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Sexually dimorphic plasticity of PV inhibition in sensory neocortex during learning
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  • Published: 10 January 2026

Sexually dimorphic plasticity of PV inhibition in sensory neocortex during learning

  • Eunsol Park1,
  • Dika A. Kuljis1,
  • Stephanie E. Myal2,
  • Joseph A. Christian1 &
  • …
  • Alison L. Barth1 

Scientific Reports , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Neuroscience
  • Physiology

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.

Funding

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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Authors and Affiliations

  1. Department of Biological Sciences and Center for the Neural Basis of Cognition, Carnegie Mellon University, 4400 Fifth Ave., Pittsburgh, PA, 15232, USA

    Eunsol Park, Dika A. Kuljis, Joseph A. Christian & Alison L. Barth

  2. Department of Psychiatry, University of Pittsburgh, 200 South Craig Street, Pittsburgh, PA, 15260, USA

    Stephanie E. Myal

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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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Correspondence to Alison L. Barth.

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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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  • Received: 15 August 2025

  • Accepted: 29 December 2025

  • Published: 10 January 2026

  • DOI: https://doi.org/10.1038/s41598-025-34400-w

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Keywords

  • PV neurons
  • Learning
  • Disinhibition
  • Inhibitory synaptic plasticity
  • Sexual dimorphism
  • Sensory cortex
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