UV to blue neuronal phototransduction mechanisms

NIH RePORTER · NIH · R35 · $520,499 · view on reporter.nih.gov ↗

Abstract

Many insects pose major health and economic hazards to humans as common disease vectors and agricultural pests. Almost all of our present understanding of insect phototransduction is based on opsin-based photoreception in eyes that mediate image forming vision. My lab has recently discovered two additional phototransduction mechanisms in Drosophila. Cryptochrome (CRY) and Rhodopsin 7 (Rh7) expressed in central brain neurons mediate rapid onset sustained electrophysiological responses in these neurons. CRY and Rh7 light signaling underlie a novel form of non-image forming vision that strongly modulates complex time-of-day dependent insect behavioral responses to light, including avoidance/attraction behavioral choice between light and shade and light evoked arousal. While CRY's mechanism of action is due to light evoked redox state changes of its flavin adenine dinucleotide (FAD) chromophore and Rh7's mechanism of action is through a G- protein signaling pathway, they physiologically interact and may form the basis of a true color vision system for non-image forming vision that discerns specific light spectra. We have extended our study of non-image forming vision to harmful nocturnal Anopheles gambiae and diurnal Aedes aegypti mosquitoes and find that CRY1s mediate very distinct time-of-day dependent species specific behavioral light responses in these mosquitp-o important disease vectors. Remarkably, nocturnal and diurnal mosquito CRY1s confer mosquito species specific behavioral effects when expressed in all CRY expressing cells in a cry-null Drosophila genetic background and nocturnal mosquito CRY1 is significantly more light sensitive than diurnal mosquito CRY1 measured by multiple behavioral and electrophysiological assays. We will determine the detailed mechanisms that confer species specific physiological and behavioral light responses for flies and mosquitoes and other insects using a highly sensitive electrophysiological assay that we have developed that will allow us to accurately measure redox state changes and biological outputs for light sensitive CRYs and functional interactions between CRYs and Rh7, in combination with behavioral analysis. Our custom designed instrumentation allows us to examine CRY spectrally driven redox state changes in vivo. Present insect control strategies rely heavily on highly toxic pesticides. A far more environmentally friendly alternative is to make use of light-based behavioral manipulation of insects in a species specific fashion to attract harmful insect species to traps or to repel them away from human habitation. The goal of our research to form a rational basis for designing innovative new LED devices for species-specific harmful insect control in the ongoing fight against vector-borne diseases.

Key facts

NIH application ID
10621560
Project number
2R35GM127102-06
Recipient
UNIVERSITY OF CALIFORNIA-IRVINE
Principal Investigator
Todd C Holmes
Activity code
R35
Funding institute
NIH
Fiscal year
2023
Award amount
$520,499
Award type
2
Project period
2018-04-01 → 2028-03-31