Abstracts

RATIONALE: Somatostatin (SST)-containing interneurons in the hilus of the dentate gyrus are exquisitely vulnerable to seizure-induced death. The consequences of this neuronal loss are poorly understood, as the function of these neurons remains unclear. One result of this cell death would be the loss of SST function in the dentate. Understanding the role of SST in the dentate could therefore provide insight into the development of excessive hippocampal excitability seen post-seizure. METHODS: We used the mouse (C57BL/6) horizontal hippocampal slice preparation to record excitatory postsynaptic potentials (EPSPs) extracellularly in the outer molecular layer and intracellularly in dentate granule cells of ventral hippocampus. SST was bath applied for 10-15 min. Synaptic plasticity was examined by giving high frequency trains of stimuli to induce long-term potentiation (LTP), a long-lasting enhancement of synaptic responses likely involved in learning, memory, and epileptogenesis. RESULTS: Normal EPSPs generated in standard extracellular medium were unaltered by SST. However, SST reversibly inhibited NMDA receptor-mediated EPSPs isolated in low magnesium by blocking AMPA receptors. In the presence of SST, short-term potentiation immediately following the high frequency trains was present, but LTP was greatly reduced. CONCLUSIONS: SST does not appear to regulate standard synaptic transmission at perforant path/dentate granule cell synapses. However, when NMDA-mediated responses are uncovered, SST has an inhibitory effect. Further, SST depresses synaptic facilitation caused by high-frequency trains of stimuli, possibly via its inhibition of NMDA-receptor mediated responses. Since NMDA receptors are critical for somes types of epileptogenesis in dentate, SST may have an important function in selectively reducing synaptic events associated with hyperexcitability. These results suggest that the loss of SST function could contribute to the increased the vulnerability of epileptic hippocampus to invasion by seizure events.[Supported by NINDS grant NS 38633]