Res 195:54-66|
|Irons-Brown, Shunda R; Jones, Sherri M; Jones, Timothy A (2003) The simultaneous in vivo perilymphatic perfusion of avian auditory and vestibular end organs. J Neurosci Methods 131:57-64|