Sexually dimorphic plasticity of PV inhibition in sensory neocortex during learning

Neocortical parvalbumin-expressing (PV) neurons critically regulate circuit excitation by strong synaptic inputs onto local pyramidal (Pyr) neurons. Plasticity in PV-mediated inhibition during learning could have pronounced effects on gating excitatory synaptic plasticity and circuit excitability, but experimental evidence to support this input- and target-specific plasticity is scant. Here, we used in vitro electrophysiology to determine whether training in a whisker-based sensory-association task could alter PV-mediated inhibition in the primary somatosensory cortex of mice. Using light-evoked activation of channelrhodopsin-expressing PV neurons, we found that evoked PV-IPSCs in Pyr neurons from layer (L) 2/3, but not L5, were rapidly suppressed at the onset of training. This reduction was sex-specific, occurring only in females. Notably, when whisker stimulation was decoupled from the water reward during pseudotraining, PV-mediated inhibition remained stable. Thus, reduced PV inhibition in superficial layers is an early response to the development of stimulus-reward associations during sensory learning. In addition, these data underscore the importance of including sex as a biological variable in studies of learning-related cortical plasticity.