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Ethological learning during the critical period resets synaptic setpoints in mouse binocular visual cortex.

Diane Bissen1, Brian A Cary1, Amanda Zhang1

  • 1Department of Biology, Brandeis University, Waltham, MA 02453, USA.

Neuron
|July 15, 2026
PubMed
Summary

Active learning during critical periods reshapes brain circuitry. Prey capture training in mice enhanced visual function by remodeling neural connections, a process dependent on tumor necrosis factor α (TNF-α).

Keywords:
TNF-αcritical perioddendritic spinehomeostatic plasticityprey capture learningtemporal frequency tuningvisual cortex

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Systems Neuroscience

Background:

  • Critical periods are key developmental stages for refining neural circuits.
  • Visual system plasticity during critical periods is well-studied, but the role of active, ethological experiences remains unclear.

Purpose of the Study:

  • To investigate structural and functional plasticity in the visual cortex during a critical period using prey capture learning.
  • To understand how active visual learning impacts neuronal circuitry and behavior.

Main Methods:

  • Utilized prey capture learning paradigm in critical-period mice.
  • Assessed structural plasticity via dendritic spine dynamics (turnover and density).
  • Measured functional plasticity through temporal frequency discrimination and identified the role of tumor necrosis factor α (TNF-α).

Main Results:

  • Prey capture learning significantly improved temporal frequency discrimination.
  • Visual learning induced widespread and persistent remodeling of visual circuitry, including increased spine turnover and altered spine density.
  • This experience-dependent plasticity was specific to the critical period and absent in adult mice.
  • Tumor necrosis factor α (TNF-α)-dependent homeostatic plasticity was crucial for behavioral improvement.

Conclusions:

  • Ethological experiences during critical periods drive significant synaptic remodeling in the visual cortex.
  • Homeostatic plasticity mechanisms, involving TNF-α, are co-opted to enable this widespread rewiring.
  • This remodeling supports enhanced visual function and adaptive behavior, highlighting the importance of active interaction with the environment during development.