SOMATOSTATIN DEPRESSES EXCITATORY BUT NOT INHIBITORY NEUROTRANSMISSION IN RAT CA1 HIPPOCAMPUS

In rat CA1 hippocampal pyramidal neurons (HPNs), somatostatin (SST) ha s inhibitory postsynaptic actions, including hyperpolarization of the membrane at rest and augmentation of the K+ M-current. However, the ef fects of SST on synaptic transmission in this brain region have not be en well-characterized. Therefore we used intracellular voltage-clamp r ecordings in rat hippocampal slices to assess the effects of SST on ph armacologically isolated synaptic currents in HPNs. SST depressed both pha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)/kainat e and N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsyn aptic currents (EPSCs) in a reversible manner, with an apparent IC50 o f 22 nM and a maximal effect at 100 nM. In contrast, SST at concentrat ions up to 5 mu M had no direct effects on either gamma-aminobutyric a cid-A (GABA(A)) or GABA(B) receptor-mediated inhibitory postsynaptic c urrents (IPSCs). The depression of EPSCs by SST was especially robust during hyperexcited states when polysynaptic EPSCs were present, sugge sting that this peptide could play a compensatory role during seizurel ike activity. SST effects were greatly attenuated by the alkylating ag ent N-ethylmaleimide, thus implicating a transduction mechanism involv ing the G(i)/G(o) family of G-proteins. Use of 2 M Cs+ in the recordin g electrode blocked the postsynaptic modulation of K+ currents by SST, but did not alter the effects of SST on EPSCs, indicating that postsy naptic K+ currents are not involved in this action of SST. However, 2 mM external Ba2+ blocked the effect of SST on EPSCs, suggesting that p resynaptic K+ channels or other presynaptic mechanisms may be involved . These findings and previous results from our laboratory show that SS T has multiple inhibitory effects in hippocampus.