Optogenetics

Optogenetic

The optogenetic is a powerful tool that allows to control the neuronal activity in a selective manner. This is made possible with the use of lasers calibrated to specific wavelengths, providing a highly accurate spatio-temporal precision. Nociceptors, which are in fact afferent neurons, could therefore be modulated on demand using this technology. This would allow to study pain-related underlying mechanisms and behaviors linked to the differential expression of genes investigated for their potential role in chronic pain.  

This project lead the way to the acquisition of transgenic constructs in order to investigate the specific function of dorsal root ganglia (DRG) neurons and those of the trigeminal nerve (TG). Several material transfer agreements (MTA) were signed to allow the importation of different Cre lines targetting the somatosensory system. Using binary genetic algorithms, these lines allowed the development and breeding of transgenic mice optogeneticaly inducible. These mice express excitatory (ChR2) and inhibitory (NpHR, Arch) opsins in DRG and TG neuronal subpopulations as well as in sympathetic neurons.

The following Cre lines are available to members of the QPRN, as well as the opsin donors and their lineage: 

CRE LINES (DRIVERS) AND TARGETS

Nav1.8-Cre

Nociceptors, Mechanoreceptors

(John Wood, UCL)

TRPV1-Cre

Peptidergic nociceptors

( David Julius, UCSF)

MrgprD-CreER

Non-peptidergic nociceptors

(Wenwin Luo,  U. Penn)

MrgprA3-Cre

Itch neurons/nociceptors

(Xinzhong Dong, Johns Hopkins)

TH-Cre

C-low threshold mechanoreceptors

(Ted Dawson, Johns Hopkins)

DBH-CreER

Sympathetic neurons

(Hermann Rohrer, MPI Frankfurt)


OPSIN LINES

ROSA26-CAG-LSL-ChR2(H134R)-EYFP

(Hongkui Zeng, Allen Brain Institute)

ROSA26-CAG-LSL-NpHR3-EGFP

(Hongkui Zeng, Allen Brain Institute)

ROSA26-CAG-LSL-Arch3.0-EGFP

(Ed Boyden, MIT)

ROSA26-CAG-LSL-ArchT-EGFP

(Ed Boyden, MIT)

 

TRANSGENIC CURRENTLY AVAILABLE FOR IN VIVO OPTOGGENETICS

Nav1.8/ChR2

Nav1.8/NpHR3

Nav1.8/Arch3.0

Nav1.8/ArchT

Nav1.8/ChR2+ArchT

TRPV1/ChR2

MrgprD/ChR2 (inducible)

MrgprA3/ChR2

TH/ChR2

DBH/ChR2 (inducible)