Enrichment-induced forgetting is associated with white matter microstructure in mice

Area of Science:

• Neuroscience
• Neuroplasticity
• Memory Research

Background:

• Memories are stored in brain circuits (engrams) and forgetting occurs when these circuits are not reactivated.
• Neuroplasticity, particularly in grey matter, is known to destabilize memory circuits and contribute to forgetting.
• The role of white matter plasticity in forgetting remains largely unexplored.

Purpose of the Study:

• To investigate the impact of environmental enrichment on white matter plasticity and its relation to forgetting.
• To explore whether changes in white matter tracts contribute to memory loss induced by environmental enrichment.
• To examine the role of myelin-related plasticity in forgetting.

Main Methods:

• Inducing brain plasticity through environmental enrichment (EE) in mice after contextual fear conditioning.
• Assessing forgetting by measuring freezing behavior during fear conditioning tests.
• Utilizing ex vivo brain diffusion-weighted MRI to analyze white matter plasticity (fractional anisotropy).
• Administering clemastine fumarate (a pro-myelinating drug) to investigate its effect on forgetting.
• Measuring neurogenesis via the granule cell layer volume of the dentate gyrus.

Main Results:

• Environmentally enriched (EE) mice exhibited significant forgetting compared to standard (SE) mice (reduced freezing time).
• Increased fractional anisotropy (FA) in white matter tracts (anterior commissure, cerebral peduncle, corpus callosum, cortical spinal tract, fimbria) was observed in EE mice.
• Higher FA in the corpus callosum and fimbria predicted reduced freezing, linking white matter changes to forgetting.
• Clemastine fumarate administration induced forgetting in male mice.
• Neurogenesis independently predicted forgetting.

Conclusions:

• Myelin-related plasticity in white matter tracts supporting contextual fear memory plays a role in enrichment-induced forgetting.
• Environmental enrichment can lead to forgetting through alterations in white matter structure and function.
• These findings reveal a novel mechanism of forgetting involving white matter plasticity.