Neocortical somatostatin neurons reversibly silence excitatory transmission via GABAb receptors.

Understanding the dynamic range for excitatory transmission is a critical component of building a functional circuit diagram for the mammalian brain. Excitatory synaptic transmission is typically studied under optimized conditions, when background activity in the network is low. The range of synaptic function in the presence of inhibitory and excitatory activity within the neocortical circuit is unknown. Paired-cell recordings from pyramidal neurons in acute brain slices of mouse somatosensory cortex show that excitatory synaptic transmission is markedly suppressed during spontaneous network activity: EPSP amplitudes are 2-fold smaller and failure rates are greater than 50%. This suppression is mediated by tonic activation of presynaptic GABAb receptors gated by the spontaneous activity of somatostatin-expressing (Sst) interneurons. Optogenetic suppression of Sst neuron firing was sufficient to enhance EPSP amplitude and reduce failure rates, effects that were fully reversible and occluded by GABAb antagonists. These data indicate that Sst interneurons can rapidly and reversibly silence excitatory synaptic connections through the regulation of presynaptic release. This is an unanticipated role for Sst interneurons, which have been assigned a role only in fast GABAa-mediated inhibition. Because Sst interneuron activity has been shown to be regulated by sensory and motor input, these results suggest a mechanism by which functional connectivity and synaptic plasticity could be gated in a state-dependent manner.