Somatostatin contributes to long-term potentiation at excitatory synapses onto hippocampal somatostatinergic...

Somatostatin-expressing interneurons (SOM-INs) are a major subpopulation of GABAergic cells in CA1 hippocampus that receive excitation from pyramidal cells (PCs), and, in turn, provide feedback inhibition onto PC dendrites. Excitatory synapses onto SOM-INs show a Hebbian long-term potentiation (LTP) mediated by type 1a metabotropic glutamate receptors (mGluR1a) that is implicated in hippocampus-dependent learning. The neuropeptide somatostatin (SST) is also critical for hippocampal long-term synaptic plasticity, as well as learning and memory. SST effects on hippocampal PCs are well documented, but its actions on inhibitory interneurons remain largely undetermined. In the present work, we investigate the involvement of SST in long-term potentiation of CA1 SOM-IN excitatory synapses using pharmacological approaches targeting the somatostatinergic system and whole cell recordings in slices from transgenic mice expressing eYFP in SOM-INs. We report that application of exogenous SST₁₄ induces long-term potentiation of excitatory postsynaptic potentials in SOM-INs via somatostatin type 1-5 receptors (SST_1-5Rs) but does not affect synapses of PC or parvalbumin-expressing interneurons. Hebbian LTP in SOM-INs was prevented by inhibition of SSTRs and by depletion of SST by cysteamine treatment, suggesting a critical role of endogenous SST in LTP. LTP of SOM-IN excitatory synapses induced by SST₁₄ was independent of NMDAR and mGluR1a, activity-dependent, and prevented by blocking GABA_A receptor function. Our results indicate that endogenous SST may contribute to Hebbian LTP at excitatory synapses of SOM-INs by controlling GABA_A inhibition, uncovering a novel role for SST in regulating long-term synaptic plasticity in somatostatinergic cells that may be important for hippocampus-dependent memory processes.