Abstract
Preterm birth is a leading risk factor for atypicalities in cognitive and sensory processing, but it is unclear how prematurity impacts circuits that support these functions. To address this, we trained adult male and female mice born a day early (preterm mice) on a visual discrimination task and found that they fail to achieve high levels of performance due to increased responding to the non-rewarded cue. The representation of the non-rewarded cue in the prefrontal cortex (PFC), a brain area that mediates response inhibition, is significantly weaker in regular spiking, putative pyramidal neurons in preterm mice, while their fast-spiking interneurons show blunted responses to both task cues. Similar cue representation is present in the PFC of adolescent term-born mice, suggesting that preterm birth disrupts prefrontal maturation. Altogether, our study describes the long-term impact of preterm birth on prefrontal circuits and highlights their sensitivity to traumatic experiences during the perinatal period.
Data availability
Data associated with figures is provided in the Source Data file. All raw data can be obtained by contacting the corresponding author. Source data are provided with this paper.
Code availability
All analysis codes used in this study are available online (CED website) under https://ced.co.uk/downloads/scriptspkexpr.
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Acknowledgements
This study was supported by the Department of Psychology at the University of Virginia, the National Center For Advancing Translational Sciences of the National Institutes of Health under Award Numbers KL2TR003016/ULTR003015, the Brain Institute at the University of Virginia, Owens Family Foundation and R01MH140184 to A.R. L.Y. D. was in part supported by Summer Research Internship Program (SRIP), O.P.B. by the Harrison Undergraduate Research Award, and S.C.F. by the College Council Student Research Grant at the University of Virginia. The authors would like to thank the Cang and Liu labs at the Departments of Biology and Psychology, as well as the Program in Fundamental Neuroscience, for generous access to their confocal microscopes. The authors would like to acknowledge Dr. Francesca Sciaccotta, Fatima Ribic and Alia Minaya for their help with data analysis.
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E.M.M. and A.R. performed all electrophysiological experiments and confocal imaging, and E.M.M. V.P., and A.R. performed all behavioral experiments, with assistance from M.F., L.Y.D., O.B., S.F., J.S., L.E., T.D.H., and P. A.-A. All authors contributed to the analysis of the behavioral data. Electrophysiological data were analyzed by X.T. and A.R. A.R. conceived the study and wrote the manuscript with input from all authors. All authors of this study have fulfilled the criteria for authorship required by Nature Portfolio journals, as their participation was essential for the design and implementation of the study.
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McCoy, E.M., Pendala, V., Fariborzi, M. et al. Divergent representation and processing of task cues in sensory and prefrontal cortices of preterm-born mice. Nat Commun (2026). https://doi.org/10.1038/s41467-026-68948-6
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DOI: https://doi.org/10.1038/s41467-026-68948-6
