This video features a talk by professor of biology Paul Garrity and postdoctoral fellow Gonzalo Budelli about their January 14, 2019, paper in Neuron, entitled, “Ionotropic Receptors Specify the Morphogenesis of Phasic Sensors Controlling Rapid Thermal Preference in Drosophila.”
We hear Paul Garrity speak: "I’m Paul Garrity, a professor in the Department of Biology at Brandeis University, in Waltham MA, near Boston."
We hear Gonzalo Budelli speak: "And I’m Gonzalo Budelli, a post-doc in the Garrity lab. In our lab, we are interested in how animals sense and respond to the world around them."
Garrity: In our paper, we use the fruit fly Drosophila melanogaster to probe how sensory neurons encode temperature. Previous work has found that flies rely on a small number of temperature-sensing neurons located in the arista, a tiny structure near the tip of the antenna. These neurons were known to be very responsive to temperature, but precisely how the encoded the temperature information, whether, they responded to absolute temperature (like a thermometer), or instead sensed only changes in temperature, was unknown.
Budelli: To test this, I established a preparation that allowed me to examine the spiking of these neurons. By focusing on the Cooling-activated neurons, I discovered that rather than sensing absolute temperature, these neurons responded to temperature changes – what I mean by this is that the neurons were activated by cooling and inhibited .
Garrity: We next examined these neurons at the molecular level. We found they expressed three members of a family of invertebrate-specific sensory receptors called the IRs. These IRs turned out to be absolutely required for the neurons to sense temperature.
We got a big surprise when Cristina and Dani examined the structure of these mutant neurons using electron microscopy. The sensory endings of these neurons normally form elaborate structures in which the plasma membrane folds in itself, forming a network linked by extracellular bridges called BOSS elements.
In the IR mutants, both the membrane folds and the BOSS elements are gone. Furthermore, ectopic IR expression caused the adjacent cell to form BOSSes with the Cooling Cell and even become a cooling-sensitive cell itself. This suggests that these structures are critical for temperature sensing. Furthermore, while IR family members have been viewed solely as stimulus-responsive ion channels, our data show they can also serve as key regulators of morphogenesis.
This work suggests that thermotransduction by these neurons is tightly linked to their morphological specialization. This is a phenomenon usually associated with mechanosensors rather than thermosensors, and it suggests potential similarities between what are conventionally considered separate sensory modalities.
Budell: Finally, my data showed that the Cooling Cells showed the same responses to temperature changes no matter what the absolute temperature was. This suggested that even though these neurons are activated by cooling, at the behavioral level they might be important for both warm and cool avoidance. Indeed, mutants with inactive Cooling Cells were unable to avoid temperatures that were too warm as well as temperatures that were too cold.
Our study raises many questions: What proteins are required to form BOSSes and how do these structures affect neuronal function? How do the Cooling Cells actually sense cooling? And while phasic sensors like the Cooling Cells are powerful tools for the animal, they are unlikely to act alone: how does the fly know whether it is too warm or too cold?
Garrity: As analogous systems operate in disease-transmitting mosquitoes and even in humans, we hope that answering these questions will not only be fascinating, but provide useful insights of general interest – for example, helping provide ways to combat the spread of mosquito-borne diseases.
Gonzalo and I had a team of talented collaborators for this work, which include members of our lab here at Brandeis and in labs at the University of Texas Southwestern Medical School, the University of Lausanne, Harvard University and the University of Miami. We also acknowledge our funders for their support.