Title | Optogenetic inhibition of synaptic release with chromophore-assisted light inactivation (CALI). |
Publication Type | Journal Article |
Year of Publication | 2013 |
Auteurs | Lin, JY, Sann, SB, Zhou, K, Nabavi, S, Proulx, CD, Malinow, R, Jin, Y, Tsien, RY |
Journal | Neuron |
Volume | 79 |
Issue | 2 |
Pagination | 241-53 |
Date Published | 2013 Jul 24 |
ISSN | 1097-4199 |
Keywords | Animals, Animals, Newborn, Caenorhabditis elegans, Cells, Cultured, Chromophore-Assisted Light Inactivation, Hippocampus, Neural Inhibition, Optogenetics, Organ Culture Techniques, Rats, Rats, Sprague-Dawley, Synapses, Synaptic Transmission |
Abstract | Optogenetic techniques provide effective ways of manipulating the functions of selected neurons with light. In the current study, we engineered an optogenetic technique that directly inhibits neurotransmitter release. We used a genetically encoded singlet oxygen generator, miniSOG, to conduct chromophore assisted light inactivation (CALI) of synaptic proteins. Fusions of miniSOG to VAMP2 and synaptophysin enabled disruption of presynaptic vesicular release upon illumination with blue light. In cultured neurons and hippocampal organotypic slices, synaptic release was reduced up to 100%. Such inhibition lasted >1 hr and had minimal effects on membrane electrical properties. When miniSOG-VAMP2 was expressed panneuronally in Caenorhabditis elegans, movement of the worms was reduced after illumination, and paralysis was often observed. The movement of the worms recovered overnight. We name this technique Inhibition of Synapses with CALI (InSynC). InSynC is a powerful way to silence genetically specified synapses with light in a spatially and temporally precise manner. |
DOI | 10.1016/j.neuron.2013.05.022 |
Alternate Journal | Neuron |
PubMed ID | 23889931 |
PubMed Central ID | PMC3804158 |
Grant List | R01 NS035546 / NS / NINDS NIH HHS / United States F32 NS067891 / NS / NINDS NIH HHS / United States MH091119 / MH / NIMH NIH HHS / United States NS035546 / NS / NINDS NIH HHS / United States / / Howard Hughes Medical Institute / United States R01 NS027177 / NS / NINDS NIH HHS / United States NS027177 / NS / NINDS NIH HHS / United States NS067891 / NS / NINDS NIH HHS / United States R37 NS027177 / NS / NINDS NIH HHS / United States R01 MH091119 / MH / NIMH NIH HHS / United States R01 MH049159 / MH / NIMH NIH HHS / United States |