Neural activity regulates synaptic properties and dendritic structure in vivo through calcineurin/NFAT signaling.
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.
Schwartz
Neil
N
Montreal Neurological Institute, McGill University, Montréal, QC H3A 2B4, Canada.
Schohl
Anne
A
Ruthazer
Edward S
ES
D000818:Animals; D001921:Brain / Q000166:cytology; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D018274:Electroporation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D021621:Imaging, Three-Dimensional / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation / Q000379:methods; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D016559:Tacrolimus / Q000494:pharmacology; D013997:Time Factors; D014981:Xenopus
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D050778:NFATC Transcription Factors; D018091:Receptors, AMPA; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D019703:Calcineurin; D016559:Tacrolimus