Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786437/ https://www.ncbi.nlm.nih.gov/pubmed/26929991 http://dx.doi.org/10.7554/eLife.12040 |
_version_ | 1782420552465514496 |
---|---|
author | Berlin, Shai Szobota, Stephanie Reiner, Andreas Carroll, Elizabeth C Kienzler, Michael A Guyon, Alice Xiao, Tong Trauner, Dirk Isacoff, Ehud Y |
author_facet | Berlin, Shai Szobota, Stephanie Reiner, Andreas Carroll, Elizabeth C Kienzler, Michael A Guyon, Alice Xiao, Tong Trauner, Dirk Isacoff, Ehud Y |
author_sort | Berlin, Shai |
collection | PubMed |
description | 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. DOI: http://dx.doi.org/10.7554/eLife.12040.001 |
format | Online Article Text |
id | pubmed-4786437 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-47864372016-03-17 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 eLife Neuroscience 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. DOI: http://dx.doi.org/10.7554/eLife.12040.001 eLife Sciences Publications, Ltd 2016-03-01 /pmc/articles/PMC4786437/ /pubmed/26929991 http://dx.doi.org/10.7554/eLife.12040 Text en © 2016, Berlin et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience 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 |
title | A family of photoswitchable NMDA receptors |
title_full | A family of photoswitchable NMDA receptors |
title_fullStr | A family of photoswitchable NMDA receptors |
title_full_unstemmed | A family of photoswitchable NMDA receptors |
title_short | A family of photoswitchable NMDA receptors |
title_sort | family of photoswitchable nmda receptors |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786437/ https://www.ncbi.nlm.nih.gov/pubmed/26929991 http://dx.doi.org/10.7554/eLife.12040 |
work_keys_str_mv | AT berlinshai afamilyofphotoswitchablenmdareceptors AT szobotastephanie afamilyofphotoswitchablenmdareceptors AT reinerandreas afamilyofphotoswitchablenmdareceptors AT carrollelizabethc afamilyofphotoswitchablenmdareceptors AT kienzlermichaela afamilyofphotoswitchablenmdareceptors AT guyonalice afamilyofphotoswitchablenmdareceptors AT xiaotong afamilyofphotoswitchablenmdareceptors AT traunerdirk afamilyofphotoswitchablenmdareceptors AT isacoffehudy afamilyofphotoswitchablenmdareceptors AT berlinshai familyofphotoswitchablenmdareceptors AT szobotastephanie familyofphotoswitchablenmdareceptors AT reinerandreas familyofphotoswitchablenmdareceptors AT carrollelizabethc familyofphotoswitchablenmdareceptors AT kienzlermichaela familyofphotoswitchablenmdareceptors AT guyonalice familyofphotoswitchablenmdareceptors AT xiaotong familyofphotoswitchablenmdareceptors AT traunerdirk familyofphotoswitchablenmdareceptors AT isacoffehudy familyofphotoswitchablenmdareceptors |