Somatostatin neurons detect stimulus-reward contingencies to reduce neocortical inhibition during learning.

Learning involves the association of discrete events in the world to infer causality, likely through a cascade of changes at input- and target-specific synapses. Transient or sustained disinhibition may initiate cortical circuit plasticity important for association learning, but the cellular networks involved have not been well defined. Using recordings in acute brain slices, we show that whisker-dependent sensory association learning drives a durable, target-specific reduction in inhibition from somatostatin (SST)-expressing GABAergic neurons onto pyramidal (Pyr) neurons in superficial but not deep layers of mouse somatosensory cortex. Critically, SST output was not altered when stimuli and rewards were unpaired, indicating that these neurons are sensitive to stimulus-reward contingency. Depression of SST output onto Pyr neurons could be phenocopied by chemogenetic suppression of SST activity outside of the training context. Thus, neocortical SST neuron output can undergo long-lasting modifications to selectively disinhibit superficial layers of sensory neocortex during learning.