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Related Experiment Videos

Signaling mechanisms underlying reversible, activity-dependent dendrite formation.

Andrew R Vaillant1, Patrizia Zanassi, Gregory S Walsh

  • 1Center for Neuronal Survival, Brain Tumor Research Center, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4.

Neuron
|June 28, 2002
PubMed
Summary

Neuronal activity and nerve growth factor (NGF) promote reversible dendrite growth in sympathetic neurons by stabilizing microtubules. Specific signaling pathways must be inhibited simultaneously for dendrite retraction.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Developmental Biology

Background:

  • Neuronal activity and neurotrophins are critical for dendritic arbor development and plasticity.
  • Dendritic morphology is dynamic and influenced by cellular signaling pathways.

Purpose of the Study:

  • To investigate the role of neuronal activity in regulating dendritic arbor formation and stability.
  • To elucidate the intracellular signaling mechanisms underlying activity-dependent dendrite plasticity.

Main Methods:

  • Sympathetic neurons were stimulated using electrical stimulation, KCl depolarization, and cholinergic receptor activation.
  • The effects of nerve growth factor (NGF) on dendrite formation were assessed.
  • Microtubule-associated protein 2 (MAP2) association with microtubules and microtubule stability were analyzed.

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  • Inhibitors for CaMKII and the MEK-ERK pathway were used to probe signaling mechanisms.

    • Main Results:

    • Neuronal activity promotes reversible dendrite formation, an effect enhanced by NGF.
    • Activity-dependent dendrite formation correlates with increased MAP2 association with microtubules and enhanced microtubule stability.
    • Inhibition of CaMKII or MEK-ERK pathways individually reduced dendrite formation.
    • Simultaneous inhibition of both CaMKII and MEK-ERK pathways was necessary for dendrite retraction.

    Conclusions:

    • Neuronal activity regulates dendritic morphology via CaMKII and MEK-ERK signaling pathways.
    • These pathways modulate MAP2 interactions with microtubules, controlling reversible dendrite stability.
    • Activity and neurotrophins converge intracellularly to dynamically regulate dendritic structure.