Although the peptide somatostatin (SST) has been speculated to function in
temporal lobe epilepsy, its exact role is unclear, as in vivo studies have
suggested both pro- and anticonvulsant properties. We have shown previously
that SST has multiple inhibitory cellular actions in the CAI region of the
hippocampus. suggesting that in this region SST should have antiepileptic
actions To directly assess thr effect of SST on epileptiform activity. we s
tudied two in vitro models of epilepsy in the rat hippocampal slice prepara
tion using extracellular and intracellular recording techniques. In one, GA
BA-mediated neurotransmission was inhibited by superfusion of the GABA, rec
eptor antagonist bicuculline. In the second. we superfused Mg free artifici
al cerebrospinal fluid to remove the Mg2+ block of the N-methyl-D-aspartate
(NMDA) subtype of glutamate receptor, We show here that SSI markedly reduc
es the intensity of evoked epileptiform afterdischarges and the frequency o
f spontaneous bursts in both CA1 and CA3. SST appears to act additively in
the two regions to suppress the transmission of epileptiform events through
the hippocampus. Wt further examined SST's actions in CA? and found that S
ST dramatically reduced the frequency of paroxysmal depolarizing shifts (PD
Ss) recorded intracellularly in current clamp. as well as increasing the th
reshold for evoking ''giant" excitatory postsynaptic currents (EPSCs). larg
e polysynaptically mediated EPSCs that are the voltage-clamp correlate of P
DSs. We also examined the actions of SST on pharmacologically isolated EPSC
s generated at both mossy fiber (MF) and associational/commissural (A/C) sy
napses. SST appears to act specifically to reduce recurrent excitation betw
een CA3 neurons because it depresses A/C-but nut MF-evoked EPSCs. SST also
increased paired-pulse facilitation of A/C EPSCs. suggesting a presynaptic
site of action. Reciprocal activation of CA3 neurons through A/C fibers is
critical for generation of epileptiform activity in hippocampus. Thus SST r
educes feedforward excitation in rat hippocampus. acting to "brake" hyperex
citation. This is a function unique from that described for other hippocamp
al neuropeptides, which affect more standard neurotransmission. Our results
suggest that SST receptors could be a unique, selective clinical target fo
r treatment of limbic seizures.