Paradoxical enhancement by bicuculline of dentate granule cell IPSPs evoked by fimbria stimulation in rat hippocampal slices.

Stimulation of the fimbria in rat hippocampal slices evoked an extracellular negativity in the granule cell layer and a small depolarization in granule cells at their resting potentials. The intracellular potentials appeared to be GABAA receptor-mediated IPSPs because they reversed at -69.1 +/- 1.0 mV (mean +/- S.E.M., n = 14) and were blocked by the GABAA receptor antagonist bicuculline (10-50 microM, n = 14). However, during the first few minutes of perfusion with bicuculline, IPSPs transiently and paradoxically increased in amplitude. As IPSPs increased, the reversal potential and latency to onset remained the same. These effects were reversible, and during the wash period IPSPs first increased and then stabilized at a smaller amplitude, similar to IPSPs evoked in control conditions. As the GABAA receptor-mediated IPSP decreased, it was followed by a second hyperpolarization. This late hyperpolarization appeared to be a GABAB receptor-mediated IPSP, because it reversed near the equilibrium potential for potassium (mean -81.8 +/- 2.3 mV, n = 12, [K+]o = 5 mM) and was blocked by the GABAB receptor antagonist 2-hydroxy saclofen (250-500 microM, n = 5). The results suggest that GABAA and GABAB receptor-mediated IPSPs evoked in granule cells by fimbria stimulation are normally inhibited by activation of GABAA receptors. The inhibition by GABAA receptors is strong enough that, in control conditions, the GABAA IPSPs are barely detectable and the GABAB IPSPs are undetectable.(ABSTRACT TRUNCATED AT 250 WORDS)