Bicuculline- and phaclofen-sensitive components of N-methyl-D-aspartate-induced hyperpolarizations in rat dorsolateral septal nucleus neurones.

1. Intracellular recordings were made from rat dorsolateral septal nucleus (DLSN) neurones in vitro. Pressure application (puff) of N-methyl-D-aspartate (NMDA) usually produced a hyperpolarization followed by a depolarization in normal Mg2+ solution. 2. A hyperpolarizing response and a depolarizing response could be evoked separately by appropriate positioning of the puff pipette. The NMDA-induced hyperpolarization was blocked by a low-Ca2+ solution or a tetrodotoxin (TTX)-containing solution, but under these conditions the NMDA-induced depolarization was spared. The amplitude of NMDA-induced hyperpolarizations was 7.7 +/- 2.7 mV (n = 13) at the resting membrane potential level. 3. An NMDA-induced hyperpolarization had two components. A fast component reversed at about -76 mV and a slow component reversed at -90 mV. The reversal potential of the slow component shifted in the depolarizing direction of hyperpolarizing direction when the slice was bathed in a high or low-K+ solution, respectively. 4. The reversal potentials of NMDA-induced hyperpolarizations were similar to the synaptic potentials evoked by fimbrial stimulation. The reversal potentials of the fast and slow components were close to the IPSP reversal potential (-70 mV) and the late hyperpolarizing potential (LHP) reversal potential (-95 mV), respectively. 5. NMDA-induced hyperpolarizations were blocked by the specific NMDA receptor antagonist 2-amino-5-phosphonopontanoate (APV). The fast component of an NMDA-induced hyperpolarization was blocked by the specific GABAA receptor antagonist, bicuculline, and the slow component was depressed by the specific GABAB receptor antagonist, phaclofen. 6. Glutamate receptor subtype-specific agonists, such as kainate or quisqualate, could induce similar hyperpolarizations which had bicuculline-sensitive and insensitive components. These non-NMDA-type agonist-induced hyperpolarizations were not affected by APV (50 microM) but were blocked by kynurenic acid (1 mM). 7. We conclude that these excitatory amino acid-induced hyperpolarizations observed in the rat DLSN are mediated by GABAergic interneurones which have both non-NMDA-type and NMDA-type receptors.