Emergence of cortical inhibition by coordinated sensory–driven plasticity at distinct synaptic loci

Feed–forward GABAergic inhibition sets dendritic integration window thereby controlling timing and output in cortical circuits. However, it is unclear how feed–forward inhibitory circuits emerge, even though this is a critical step for neocortical development and function. Here we show that sensory–experience drives plasticity of the feed–forward inhibitory circuit in mouse layer 4 somatosensory “barrel” cortex in the second postnatal week by two distinct mechanisms. Firstly, sensory–experience selectively strengthens thalamocortical to feed–forward interneuron inputs via a presynaptic mechanism, but does not regulate other inhibitory circuit components. Secondly, experience drives a postsynaptic mechanism in which a down–regulation of a prominent thalamocortical NMDA EPSP in stellate cells regulates final expression of functional feed–forward inhibitory input. Thus, experience is required for specific, coordinated changes at thalamocortical synapses onto both inhibitory and excitatory neurons producing a circuit plasticity that results in maturation of functional feed–forward inhibition in layer 4.