RRC ID 58152
Author Williams RH, Tsunematsu T, Thomas AM, Bogyo K, Yamanaka A, Kilduff TS.
Title Transgenic Archaerhodopsin-3 Expression in Hypocretin/Orexin Neurons Engenders Cellular Dysfunction and Features of Type 2 Narcolepsy.
Journal J. Neurosci.
Abstract Optogenetics has become an invaluable tool for functional dissection of neural circuitry. While opsin expression is often achieved by viral injection, stably integrated transgenes offer some practical advantages. Here, we demonstrate successful transgenic expression of an inhibitory opsin in hypocretin/orexin neurons, which are thought to promote or maintain wakefulness. Both brief and prolonged illumination resulted in inhibition of these neurons and induced sleep. However, even in the absence of illumination, these cells exhibited altered electrical characteristics, particularly when transgene expression was high. These aberrant properties affected metabolism and sleep, resulting in a phenotype reminiscent of the narcolepsy Type 2, a sleep disorder for which no good animal model currently exists.
Volume 39(47)
Pages 9435-9452
Published 2019-11-20
DOI 10.1523/JNEUROSCI.0311-19.2019
PII JNEUROSCI.0311-19.2019
PMID 31628177
PMC PMC6867809
Mice B6D2-Tg(hOX-Arch/EGFP)1Ahky(RBRC05845)