Long-term potentiation induced by single volley activation: a mechanism for bicuculline-induced enhancement of synaptic field potentials in the CA1 hippocampal region

Abstract

Long-term potentiation in the CA1 region is often evaluated as the change in the initial slope of the field response following a single test stimulus. This change is thought to represent an alteration of excitatory transmission only. However, it has recently been reported that this initial part of the field response is also controlled by a picrotoxin-resistant GABA Aergic response since bicuculline (100 μM), in the presence of picrotoxin, could lead to a substantial increase in the field response initial slope. A disinhibition may then be an important factor underlying expression of what is believed to be long-term potentiation of excitatory synaptic transmission. Alternatively, the bicuculline-induced field response enhancement could be due to an induction of long-term potentiation favoured by the low magnesium (1.25 mM) and high calcium (4 mM) concentrations used in these experiments. Results presented here show that neither picrotoxin (100 μM), nor bicuculline (100 μM), produce any significant change in field response initial slope, when examined using 4 mM magnesium and calcium in the perfusion fluid. In experiments using lower magnesium (1–1.5 mM), the same result was observed in most cases. In some cases, the field response following single test stimuli became temporally paired with spontaneous bursts of spike activity, and its initial slope became considerably enhanced (>100%). Similar results could be provoked by a temporary increase in stimulus strength sufficient to evoke spike activity. This potentiation occluded a subsequent long-term potentiation induced by afferent tetanization, and it was not observed when a N-methyl- d-aspartate receptor antagonist was present in the perfusion solution. The present results suggest that the bicuculline-induced enhancement of the field response initial slope represents an induction of long-term potentiation rather than being a direct consequence of pharmacological blockade of a GABA Aergic process.