Cosyne 2008 Workshops
March 3-4, 2008
Snow Bird, Utah
Speaker Name
Ehud Isacoff
Talk Title
Engineered light-gated excitatory receptors for analysis of the neural basis of behavior
Talk Abstract
The ability to stimulate select neurons is essential for investigating their role in circuits and behavior. We have synthesized a family of tethered glutamate photoswitches that covalently bind to glutamate receptors and modulate their activity in response to millisecond long pulses of light. Key photophysical and chemical properties of the photoswitches will be examined, including: a) “Photolithography” to constrain switch attachment spatially; b) Analog control of photocurrent magnitude; c) Bi-stable photoswitching that enables sustained activation in the dark to minimize photodamage and interference with behavioral assays; d) Agonist and antagonist switches; e) Altered receptors that are light-gated but minimally sensitive to native transmitter; g) Different attachment sites that flip the wavelength dependence of activation, yielding a pull-push control over activation; h) New protein targets for photoswitch control. Experiments will be described that employ these engineered light-gated channels to manipulate neural circuits in behaving zebrafish.
