GABAERGIC CONTROL OF ODOR-INDUCED ACTIVITY IN THE FROG OLFACTORY-BULB- POSSIBLE GABAERGIC MODULATION OF GRANULE CELL INHIBITORY-ACTION

In the olfactory bulb, the activity of the output neurons, the mitral cells, is under inhibitory control exerted by GABAergic interneurons, the granule cells. Although the mechanisms of this inhibition are well known from in vitro studies, its physiological role in controlling mi tral cell activity in response to odours has never been investigated. This study planned to improve understanding of the involvement of gran ule cells. To do so, GABA(A)-synaptic mechanisms were altered using GA BA(A) antagonists in order to observe the consequences on mitral cell electrophysiological responses to odours, delivered over a wide concen tration range. Due to the laminar organization of bulbar cell populati ons, the antagonists picrotoxin or bicuculline were injected into the bulbar ventricle in order to block granule cell inhibitory action at f irst. Surprisingly, the early consequence of the antagonist injection was a decrease in cell responsivity: response spike frequencies were l owered while thresholds were occasionally shifted toward higher concen trations. This initial depressive effect was followed by a recovery of control excitability and, later, by an increase in excitability: spik e bursts became more sustained in frequency and in duration. At the sa me time, in most of the cells studied, spontaneous activity became bur sting. The early depressive effect of GABA(A) antagonists is discussed in terms of an enhancement of the inhibitory influence of granule cel ls on mitral cells. This might reflect a blocking action of the antago nists at the level of GABAergic synapses located on granule cells them selves. The late effect, an increase in excitability, is explained as the consequence of the alteration of the functioning of dendrodendriti c synapses between granule and mitral cells leading to a disinhibition of the latter. The comparison of the present findings with others obt ained when antagonists were applied on to glomerular layers led us to infer that granule cell inhibition would be devoted to limiting mitral cell responses in frequency and in duration rather than to adjusting their response threshold. The chronology of the effects observed stron gly supports the fact that, following the intraventricular injection, the antagonists acted primarily in the deep layers of the bulb. Nevert heless, due to free diffusion starting from the injection site, the po ssibility that drugs act later in the glomerular layer can not be reje cted. It can be concluded that, in addition to its extensive involveme nt through intrinsic interneurons, GABA might also control the strengt h of the inhibition exerted by granule cells on mitral cells via centr ifugal fibres.