NOVEL GLUTAMATE-INDEPENDENT AND GABA-INDEPENDENT SYNAPTIC DEPOLARIZATION IN GRANULE CELLS OF GUINEA-PIG HIPPOCAMPUS

1. Dual intracellular recordings of granule cells, hilar interneurons and CA3 pyramidal cells were performed in transverse slices of guinea- pig hippocampus. At resting membrane potential, in the presence of 4-a minopyridine, ionotropic glutamate receptor antagonists and the GABA(A ) receptor antagonist bicuculline, granule cells showed spontaneous, l arge amplitude depolarizations correlated with synchronous bursting ac tivity of interneurons. 2. Under these conditions, pyramidal cells exh ibited large amplitude monophasic GABA(B) inhibitory postsynaptic pote ntials (IPSPs) synchronous with the GABAergic interneuron burst discha rges. The granule cells also received a GABA(B) input, which was evide nt only when the neurons were depolarized by DC injection. The GABA(B) receptor antagonist CGP 55845A (CGP) blocked the GABA(B) IPSPs in bot h pyramidal cells and granule cells; however, the depolarizing potenti al in granule cells was unaffected by the drug. 3. The granule cell de polarization in the presence of CGP was monophasic and exhibited linea r voltage dependence with a reversal potential around -40 mV, suggesti ng that it was generated by a synaptic input activating a mixed cation ic current. 4. The granule cell depolarization was abolished following the addition of tetrodotoxin to the bath. In addition, perfusing the slice with a low Ca2+-containing solution (0.5 mM Ca2+ - 10 mM Mg2+) a lso abolished the granule cell depolarization, confirming the synaptic origin of the event. 5. (S)-Methyl-4-carboxyphenylglycine, L-(+)-2-am ino-3-phosphonopropionic acid, propranolol and atropine did not affect the granule cell depolarization, indicating that metabotropic glutama te receptor's, beta-adrenergic receptors and muscarinic cholinergic re ceptors were not involved in generating tile granule cell depolarizing synaptic response. 6. These findings indicate that, in the absence of both glutamatergic and GABAergic inputs, synchronous interneuronal ac tivity can produce a depolarizing synaptic response in granule cells. The neurochemical responsible for the depolarization is currently unde r investigation.