Mechanisms of Excitation and Adaptation in Limulus Photoreceptors

Brandeis University, Waltham MA

Investigators

Abstract

The horseshoe crab found on the eastern seaboard of the United States has been a model organism for the study of vision for more than 50 years. Since the seminal work of Hartline, for which he got the Nobel Prize in Medicine, it has been clear that the eyes of this organism are particularly well suited for understand how the eye works. The proposed work has the aim of understanding how the light-sensitive neurons (photoreceptors) in these animals turn the light signal into an electrical response (excitation) that can be communicated to the brain. The overall process of excitation in these animals is still not understood, but it is clear that a long sequence of reactions is involved. A great deal of research by many investigators has led to a clear picture of the earliest steps and a strong beginning has been made towards an understanding of the last step, the actual generation of the electrical signal. The middle steps remain unclear. This grant will fund research to test whether the missing step is activation of the enzyme guanylate cyclase. A second goal is to understand how these photoreceptors rapidly compensate when background illumination changes, much as one would experience when going out into bright sunlight from a dim room. This process is termed light-adaptation. Although this process is known to be initiated by the release of calcium ions from stores inside the cell, it is not known what happens next. This grant will fund research to test whether any of several protein kinases, a class of enzymes that modify other enzymes, act to cause light adaptation. There has been increasing interest in understanding the answers to these questions because invertebrate phototransduction genes can be used to make vertebrate neurons sensitive to light. This result may be developed into a treatment for blindness or to probe brain function.