EFFECTS OF GABA(A) INHIBITION ON THE EXPRESSION OF LONG-TERM POTENTIATION IN CA1 PYRAMIDAL CELLS ARE DEPENDENT ON TETANIZATION PARAMETERS

Long-term potentiation (LTP) of excitatory synaptic responses of princ ipal neurons in the hippocampus is accompanied by changes in GABAergic inhibition mediated by interneurons. The impact of inhibition on LTP of excitatory postsynaptic responses in CA1 pyramidal cells was assess ed by monitoring changes in field potentials evoked by Schaffer collat eral stimulation in hippocampal slices in vitro. First, to determine t he effect of inhibition on population EPSPs, slices were exposed to th e GABAA receptor antagonist bicuculline (10 mu M). Both the slope and amplitude of field EPSPs (fEPSPs) were significantly enhanced by bicuc ulline indicating that inhibition modulates excitatory postsynaptic re sponses of pyramidal cells. To assess ii stimulation-dependent changes in inhibition influence LTP of excitatory responses of pyramidal cell s, LTP was examined in the presence and absence of bicuculline (20 mu M) following either 100 Hz tetanization, or theta-patterned stimulatio n (short bursts delivered at 5 Hz). In normal medium, 100 Hz stimulati on produced marked short-term potentiation that decayed 5-10 min post- tetanus and both stimulation paradigms produced similar LTP at 30 min post-tetanus. In comparison, LTP of the fEPSP slope and amplitude was significantly enhanced after theta-patterned stimulation, but not afte r 100 Hz stimulation, in bicuculline. The greater potentiation of fiel d responses following theta-patterned stimulation in the presence of b icuculline indicates that a larger potentiation of excitatory response s was unmasked during suppression of inhibitory inputs. These results suggest that a long-lasting enhancement of inhibition in pyramidal cel ls was also induced following theta-patterned stimulation in normal AC SF. Since suppression of inhibition did not uncover a significantly la rger potentiation following 100 Hz tetanization, the influence of inhi bition on LTP of excitatory responses appears to be stimulation-depend ent. In conclusion, theta-patterned stimulation appears to be more eff ective at inducing plasticity within inhibitory circuits, and this pla sticity may partially offset concurrent increases in the excitability of the CA1 network. Hippocampus 1998;8:289-298. (C) 1998 Wiley-Liss, I nc.