Optical control of NMDA receptors with a diffusible photoswitch.

Abstract:

:N-methyl-D-aspartate receptors (NMDARs) play a central role in synaptic plasticity, learning and memory, and are implicated in various neuronal disorders. We synthesized a diffusible photochromic glutamate analogue, azobenzene-triazole-glutamate (ATG), which is specific for NMDARs and functions as a photoswitchable agonist. ATG is inactive in its dark-adapted trans-isoform, but can be converted into its active cis-isoform using one-photon (near UV) or two-photon (740 nm) excitation. Irradiation with violet light photo-inactivates ATG within milliseconds, allowing agonist removal on the timescale of NMDAR deactivation. ATG is compatible with Ca(2+) imaging and can be used to optically mimic synaptic coincidence detection protocols. Thus, ATG can be used like traditional caged glutamate compounds, but with the added advantages of NMDAR specificity, low antagonism of GABAR-mediated currents, and precise temporal control of agonist delivery.

journal_name

Nat Commun

journal_title

Nature communications

authors

Laprell L,Repak E,Franckevicius V,Hartrampf F,Terhag J,Hollmann M,Sumser M,Rebola N,DiGregorio DA,Trauner D

doi

10.1038/ncomms9076

subject

Has Abstract

pub_date

2015-08-27 00:00:00

pages

8076

issn

2041-1723

pii

ncomms9076

journal_volume

6

pub_type

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