Contribution of AMPA and NMDA receptors to excitatory responses in the inferior colliculus

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Hearing Research





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Brain slice studies of neurons in the central nucleus of the inferior colliculus (ICC) indicate that excitatory responses evoked by electrical stimulation of the lateral lemniscus consist of two components, an early, rapid response mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and a later, a slower one mediated by N-methyl-D-aspartate (NMDA) receptors. The early response can be selectively blocked by AMPA receptor antagonists (1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium [NBQX]; or 6-cyano-7-nitroquinoxaline-2,3-dione) [CNQX], and the later one by NMDA receptor antagonists ((±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid [CPP]; or (±)-2-amino-5-phosphonovaleric acid) [APV]. Both AMPA and NMDA receptor-mediated responses can be elicited at resting potential, although the NMDA response is voltage dependent and makes a greater contribution when the cell membrane is depolarized. In vivo studies indicate that both AMPA and NMDA receptors contribute to sound-evoked responses. Both AMPA and NMDA receptor antagonists reduce the firing rate of single neurons in the ICC to contralaterally presented tones. Both classes of antagonist lower evoked activity over a wide range of sound intensities from threshold to maximum sound pressure levels. Thus, both NMDA and AMPA receptors contribute to responses over the full dynamic range of auditory sensitivity. The AMPA receptor antagonist, NBQX, is more effective than the NMDA receptor antagonist, CPP, in blocking responses of onset cells. Furthermore, NBQX and CPP have preferential effects in blocking the early or late responses of neurons that exhibited sustain activity to a 100 ms tone. Excitatory responses to sinusoidally amplitude-modulated stimuli are also reduced by application of either AMPA or NMDA antagonists. However, the synchrony of firing of action potentials to the modulation period (vector strength) is largely unaffected. The data suggest that the synchrony of firing of neurons in the inferior colliculus is determined primarily by the pattern of activity at lower levels of the auditory pathway and/or the local intrinsic properties of the cells. © 2002 Elsevier Science B.V. All rights reserved.