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2015 ; 5
(ä): 14366
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Inhibitory luminopsins: genetically-encoded bioluminescent opsins for versatile,
scalable, and hardware-independent optogenetic inhibition
#MMPMID26399324
Tung JK
; Gutekunst CA
; Gross RE
Sci Rep
2015[Sep]; 5
(ä): 14366
PMID26399324
show ga
Optogenetic techniques provide an unprecedented ability to precisely manipulate
neural activity in the context of complex neural circuitry. Although the toolbox
of optogenetic probes continues to expand at a rapid pace with more efficient and
responsive reagents, hardware-based light delivery is still a major hurdle that
limits its practical use in vivo. We have bypassed the challenges of external
light delivery by directly coupling a bioluminescent light source (a genetically
encoded luciferase) to an inhibitory opsin, which we term an inhibitory
luminopsin (iLMO). iLMO was shown to suppress action potential firing and
synchronous bursting activity in vitro in response to both external light and
luciferase substrate. iLMO was further shown to suppress single-unit firing rate
and local field potentials in the hippocampus of anesthetized rats. Finally,
expression of iLMO was scaled up to multiple structures of the basal ganglia to
modulate rotational behavior of freely moving animals in a hardware-independent
fashion. This novel class of optogenetic probes demonstrates how non-invasive
inhibition of neural activity can be achieved, which adds to the versatility,
scalability, and practicality of optogenetic applications in freely behaving
animals.