Optical control of NMDA receptors with a diffusible photoswitch.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26311290.
- Also identified by DOI 10.1038/ncomms9076 and PMC identifier 4560805.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- CA1 Region, Hippocampal
- Cerebral Cortex
- Glutamic Acid
- Light
- Pyramidal Cells
- Receptors, N-Methyl-D-Aspartate