Cell-type specific effects of somatostatin on synaptic transmission in the anterior cingulate cortex.

Inhibitory modulation of glutamatergic information processing is a prerequisite for proper network function. Among the many groups of interneurons, somatostatin-expressing interneurons (SOM-INs) play an important role in the maintenance of physiological brain activity. We have previously shown that somatostatin (SOM) causes a reduction in pyramidal cell (PC) excitability. However, the mechanisms of action of the peptide on cortical synaptic circuits are still unclear. To understand the effects of the neuropeptide SOM on cortical synaptic circuits, we performed a detailed side-by-side comparison of its postsynaptic effects on PCs, SOM-INs and layer 1 interneurons (L1-INs) in the anterior cingulate cortex of male and female mice and found that SOM produced pronounced postsynaptic effects in PCs while having little to no effect on either IN type. This comparison allowed us to link the observed postsynaptic effects to SOM-induced modulations of glutamatergic and GABAergic synaptic transmission and to trace the impact of the neuropeptide on the neuronal circuitry between these 3 cell types. We show here that SOM depresses glutamatergic synaptic transmission via a presynaptic mechanism while exerting a differential impact on GABAA receptor (GABAAR)- and GABAB receptor (GABABR)-mediated synaptic transmission at the pre- and postsynaptic level resulting in a shift of inhibition in L2/3 PCs from L1-INs to SOM-INs. In summary, this study unravels a novel aspect by which SOM modulates synaptic signaling between PCs, L1-INs and SOM-INs.Significance Statement Somatostatin-expressing interneurons represent a distinct class of GABAergic interneurons whose main function is a modulation of top-down inputs into the cortex. Despite a large body of evidence investigating behavior-specific activity of SOM-INs within the cortex, our understanding of the nature of SOM-IN-mediated modulation of synaptic transmission remains limited. Specifically, the function of the secreted neuropeptide within cortical circuits is not understood. By analyzing the effect of SOM not only on pyramidal cells but also on GABAergic INs, the study presented here provides detailed insight into the pre- and postsynaptic mechanisms of SOM in modulating local and distant information flow.