SYNAPTIC PHARMACOLOGY OF THE SUPERIOR OLIVARY COMPLEX STUDIED IN MOUSE-BRAIN SLICE

The synaptic pharmacology of the lateral superior olive (LSO) and medial nucleus of the trapezoid body (MNTB) was examined in a brain slice preparation of the mouse superior olivary complex (SOC). Physiological responses in SOC were elicited by electrical stimulation of the trapezoid body ipsilateral or contralateral to the recording site, and bilateral interactions were investigated by combined ipsilateral and contralateral stimulation. Pharmacological effects were tested by bath application of amino acid agonists and antagonists. Neurons in MNTB were excited by contralateral stimulation and unaffected by ipsilateral stimulation. Excitatory amino acid (EAA) agonists-kainic acid (KA), quisqualic acid (QA), or L-glutamate-caused spontaneous firing at low concentrations and eliminated responses at higher concentrations in MNTB. The EAA agonist NMDA had relatively little effect at comparable concentrations. Stimulus-elicited responses were blocked by non-NMDA antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX) and by the nonspecific EAA antagonist kynurenic acid, but were unaffected by the NMDA antagonist D,L-2-amino-5-phosphonovaleric acid (APV). LSO neurons were typically excited by ipsilateral stimulation and inhibited by contralateral stimulation. In LSO, KA, QA, and L-glutamate caused spontaneous firing at low concentrations and eliminated responses at higher concentrations, and NMDA had relatively little effect. Excitatory responses in the vast majority of LSO neurons were blocked by CNQX, DNQX, or kynurenic acid. Some responses were also blocked by APV. LSO neurons were affected by glycine, and contralateral inhibition in LSO was completely blocked by strychnine. NMDA also blocked inhibition in LSO. These results indicate that excitation of both MNTB and LSO neurons is mediated primarily by an EAA neurotransmitter through non-NMDA receptors and that contralateral inhibition of LSO cells is mediated through strychnine-dependent glycine receptors. NMDA receptors may play a role in binaural processing by modulating contralateral inhibitory input to LSO.