دورية
Engineering a Light-Regulated GABAAReceptor for Optical Control of Neural Inhibition
العنوان: | Engineering a Light-Regulated GABAAReceptor for Optical Control of Neural Inhibition |
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المؤلفون: | Lin, Wan-Chen, Davenport, Christopher M., Mourot, Alexandre, Vytla, Devaiah, Smith, Caleb M., Medeiros, Kathryne A., Chambers, James J., Kramer, Richard H. |
المصدر: | ACS Chemical Biology; July 2014, Vol. 9 Issue: 7 p1414-1419, 6p |
مستخلص: | Optogenetics has become an emerging technique for neuroscience investigations owing to the great spatiotemporal precision and the target selectivity it provides. Here we extend the optogenetic strategy to GABAAreceptors (GABAARs), the major mediators of inhibitory neurotransmission in the brain. We generated a light-regulated GABAAreceptor (LiGABAR) by conjugating a photoswitchable tethered ligand (PTL) onto a mutant receptor containing the cysteine-substituted α1-subunit. The installed PTL can be advanced to or retracted from the GABA-binding pocket with 500 and 380 nm light, respectively, resulting in photoswitchable receptor antagonism. In hippocampal neurons, this LiGABAR enabled a robust photoregulation of inhibitory postsynaptic currents. Moreover, it allowed reversible photocontrol over neuron excitation in response to presynaptic stimulation. LiGABAR thus provides a powerful means for functional and mechanistic investigations of GABAAR-mediated neural inhibition. |
قاعدة البيانات: | Supplemental Index |
تدمد: | 15548929 15548937 |
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DOI: | 10.1021/cb500167u |