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Updated: Jan 15, 2026

A Fully Automated Rodent Conditioning Protocol for Sensorimotor Integration and Cognitive Control Experiments
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Evolutionary consideration of serial order processing by the normal rodent brain.

Veronika Zlatkina1, Katherine Martakis1, Houman Azizi1,2

  • 1Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.

Proceedings of the National Academy of Sciences of the United States of America
|October 6, 2025
PubMed
Summary

Rodents can process directional sequences but struggle with random ones, unlike primates with advanced prefrontal cortex. This highlights the executive control limits in rodent working memory for complex serial order tasks.

Keywords:
prefrontal cortexrodent brainserial order processingworking memory

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Area of Science:

  • Neuroscience
  • Comparative Psychology
  • Cognitive Science

Background:

  • The primate prefrontal cortex evolved from an older agranular form to a granular mid-dorsolateral region.
  • Rodent brains possess only the agranular stage, termed medial prefrontal cortex.
  • The granular prefrontal cortex is crucial for monitoring working memory, including precise serial order processing.

Purpose of the Study:

  • To investigate the functional limitations of serial order processing in the rodent brain.
  • To compare serial order processing capabilities between rodents and primates based on prefrontal cortex evolution.

Main Methods:

  • Assessed normal rats' ability to monitor the serial order of spatial stimuli (locations).
  • Tested processing of both directional (left-to-right, right-to-left) and nondirectional (randomly varying) sequences.

Main Results:

  • Rodents accurately coded the serial order of directional location sequences.
  • Serial order processing of nondirectional sequences was limited, relying on recent stimuli for approximate order.
  • Performance degraded significantly with random sequences, indicating limited executive control for precise order coding.

Conclusions:

  • The rodent brain has functional limits in processing complex serial order, especially nondirectional sequences.
  • The evolution of the granular prefrontal cortex in primates provides enhanced executive control for precise working memory manipulation.
  • This difference underscores the role of advanced prefrontal cortex development in complex cognitive functions like action planning.