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Increased axonal bouton dynamics in the aging mouse cortex.

Federico W Grillo1, Sen Song, Leonor M Teles-Grilo Ruivo

  • 1Medical Research Council Clinical Science Centre, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom.

Proceedings of the National Academy of Sciences of the United States of America
|April 2, 2013
PubMed
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Aging brains exhibit increased axonal bouton dynamics, not synapse loss. This heightened structural turnover, especially in large boutons, may explain age-related memory decline by reducing synaptic stability.

Area of Science:

  • Neuroscience
  • Aging Research
  • Synaptic Plasticity

Background:

  • Aging is a significant risk factor for neurological diseases and cognitive decline.
  • Previous research suggests aging reduces synapse number and plasticity, but lacked in vivo evidence.
  • The dynamic nature of synaptic structures in the intact aged brain remains largely unknown.

Purpose of the Study:

  • To investigate whether neuronal structures remain dynamic in the intact aged brain.
  • To determine if specific synaptic deficits arise during aging.
  • To examine axonal bouton dynamics in vivo in aged mice.

Main Methods:

  • Utilized in vivo two-photon imaging in aged mice.
  • Developed a novel analysis method to track axonal bouton size and location.

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  • Quantified bouton formation, elimination, and destabilization rates.

    • Main Results:

    • Aged cortex shows increased, circuit-specific rates of axonal bouton formation, elimination, and destabilization.
    • Large boutons in aged mice exhibit 10-fold higher destabilization and 20-fold higher turnover than in young adults.
    • Persistent boutons in aged brains show larger size fluctuations, impacting memory encoding.

    Conclusions:

    • Aging increases axonal bouton dynamics in the cortex, particularly destabilization and turnover of strong synapses.
    • Age-related cognitive decline may stem from decreased synaptic tenacity rather than an inability to form new synapses.
    • Increased synaptic structural dynamics in cortical circuits could be a key mechanism underlying age-related cognitive impairment.