Abstract
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.
Data availability
The datasets generated during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
Special thanks to Joanne Steinmiller and Rachel Bouchard for expert management of transgenic mice, Sarah Bernhard for SAT cage design and technical support, Ajit Ray and Alex Hsu for custom MatLab scripts for behavioral analysis, and members of the Barth Lab for helpful comments on the manuscript.
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This work was supported by NIH 1R01NS088958-01 (ALB), 1RF1MH114103-01 (ALB), T32 NS086749 (DAK), F30 MH118865 (SEM), and the Carnegie Graduate Student Fellowship (EP).
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EP, DAK, SEM, and JAC acquired and analyzed electrophysiological and behavioral data. Experimental design and data interpretation were performed by EP, DAK, and ALB. EP, DAK, JAC, and ALB contributed to writing the manuscript.
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Park, E., Kuljis, D., Myal, S. et al. Sexually dimorphic plasticity of PV inhibition in sensory neocortex during learning. Sci Rep (2026). https://doi.org/10.1038/s41598-025-34400-w
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DOI: https://doi.org/10.1038/s41598-025-34400-w