Institution: Ludwig-Maximilians-Universität München
Department: Department of Chemistry
Z03 until 12/2013
About project Z03 (completed 12/2013)
Project title: Functional manipulation of glutamate receptors for circuitry mapping
Summary: As originally proposed (Aim 1), we have succeeded in developing a light-gated glutamate receptor with a redshifted action spectrum (Fig. 1). The application of this system in the restoration of vision is currently under investigation in collaboration with Prof. Ehud Isacoff (UC Berkeley). Similarly, we have succeeded in rendering an NMDA receptor light-sensitive, using a photoswitched tethered glutamate, MAG, which we have previously employed in the kainate-receptor based LiGluR system (Aim 2).
In addition, we have developed a photoswitchable small molecule, termed Azobenze Triazole Glutamate (ATG), which can reversibly activate NMDARs in a light- dependent fashion. ATG is highly selective for NMDA receptors, is inactive in its dark-adaptive trans-form, and converts into its active cis-form upon irradiation with 370 nm. Thus, it is not excitotoxic in the absence of light, but becomes an effective agonist when irradiated. Following photochemical trans-cis isomerisation, ATG converts back slowly (within seconds) to its inactive state, but can be actively switched off with blue light (420 nm) within a few milliseconds.