GLYCINE EXERTS POTENT INHIBITORY ACTIONS ON MAMMALIAN OLFACTORY-BULB NEURONS

1. It is generally presumed that gamma-aminobutyric acid (GABA) mediat es inhibition in the mammalian brain, whereas glycine is restricted to the brain stem and spinal cord. Recent immunocytochemical and molecul ar biological studies have demonstrated, however, a widespread distrib ution 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-cla mp recording techniques to test the hypothesis that glycine, as well a s GABA, exerts inhibitory actions on olfactory bulb neurons. 2. Cultur es of olfactory bulb neurons contain two primary populations of morpho logically distinct neurons, mitral/tufted cells and interneurons (gran ule and periglomerular cells). In all mitral/tufted cells and interneu rons examined, both glycine and GABA evoked concentration-dependent de sensitizing currents mediated by chloride, similar to those seen in ma mmalian neurons elsewhere in the brain and spinal cord. 3. The median effective concentration (EC(50)) for glycine was 125 mu M, with Hill c oefficient of 1.7, whereas the EC(50) and Hill coefficient for GABA we re 52 mu M and 1.8, respectively. These values are similar to values p reviously reported for other central neurons. 4. At moderate concentra tions (> 1 mu M) strychnine nonselectively antagonised both glycine- a nd GABA-evoked currents. At low concentrations (less than or equal to 1 mu M) strychnine blocked glycine-mediated currents but had little ef fect on GABA-mediated currents. Similarly, picrotoxin was a nonselecti ve antagonist for glycine- and GABA-mediated currents at high concentr ations (100 mu M), but was selective for GABA at low concentrations (1 0 mu M). Bicuculline at moderate concentrations (3-10 mu M) had no eff ect on glycine-mediated currents but blocked GABA-evoked currents. 5. These results suggest that glycine and GABA activate different inhibit ory amino acid receptors and that glycine as well as GABA may contribu te to synaptic inhibition in the olfactory bulb.