INHIBITION IN THE SUPERIOR OLIVARY COMPLEX - PHARMACOLOGICAL EVIDENCEFROM MOUSE-BRAIN SLICE

1. The effects of gamma-aminobutyric acid (GABA) and glycine and their respective antagonists were determined for neurons in the mouse super ior olivary complex. Brain slices (400 mu m) were cut in the frontal p lane 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 con tralateral 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 intracell ular and extracellular recordings were studied before, during, and aft er 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. Simi lar effects were found in five cells tested with glycine (1-10 mM). Th ree neurons tested with both GABA and glycine were affected by both dr ugs. Extracellular spikes were blocked in 53 out of 67 LSO neurons tes ted 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 b oth. 4. GABA had a powerful blocking effect on extracellularly recorde d action potentials evoked by current-pulse stimulation of the trapezo id body in seven LSO neurons tested after adding the glycine receptor antagonist, strychnine (1 mu M), to the bath. GABA also lowered the me mbrane 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 neu rons and glycine produced a similar effect in 14 out of 26 neurons fro m which intracellular recordings were made. Six out of 14 neurons test ed with GABA and glycine responded to both. Extracellular spikes were eliminated or reduced in amplitude by GABA in 15 out of 44 cells and b y glycine in 40 out of 68 cells tested. Eleven out of 29 cells from wh ich extracellular recordings were made were affected by both. 6. The g lycine antagonist, strychnine (0.25-1.0 mu M), blocked both ipsilatera l and contralateral inhibitory postsynaptic potentials (IPSPs) in LSO. The GABA(A) antagonist, bicuculline (50-100 mu M), was much less effe ctive, but blocked or reduced the amplitude of IPSPs in some neurons. Picrotoxin also was relatively ineffective. The lack of evoked IPSPs i n 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 bac lofen (100 mu M), had no blocking effect on extracellularly recorded a ction potentials elicited by current pulse stimulation of the trapezoi d body in three LSO neurons.