The Locomoting State Selectively Amplifies Activity of Sensitizing Neurons in Primary Visual Cortex

Sensory processing in the cortex reflects both adaptation to external stimuli and changes in internal state. To investigate how these processes interact in layer 2/3 of mouse V1 we combined calcium imaging, optogenetics and circuit modelling. We find that locomotion preferentially increases gain in pyramidal cells (PCs) that sensitize during visual stimulation compared to those that depress. A model explains this differential modulation through three mechanisms: (i) variations in the strength of PV and SST connectivity to individual PCs, (ii) broad locomotion-dependent weakening of PC and PV synapses, and (iii) reduced SST inhibition targeting sensitizing PCs. These results demonstrate that behavioural state selectively shifts cortical computation toward distinct adaptive regimes. The apparently paradoxical combination of increased PC gain but decreased synaptic strength is consistent with a state-dependent gating mechanism that boosts signals leaving V1 while simultaneously preventing disruption of the local excitatory-inhibitory balance required for stable computation.