SOMATOSTATIN INHIBITS EXCITATORY TRANSMISSION AT RAT HIPPOCAMPAL SYNAPSES VIA PRESYNAPTIC RECEPTORS

Somatostatin is one of the major peptides in interneurons of the hippo campus. It is believed to play a role in memory formation and to reduc e the susceptibility of the hippocampus to seizure-like activity. Howe ver, at the cellular level, the actions of somatostatin on hippocampal neurons are still controversial, ranging from inhibition to excitatio n. In the present study, we measured autaptic currents of hippocampal neurons isolated in single-neuron microcultures. Somatostatin and the analogous peptides seglitide and octreotide reduced glutamatergic, but not GABAergic, autaptic currents via pertussis toxin-sensitive G-prot eins. This effect was observed whether autaptic currents were mediated by NMDA or non-NMDA glutamate receptors. Furthermore, somatostatin di d not affect currents evoked by the direct application of glutamate, b ut reduced the frequency of spontaneously occurring excitatory autapti c currents. These results show that presynaptic somatostatin receptors of the SRIF1 family inhibit glutamate release at hippocampal synapses . Somatostatin, seglitide, and octreotide also reduced the frequency o f miniature excitatory postsynaptic currents in mass cultures without affecting their amplitudes. In addition, all three agonists inhibited voltage-activated Ca2+ currents at neuronal somata, but failed to alte r K+ currents, effects that were also abolished by pertussis toxin. Th us, presynaptic somatostatin receptors in the hippocampus selectively inhibit excitatory transmission via G-proteins of the G(i)/G(o) family and through at least two separate mechanisms, the modulation of Ca2channels and an effect downstream of Ca2+ entry, This presynaptic inhi bition by somatostatin may provide a basis for its reportedly anticonv ulsive action.