Flashy Science: Controlling Neural Function with Light

Targeting and Readout Strategies for Fast Optical Neural ControlIn VitroandIn Vivo

“…To address different aspects of these technical constraints, genetically targetable neural modulation tools have been developed by a number of groups (Zemelman et al, 2002;Banghart et al, 2004;Karpova et al, 2005;Lima and Miesenbock, 2005;Thompson et al, 2005;Chambers et al, 2006;Tan et al, 2006;Gorostiza et al, 2007;Lerchner et al, 2007;. One approach recently brought to neurobiology, combining both high speed and genetic targeting, is based on a family of fast light-responsive microbial opsins including halorhodopsins (e.g., NpHR) and channelrhodopsins (e.g., ChR2) (for review, see Zhang et al, 2007b).…”

Laser photolysis of caged compounds at 405nm: Photochemical advantages, localisation, phototoxicity and methods for calibration

“…Recent improvements in the chemistry of caged neurotransmitters, particularly the development of the hydrolytically stable, fast (sub-s) nitroindoline-caged amino acids (Papageorgiou et al, 1999;Morrison et al, 2002), permits the use of photolysis with near-UV excitation (reviewed in Thompson et al, 2005) or pulsed IR with the two-photon effect (Matsuzaki et al, 2001;Smith et al, 2003) to mimic synaptic activation. The precision and speed of laser scanning microscopes (Gasparini and Magee, 2006;Losonczy and Magee, 2006) or of holographic techniques (Lutz et al, 2008) can be used to localise release.…”

Exclusive photorelease of signalling lipids at the plasma membrane

“…Successful approaches for manipulating the cellular levels of small signalling molecules within a millisecond to second timeframe usually involve either chemical 5 6 or optogenetic 7 8 protein modulation systems for generating second messengers in situ or photoactivatable (caged) small molecules, which release the active species upon illumination 9 10 . Prominent examples of caged small molecules that have been employed in cell biology include lipids, nucleotides and neurotransmitters 11 12 13 14 15 16 17 . One major advantage of utilizing caged compounds is the possibility of stepwise concentration increases of signalling molecules to a fixed level from which they are subsequently metabolized.…”