A family of photoswitchable NMDA receptors

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 engineere...

Full description

Saved in:
Bibliographic Details
Published in:eLife 2016-03, Vol.5
Main Authors: Berlin, Shai, Szobota, Stephanie, Reiner, Andreas, Carroll, Elizabeth C, Kienzler, Michael A, Guyon, Alice, Xiao, Tong, Trauner, Dirk, Isacoff, Ehud Y
Format: Article
Language:English
Subjects:
Action Potentials
Animals
BASIC BIOLOGICAL SCIENCES
Calcium
Cell receptors
Dendritic spines
GluN2
Glutamic acid receptors (ionotropic)
Hippocampus
Hippocampus - physiology
Laboratory animals
Learning
Life Sciences & Biomedicine - Other Topics
Ligands
Light
LiGluN
Long-term potentiation
Memory
Methyl aspartate
N-Methyl-D-aspartic acid receptors
Neurons - physiology
Neuroscience
Neurosciences
NMDA receptor
photoswitch
Physiological aspects
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
Rodents
synapse
Synaptic plasticity
Synaptic strength
Synaptic transmission
Variance analysis
Zebrafish - embryology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.12040