INHIBITION IN THE SUPERIOR OLIVARY COMPLEX - PHARMACOLOGICAL EVIDENCE FROM MOUSE-BRAIN SLICE

1. The effects of gamma-aminobutyric acid (GABA) and glycine and their respective antagonists were determined for neurons in the mouse superior olivary complex. Brain slices (400 mu m) were cut in the frontal plane and maintained in an oxygenated saline solution for physiological recording. Recordings were made from neurons in the lateral superior olive (LSO) or medial nucleus of the trapezoid body (MNTB) with glass micropipettes filled with 4 M potassium acetate. 2. Ipsilateral and contralateral synaptic responses were elicited by applying current pulses to the trapezoid body through bipolar stimulating electrodes located at positions lateral and medial to the olivary complex. Both intracellular and extracellular recordings were studied before, during, and after application of drugs to the saline bath containing the tissue slice. 3. Intracellular recordings from 10 neurons in LSO showed that GABA (1-10 mM) caused a concentration-dependent drop in membrane resistance and either reduced or blocked postsynaptic excitatory responses. Similar effects were found in five cells tested with glycine (1-10 mM). Three neurons tested with both GABA and glycine were affected by both drugs. Extracellular spikes were blocked in 53 out of 67 LSO neurons tested with GABA and 29 out of 35 neurons tested with glycine. Seventeen out of 23 neurons tested with both GABA and glycine were affected by both. 4. GABA had a powerful blocking effect on extracellularly recorded action potentials evoked by current-pulse stimulation of the trapezoid body in seven LSO neurons tested after adding the glycine receptor antagonist, strychnine (1 mu M), to the bath. GABA also lowered the membrane resistance of one LSO neuron in which intracellular recordings were made in the presence of strychnine. 5. Neurons in MNTB also were affected by GABA and glycine but the proportion of sensitive cells was less than in LSO. GABA reduced membrane resistance in 6 out of 16 neurons and glycine produced a similar effect in 14 out of 26 neurons from which intracellular recordings were made. Six out of 14 neurons tested with GABA and glycine responded to both. Extracellular spikes were eliminated or reduced in amplitude by GABA in 15 out of 44 cells and by glycine in 40 out of 68 cells tested. Eleven out of 29 cells from which extracellular recordings were made were affected by both. 6. The glycine antagonist, strychnine (0.25-1.0 mu M), blocked both ipsilateral and contralateral inhibitory postsynaptic potentials (IPSPs) in LSO. The GABA(A) antagonist, bicuculline (50-100 mu M), was much less effective, but blocked or reduced the amplitude of IPSPs in some neurons. Picrotoxin also was relatively ineffective. The lack of evoked IPSPs in MNTB precluded any testing with glycine or GABA antagonists in that structure. 7. The GABA(B) receptor antagonist, phaclofen (0.5 mM), had no effect on IPSPs in four LSO neurons. Also, the GABA(B) agonist baclofen (100 mu M), had no blocking effect on extracellularly recorded action potentials elicited by current pulse stimulation of the trapezoid body in three LSO neurons.