Brain Star Award Winner Sasha McDowell

Sasha McDowell

Sasha McDowell | University of British Columbia

Scientific publication
McDowell, S. A. T., Stanley, M., & Gordon, M. D. (2022). A molecular mechanism for high salt taste in Drosophila. Current biology : CB, 32(14), 3070–3081.e5.

Understanding the mechanism for high salt taste in fruit flies

Salt is essential for many physiological processes, including neuronal transmission, muscle contraction, nutrient absorption and to maintain optimal electrolyte levels. However, too much salt can have ill effects. To ensure optimal salt consumption, both mammals and insects display a concentration dependent switch in feeding behaviour, where low levels of salt are attractive, but very high levels become feeding deterrents. To optimize salt intake, animals employ salt-dependent activation of multiple taste pathways. Generally, sodium (found in table salt) activates attractive taste cells, but attraction is overridden at high salt concentrations by non-selective activation of aversive taste cells. In fruit flies, high salt avoidance is driven by both “bitter” taste neurons and a class of “high salt” neurons. In this paper, Sasha McDowell, a PhD student at the University of British Columbia, shows in fruit flies that a specific receptor called IR7c is expressed in high salt neurons, where it functions with co-receptors IR76b and IR25a to detect high salt and is essential for salt taste. When the researcher added the IR7c receptor in sweet neurons, which normally express IR76b and IR25a, these neurons became responsive to non-sodium salts, indicating that IR7c is sufficient to convert a selective gustatory receptor neuron to a non-selective one. Furthermore, this transformed a salt that is normally aversive, potassium chloride, into an attractive taste.
Of the primary taste modalities in mammals, “high salt” (aversive responses to high salt concentrations) is the last without an identified receptor. Drosophila (fruit fly) has been extensively used as a model to probe the mechanisms of sensory detection in a simpler organism, yet we also did not have a clear understanding of high salt taste in flies, or any other animal. Early insights revealed that two broad co-receptors, IR25a and IR76b, are necessary for non-selective high salt taste in flies, but they are also critical for sodium-selective attractive salt taste as well as numerous other taste responses. Identifying IR7c as a salt-specific receptor subunit that works with IR25a and IR76b to form a functional high salt receptor sheds important light on the mechanisms of high salt neuron tuning, and how selectivity is achieved in receptor complexes. It may also reveal general principles of salt sensors that are relevant to high salt detection in mammals.

Finally, this study revealed that internal state (prior salt consumption) affects both attractive and aversive salt pathways, opening the door to understanding the mechanisms underlying this critical level of homeostatic regulation.

About Sasha McDowell

Sasha McDowell holds a Bachelor of Science in Biology with First-Class Honours from McGill University. Curious about neural circuits underlying behaviour, Sasha went on to pursue a PhD in Zoology at the University of British Columbia where she is now studying salt taste processing and feeding behaviour in Drosophila melanogaster under the supervision of Dr. Michael Gordon. Together with her supervisor, they conceived the project and experimental approaches. Sasha McDowell performed all of the experiments and analyses, and created a first draft of the manuscript, and conducted all revision experiments with guidance from her supervisor prior to final publication.

Source of funding:

This work was funded by the Canadian Institutes of Health Research (CIHR) operating grant FDN-148424.