Optogenetic inhibition of synaptic release with chromophore-assisted light inactivation (CALI).

TitleOptogenetic inhibition of synaptic release with chromophore-assisted light inactivation (CALI).
Publication TypeJournal Article
Year of Publication2013
AuteursLin, JY, Sann, SB, Zhou, K, Nabavi, S, Proulx, CD, Malinow, R, Jin, Y, Tsien, RY
JournalNeuron
Volume79
Issue2
Pagination241-53
Date Published2013 Jul 24
ISSN1097-4199
KeywordsAnimals, 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.

DOI10.1016/j.neuron.2013.05.022
Alternate JournalNeuron
PubMed ID23889931
PubMed Central IDPMC3804158
Grant ListR01 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