Functional effects of somatostatin receptor 1 activation on synaptic transmission in the mouse hippocampus

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 (sst 1 -sst 5 ) in mediating SRIF action requires some clarification. We used hippocampal slices of wild-type and sst 1 knockout (KO) mice and selective pharmacological tools to provide conclusive evidence for a role of sst 1 in mediating SRIF inhibition of synaptic transmission. With single-and double-label immunohistochemistry, we determined the distribution of sst 1 in hippocampal slices and we quantified sst 1 colocalization with SRIF. With electrophysiology, we found that sst 1 activation with CH-275 inhibited both the NMDA-and the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-mediated responses. Results from sst 1 KO slices confirmed the specificity of CH-275 effects; sst 1 activation did not affect the inhibitory transmission which was in contrast increased by sst 4 activation with L-803,087 in both wild-type and sst 1 KO slices. The AMPA-mediated responses were increased by L-803,087. Functional interaction between sst 1 and sst 4 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 sst 1 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 sst 1 may represent an important contribution to the regulation of hippocampal activity.

Cortistatin‐14 Mediates its Anticonvulsant Effects Via sst2 and sst3 but Not Ghrelin Receptors

“…In mice however, contradictory data have been reported. Inhibitory actions were demonstrated for mice sst 1 and sst 4 receptors although other studies report on a minor role of sst 1 receptors and excitatory actions of sst 4 receptors .…”

Vascular endothelial growth factor up‐regulation in the mouse hippocampus and its role in the control of epileptiform activity

“…In the present study, chromatography/tandem mass spectrometry was used to measure glutamate levels in hippocampal slices according to previous studies in the mouse hippocampus (Cammalleri et al. , 2009) and in mouse retinal explants (Catalani et al.…”

“…Hippocampal slices were prepared as previously described (Cammalleri et al. , 2004, 2006, 2009; Ristori et al.…”

“…In additional slices, 0 Mg 2+ /4‐AP was applied in combination with tetrotodoxin (TTX, 0.5 μ m ) to block synaptic activity (Bains et al. , 1999; Cammalleri et al. , 2009).…”

Somatostatinergic systems: an update on brain functions in normal and pathological aging

“…Recent publications suggest that sst 3 and sst 4 (but not sst 1 ; de Bundel et al, 2010) have potent anticonvulsive properties (Aourz et al, 2011), and that sst 2 , the major receptor subtype involved in the anticonvulsant effect of SRIF in the hippocampus exerts a functional cooperation with sst 3 /sst 4 . In hippocampus, sst 1 activation inhibits both NMDA- and AMPA-mediated responses but did not affect the inhibitory transmission (Cammalleri et al, 2009). …”