NMDA and AMPA Receptors in the Dorsal Nucleus of the Lateral Lemniscus Shape Binaural Responses in Rat Inferior Colliculus

Abstract

Binaural responses of single neurons in the rat's central nucleus of the inferior colliculus (ICC) were recorded before and after local injection of excitatory amino acid receptor antagonists (either 1,2, 3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium [NBQX], (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid [CPP], 6-cyano-7-nitroquinoxaline-2,3-dione [CNQX], or (+/-)-2amino-5-phosphonovaleric acid [APV]) into the dorsal nucleus of the lateral lemniscus (DNLL). Responses were evoked by clicks delivered separately to the two ears at interaural time delays between -1.0 and +30 ms (positive values referring to ipsilateral leading contralateral click pairs). The neurons in our sample were excited by contralateral stimulation and inhibited by ipsilateral stimulation, and the probability of action potentials was reduced as the ipsilateral stimulus was advanced. Binaural inhibition resulted in response suppression that lasted up to 30 ms. Injection of excitatory amino acid antagonists into the DNLL contralateral to the recording site reduced the strength of binaural inhibition in the ICC. The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist NBQX preferentially affected responses at small interaural time intervals (0-1.0 ms), whereas the N-methyl-D-aspartate (NMDA) antagonist CPP preferentially affected responses at longer intervals (1-30 ms). Both CNQX and APV produced a release from binaural inhibition, but neither drug was selective for specific intervals. The data support the idea that binaural inhibition in the rat ICC is influenced by both AMPA and NMDA receptor-mediated excitatory events in the contralateral DNLL. The results suggest that the AMPA receptors contribute selectively to the initial component of binaural inhibition and the NMDA receptors to a longer lasting component.