A family of photoswitchable NMDA receptors

Shai Berlin, Stephanie Szobota, Andreas Reiner, Elizabeth C. Carroll, Michael A. Kienzler, Alice Guyon, Tong Xiao, Dirk Trauner, Ehud Y. Isacoff

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere12040
JournaleLife
Volume5
Issue numberMARCH2016
DOIs
StatePublished - Mar 1 2016

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N-Methyl-D-Aspartate Receptors
Neuronal Plasticity
Spine
Dendritic Spines
Long-Term Potentiation
Zebrafish
Synaptic Transmission
Neurons
Plasticity
Chemical activation
Learning
Calcium
Data storage equipment
Chemical analysis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Berlin, S., Szobota, S., Reiner, A., Carroll, E. C., Kienzler, M. A., Guyon, A., ... Isacoff, E. Y. (2016). A family of photoswitchable NMDA receptors. eLife, 5(MARCH2016), [e12040]. https://doi.org/10.7554/eLife.12040

A family of photoswitchable NMDA receptors. / Berlin, Shai; Szobota, Stephanie; Reiner, Andreas; Carroll, Elizabeth C.; Kienzler, Michael A.; Guyon, Alice; Xiao, Tong; Trauner, Dirk; Isacoff, Ehud Y.

In: eLife, Vol. 5, No. MARCH2016, e12040, 01.03.2016.

Research output: Contribution to journalArticle

Berlin, S, Szobota, S, Reiner, A, Carroll, EC, Kienzler, MA, Guyon, A, Xiao, T, Trauner, D & Isacoff, EY 2016, 'A family of photoswitchable NMDA receptors', eLife, vol. 5, no. MARCH2016, e12040. https://doi.org/10.7554/eLife.12040
Berlin S, Szobota S, Reiner A, Carroll EC, Kienzler MA, Guyon A et al. A family of photoswitchable NMDA receptors. eLife. 2016 Mar 1;5(MARCH2016). e12040. https://doi.org/10.7554/eLife.12040
Berlin, Shai ; Szobota, Stephanie ; Reiner, Andreas ; Carroll, Elizabeth C. ; Kienzler, Michael A. ; Guyon, Alice ; Xiao, Tong ; Trauner, Dirk ; Isacoff, Ehud Y. / A family of photoswitchable NMDA receptors. In: eLife. 2016 ; Vol. 5, No. MARCH2016.
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