Modulation of coordinated activity across cortical layers by plasticity of inhibitory synapses onto layer 5 pyramidal neurons

In the neocortex, synaptic inhibition shapes all forms of spontaneous and sensory-evoked activity. Importantly, inhibitory transmission is highly plastic, but the functional role of inhibitory synaptic plasticity is unknown. In the mouse barrel cortex, activation of layer 2/3 PNs elicited strong feed-forward perisomatic inhibition (FFI) onto layer 5 PNs. We found that FFI involving PV cells was strongly potentiated by postsynaptic PN burst firing. FFI plasticity modified PN excitation-to-inhibition (E/I) ratio, strongly modulated PN gain and altered information transfer across cortical layers. Moreover, our LTPi-inducing protocol modified the firing of layer 5 PNs and altered the temporal association of PN spikes to γ-oscillations both in vitro and in vivo. All these effects were captured by unbalancing the E/I ratio in a feed-forward inhibition circuit model. Altogether, our results indicate that activity-dependent modulation of perisomatic inhibitory strength effectively influences the participation of single principal cortical neurons to cognitive-relevant network activity. Impact Statement Long-term potentiation of feed-forward perisomatic inhibition effectively alters the computational properties of single layer 5 pyramidal neurons and their association to network activity.