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A family of photoswitchable NMDA receptors

Journal Article · · eLife
DOI:https://doi.org/10.7554/elife.12040· OSTI ID:1628842
 [1];  [2];  [2];  [2];  [2];  [3];  [4];  [5];  [6]
  1. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; DOE/OSTI
  2. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology
  3. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Université de Nice Sophia Antipolis, Nice (France). Institut de Pharmacologie Moléculaire et Cellulaire,
  4. Univ. of California, Berkeley, CA (United States). Dept. of Chemistry
  5. Univ. of Munich (Germany). Center of Integrated Protein Science. Dept. of Chemistry
  6. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Bioscience Division

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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1628842
Journal Information:
eLife, Journal Name: eLife Vol. 5; ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.Copyright Statement
Country of Publication:
United States
Language:
English

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Cited By (10)

Astroglial Glutamate Signaling and Uptake in the Hippocampus journal January 2018
Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos journal January 2020
In silico hippocampal modeling for multi-target pharmacotherapy in schizophrenia journal September 2020
Optical control of neuronal ion channels and receptors journal July 2019
Holographic two-photon activation for synthetic optogenetics journal February 2019
Azobenzene photocontrol of peptides and proteins journal January 2016
Photochromism into nanosystems: towards lighting up the future nanoworld journal January 2018
Light-responsive bicyclic peptides journal January 2018
Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos text January 2020
Optogenetic control of excitatory post-synaptic differentiation through neuroligin-1 tyrosine phosphorylation journal April 2020

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