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Updated: Jun 20, 2025

Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
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Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology

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Myelin dystrophy impairs signal transmission and working memory in a multiscale model of the aging prefrontal cortex

Sara Ibañez1,2,3, Nilapratim Sengupta1,4, Jennifer I Luebke1

  • 1Department of Anatomy & Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, United States.

Elife
|July 19, 2024
PubMed

Insights

Aging impairs working memory by altering myelin in the brain. Computational models show that myelin damage, even with some repair, significantly reduces cognitive function, highlighting the impact of myelin changes on brain health.

Area of Science:

  • Neuroscience
  • Computational Biology
  • Cognitive Science

Background:

  • Normal aging causes myelin alterations in the rhesus monkey dorsolateral prefrontal cortex (dlPFC).
  • These myelin changes correlate with cognitive impairment.
  • Partial remyelination may compensate for myelin degradation, but this has not been systematically modeled.

Purpose of the Study:

  • To computationally investigate how age-related myelin changes affect spatial working memory.
  • To model the combined effects of demyelination and remyelination on neuronal function and network activity.

Main Methods:

  • Developed a multicompartment pyramidal neuron model based on monkey dlPFC data, including detailed axonal myelination.
  • Quantified changes in conduction velocity (CV) and action potential (AP) failures due to demyelination and remyelination.
  • Integrated single-neuron findings into a spiking neural network model of working memory.

Main Results:

  • Complete remyelination largely restored axonal transmission and network function.
  • Biologically plausible levels of myelin damage, without full compensation, were predicted to cause significant working memory impairment in aging.
  • Model results link ultrastructural changes to behavioral outcomes in aging.

Conclusions:

  • Computational models predict that uncompensated myelin damage significantly contributes to age-related working memory deficits.
  • The findings have implications for understanding demyelinating diseases like multiple sclerosis and schizophrenia.
  • This study integrates empirical data across multiple biological scales to explain aging-related cognitive decline.
Keywords:
agingbump attractorcomputational biologymulticompartment modelmyelin dystrophyneurosciencenonerhesus monkeysystems biologyworking memory

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