GLYCINE EXERTS POTENT INHIBITORY ACTIONS ON MAMMALIAN OLFACTORY-BULB NEURONS

1. It is generally presumed that gamma-aminobutyric acid (GABA) mediates inhibition in the mammalian brain, whereas glycine is restricted to the brain stem and spinal cord. Recent immunocytochemical and molecular biological studies have demonstrated, however, a widespread distribution of glycine receptors throughout the CNS, including the olfactory bulb. To explore the functional significance of glycine receptors in olfactory bulb we have used primary culture and whole-cell voltage-clamp recording techniques to test the hypothesis that glycine, as well as GABA, exerts inhibitory actions on olfactory bulb neurons. 2. Cultures of olfactory bulb neurons contain two primary populations of morphologically distinct neurons, mitral/tufted cells and interneurons (granule and periglomerular cells). In all mitral/tufted cells and interneurons examined, both glycine and GABA evoked concentration-dependent desensitizing currents mediated by chloride, similar to those seen in mammalian neurons elsewhere in the brain and spinal cord. 3. The median effective concentration (EC(50)) for glycine was 125 mu M, with Hill coefficient of 1.7, whereas the EC(50) and Hill coefficient for GABA were 52 mu M and 1.8, respectively. These values are similar to values previously reported for other central neurons. 4. At moderate concentrations (> 1 mu M) strychnine nonselectively antagonised both glycine- and GABA-evoked currents. At low concentrations (less than or equal to 1 mu M) strychnine blocked glycine-mediated currents but had little effect on GABA-mediated currents. Similarly, picrotoxin was a nonselective antagonist for glycine- and GABA-mediated currents at high concentrations (100 mu M), but was selective for GABA at low concentrations (10 mu M). Bicuculline at moderate concentrations (3-10 mu M) had no effect on glycine-mediated currents but blocked GABA-evoked currents. 5. These results suggest that glycine and GABA activate different inhibitory amino acid receptors and that glycine as well as GABA may contribute to synaptic inhibition in the olfactory bulb.