PUBLICATION

A family of photoswitchable NMDA receptors

Authors
Berlin, S., Szobota, S., Reiner, A., Carroll, E.C., Kienzler, M.A., Guyon, A., Xiao, T., Tauner, D., Isacoff, E.Y.
ID
ZDB-PUB-160302-5
Date
2016
Source
eLIFE   5: (Journal)
Registered Authors
Isacoff, Ehud, Xiao, Tong
Keywords
NMDA receptor, gluN2, liGluN, mouse, neuroscience, photoswitch, synapse, synaptic plasticity
MeSH Terms
  • Action Potentials
  • Animals
  • Hippocampus/physiology
  • Light*
  • Neurons/physiology
  • Receptors, N-Methyl-D-Aspartate/genetics
  • Receptors, N-Methyl-D-Aspartate/metabolism*
  • Receptors, N-Methyl-D-Aspartate/radiation effects*
  • Recombinant Proteins/genetics
  • Recombinant Proteins/metabolism
  • Zebrafish/embryology
PubMed
26929991 Full text @ Elife
Abstract
NMDA receptors, which regulate synaptic strength and are implicated in learning and memory, consist of several subtypes with distinct subunit compositions and functional properties. To enable spatiotemporally defined, rapid and reproducible manipulation of function of specific subtypes, we engineered a set of photoswitchable GluN subunits ('LiGluNs'). Photo-agonism of GluN2A or GluN2B elicits an excitatory drive to hippocampal neurons that can be shaped in time to mimic synaptic activation. Photo-agonism of GluN2A at single dendritic spines evokes spine-specific calcium elevation and expansion, the morphological correlate of LTP. Photo-antagonism of GluN2A alone, or in combination with photo-antagonism of GluN1a, reversibly blocks excitatory synaptic currents, prevents the induction of long-term potentiation and prevents spine expansion. In addition, photo-antagonism in vivo disrupts synaptic pruning of developing retino-tectal projections in larval zebrafish. By providing precise and rapidly reversible optical control of NMDA receptor subtypes, LiGluNs should help unravel the contribution of specific NMDA receptors to synaptic transmission, integration and plasticity.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes