Somatostatin depresses long-term potentiation and Ca2+ signaling in mouse dentate gyrus.
The selective loss of somatostatin (SST)-containing interneurons from the hilus of the dentate gyrus is a hallmark of epileptic hippocampus. The functional consequence of this loss, including its contribution to postseizure hyperexcitability, remains unclear. We address this issue by characterizing the actions of SST in mouse dentate gyrus using electrophysiological techniques. Although the majority of dentate SST receptors are located in the outer molecular layer adjacent to lateral perforant path (LPP) synapses, we found no consistent action of SST on standard synaptic responses generated at these synapses. However, when SST was present during application of high-frequency trains that normally generate long-term potentiation (LTP), the induction of LTP was impaired. SST did not alter the maintenance of LTP when applied after its induction. To examine the mechanism by which SST inhibits LTP, we recorded from dentate granule cells and examined the actions of this neuropeptide on synaptic transmission and postsynaptic currents. Unlike findings in the CA1 hippocampus, we observed no postsynaptic actions on K(+) currents. Instead, SST inhibited Ca(2+)/Ba(2+) spikes evoked by depolarization. This inhibition was dependent on N-type Ca(2+)currents. Blocking these currents also blocked LTP, suggesting a mechanism through which SST may inhibit LTP. Our results indicate that SST reduction of dendritic Ca(2+) through N-type Ca(2+) channels may contribute to modulation of synaptic plasticity at LPP synapses. Therefore the loss of SST function postseizure could result in abnormal synaptic potentiation that contributes to epileptogenesis.
Baratta
Michael V
MV
Department of Neuropharmacology, The Scripps Research Institute La Jolla, California 92037, USA.
Lamp
Tyra
T
Tallent
Melanie K
MK
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D051379:Mice; D019580:Perforant Pathway / Q000187:drug effects / Q000502:physiology; D013004:Somatostatin / Q000494:pharmacology*
D006728:Hormones; D013004:Somatostatin; D002118:Calcium