Higher-order thalamocortical inputs gate synaptic long-term potentiation via disinhibiton

Sensory experience and perceptual learning changes the receptive field properties of cortical pyramidal neurons, largely mediated by long-term potentiation (LTP) of synapses. The circuit mechanisms underlying cortical LTP remain unclear. In the mouse somatosensory cortex (S1), LTP can be elicited in layer (L) 2/3 pyramidal neurons by rhythmic whisker stimulation. We combined electrophysiology, optogenetics, and chemogenetics in thalamocortical slices to dissect the synaptic circuitry underlying this LTP. We found that projections from higher-order, posteriormedial thalamic complex (POm) to S1 are key to eliciting NMDAR-dependent LTP of intracortical synapses. Paired activation of intracortical and higher-order thalamocortical pathways increased vasoactive intestinal peptide (VIP) interneuron and decreased somatostatin (SST) interneuron activity, which was critical for inducing LTP. Our results reveal a novel circuit motif in which higher-order thalamic feedback gates plasticity of intracortical synapses in S1 via disinhibition. This motif may allow contextual feedback to shape synaptic circuits that process first-order sensory information.