Functional effect of somatostatin receptor 1 activation on synaptic transmission in the mouse hyppocampus

Abstract

Somatostatin-14 (SRIF) co-localizes with GABA in the hippocampus and regulates neuronal excitability. A role of SRIF in the control of hippocampal activity has been proposed, although the exact contribution of each SRIF receptor (sst1– sst5) in mediating SRIF action requires some clarification. We used hippocampal slices of wild-type and sst1 knockout (KO) mice and selective pharmacological tools to provide conclusive evidence for a role of sst1 in mediating SRIF inhibition of synaptic transmission. With single- and double-label immunohistochemistry, we determined the distribution of sst1 in hippocampal slices and we quantified sst1 colocalization with SRIF. With electrophysiology, we found that sst1 activation with CH-275 inhibited both the NMDA- and the a-amino- 3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-mediated responses. Results from sst1 KO slices confirmed the specificity of CH-275 effects; sst1 activation did not affect the inhibitory transmission which was in contrast increased by sst4 activation with L-803,087 in both wild-type and sst1 KO slices. The AMPA-mediated responses were increased by L-803,087. Functional interaction between sst1 and sst4 is suggested by the finding that their combined activation prevented the CH-275-induced inhibition of AMPA transmission. The involvement of pre-synaptic mechanisms in mediating inhibitory effects of sst1 on excitatory transmission was demonstrated by the finding that CH-275 (i) increased the paired-pulse facilitation ratio, (ii) did not influence the AMPA depolarization in the presence of tetrodotoxin, and (iii) inhibited glutamate release induced by epileptiform treatment. We conclude that SRIF control of excitatory transmission through an action at sst1 may represent an important contribution to the regulation of hippocampal activity.