EN
Disynaptic inhibition through somatostatin (SST) interneurons is a powerful potential mechanism for gain control in cortical circuits. However, excitatory drive to SST neurons is remarkably weak. Here we investigate the modulation of local pyramidal (Pyr) inputs onto SST interneurons of layer 2/3 in mouse barrel cortex, using in vitro and in vivo whole-cell recordings from Pyr-SST pairs with a combination of pharmacological screening and optogenetic activation of specific modulatory pathways. We show that presynaptic nicotinic acetylcholine receptor activation rapidly enhances local excitatory inputs onto SST neurons through PKA-dependent pathway. Precisely-timed, brief optogenetic activation of cholinergic fibers was sufficient to account for the enhancement of synaptic efficacy induced by pharmacological activation of Ach receptors. Importantly, these effects were synapse‑specific and did not occur at local excitatory connections between pyramidal neurons, indicating that cholinergic fibers selectively modulate synaptic transmission toward enhanced SST neurons-mediated inhibition. Our results show that brain state can selectively alter network function through the input‑specific modulation of specific synaptic motifs. FINANCIAL SUPPORT: This work was supported by the McKnight Foundation (ALB) and NIH R01NS088958 (ALB and JFAP), the National Science Centre, Poland (2015/18/E/ NZ4/00721; JUC), the European Research council (ERC-2015-CoG-682422; JFAP), the DFG (DFG-FOR-2143-Interneuron; JFAP), the Berlin Institute of Health (BIH; JFAP) and the European Union (FP7, 3x3Dimaging 323945; JFAP).