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In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
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An Operant Intra-/Extra-dimensional Set-shift Task for Mice
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Sex-biased computations underlying differential set shift performance in mice.

Nic Glewwe1, Evan M Dastin-van Rijn2, Cathy S Chen3

  • 1Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
|April 10, 2026
PubMed
Summary
This summary is machine-generated.

Female mice exhibit superior cognitive flexibility compared to males, demonstrating faster learning and quicker decision-making after rule shifts. This sex difference in cognitive flexibility may offer insights into neuropsychiatric conditions.

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Area of Science:

  • Neuroscience
  • Behavioral Science
  • Computational Psychiatry

Background:

  • Cognitive flexibility, the ability to adapt strategies based on feedback, is crucial for adaptive behavior.
  • Disruptions in cognitive flexibility are observed in various neuropsychiatric disorders.
  • Individual differences in cognitive flexibility may underlie risk and resilience in these conditions.

Purpose of the Study:

  • To investigate sex-based differences in cognitive flexibility in mice.
  • To identify computational mechanisms underlying these sex differences.
  • To explore the relationship between sex, cognitive flexibility, and neuropsychiatric risk.

Main Methods:

  • Development of a novel touchscreen Set Shift task for continuous mouse testing.
  • Behavioral assessment of rule shifting performance in male and female mice.
  • Application of computational models to analyze individual differences in cognitive computations.

Main Results:

  • Female mice demonstrated significantly enhanced cognitive flexibility, completing more rule shifts with fewer errors than males.
  • Computational models revealed sex-biased differences in learning and decision-making processes post-rule shift.
  • Female mice exhibited faster rule acquisition and earlier commitment to choices, potentially by processing multiple rules concurrently.

Conclusions:

  • Sex is a significant factor influencing cognitive flexibility and its underlying computations in mice.
  • Enhanced choice stability in females contributes to superior cognitive flexibility in the Set Shift task.
  • Findings suggest potential sex-specific mechanisms relevant to neuropsychiatric disorders.