Neural activity regulates synaptic properties and dendritic structure in vivo through calcineurin/NFAT signaling

Neuron. 2009 Jun 11;62(5):655-69. doi: 10.1016/j.neuron.2009.05.007.

Abstract

The calcium-regulated protein phosphatase Calcineurin (CaN) participates in synaptic plasticity and the regulation of transcription factors, including Nuclear Factor of Activated T cells (NFAT). To understand how CaN contributes to neuronal circuit development, whole-cell mEPSC recordings and multiphoton imaging were performed in the visual system of living Xenopus laevis tadpoles electroporated to express either a CaN phosphatase inhibitor or N-VIVIT, a nuclear localization sequence-tagged VIVIT peptide that blocks the binding of CaN to select substrates including NFAT. Both strategies increased mEPSC frequency and dendritic arbor complexity in tectal neurons over 3 days. Expression of either of two constitutively active Xenopus NFATs (CA-NFATs) restored normal synaptic properties in neurons expressing N-VIVIT. However, the morphological phenotype was only rescued by a CA-NFAT bearing an intact regulatory domain, implying that transcriptional control of morphological and electrophysiological properties of neurons is mediated by distinct NFAT interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Calcineurin / genetics
  • Calcineurin / metabolism*
  • Calcineurin Inhibitors
  • Dendrites / drug effects
  • Dendrites / physiology*
  • Electroporation / methods
  • Excitatory Postsynaptic Potentials / physiology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Imaging, Three-Dimensional / methods
  • Immunosuppressive Agents / pharmacology
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism*
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Photic Stimulation / methods
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Synapses / drug effects
  • Synapses / physiology*
  • Tacrolimus / pharmacology
  • Time Factors
  • Xenopus

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • NFATC Transcription Factors
  • Receptors, AMPA
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Calcineurin
  • Tacrolimus