June 14, 2013

Neuron Tug-Of-War Determines How Flies Respond To Salt

April Flowers for - Your Universe Online

It´s a natural instinct to want to swat a fruit fly in your kitchen, but a group of researchers led by UC Santa Barbara´s Department of Molecular, Cellular, and Developmental Biology (MCDB) and the Neuroscience Research Institute (NRI) say don´t. According to their new study, that fly could have a major impact on our progress in deciphering sensory biology and animal behavior. And that might someday provide a better understanding of the human brain.

Craig Montell, Duggan Professor of MCDB and Neuroscience, led the team that has been studying the mechanisms underlying salt taste coding of Drosophila melanogaster (fruit flies). The team´s findings, reported in the journal Science, are rather remarkable.

The study explains the fundamental question of how an animal chooses low salt over high salt. In addition, it unravels the mechanism for how gustatory receptor neurons (GRNs) are activated by salt, an essential nutrient for all animals, including humans.

"The body needs sodium for crucial tasks like putting our muscles into action and letting brain cells communicate with each other, but too much sodium will cause heart problems and other health concerns," explains Yali Zhang, PhD, from Johns Hopkins University School of Medicine.

Scientists have long known that animals are attracted to low-salt foods over high-salt foods. What has remained a mystery, however, is how low-salt and high-salt taste perceptions are differentially encoded in GRNs, and how they induce distinct behavioral responses. The findings from this new study solve the mystery.

The team took a close up look of the fly equivalent of a tongue: its long, curly proboscis. To do this, they zoomed in on the proboscis' so-called sensilla, which are hair-like structures that serve as the fly's taste buds. By loading an electrode with a mixture of water and different concentrations of salt, and touching it to each type of sensilla, Zhang tested which concentrations of salt caused what behavior, using the same electrode to detect the electrical signals fired by the sensilla in response to the salt.

They found fruit flies use two distinct types of salt GRNs to react to different concentrations of salt. The first type is activated maximally by low salt and induces attractive feeding behavior. The second type is activated primarily by high-salt and induces aversive feeding behavior. These two types of neurons compete with each other, the scientists found, to regulate the animal´s behavioral outputs. The relative strength of salt-attractive GRNs and salt-aversive GRNs determines the net outcome of the salt behavioral response. The identification of the underlying salt taste coding mechanism represents a conceptual breakthrough for the team.

"Ultimately, what we want to understand is behavior, which depends on sensory input and an animal's genetic makeup," said Montell. "Once you have this information and the neuronal wiring, you can predict the behavior of a population of animals. By focusing on behavior and perception in fruit flies, it may be just a few years before we have a rather impressive understanding about how sensory perceptions translate into behavior. That's why there's so much attention paid to model organisms like flies."

The study findings also reveal that a member of the newly discovered ionotropic receptor (IR) family, IR76b, is required for low-salt sensation. IR76B also codes for a class of GRNs that was previously unrecognized. This class is separate from those that respond to sweet or bitter foods and the loss of IR76b selectively impairs the attractive low-salt pathway, causing low salt to become repellent to the mutant animals.

"The demonstration that IR76b is a Na+ (sodium ion) leak channel suggests an unusual mechanism for activating a sensory neuron," said Montell. "We describe a mechanism for neuronal depolarization that is mediated by a change in the concentration of an extracellular ion (Na+), rather than activation of a receptor or ion channel by a specific agonist, leading to opening of a channel gate."

In other words, the team found it is a channel with a pore that lets sodium pass into the taste cells of the sensilla. For most pores of this type, the gates must be opened by certain key chemical or voltage changes in their environment. This gate, however, is always open, meaning that at any time, sodium can flood into the cell and spark an electrical signal.

"It's an unusual setup, but it makes sense because the local sodium concentration outside taste receptor cells appears to be a lot lower than that surrounding most cells. The taste receptor cells don't need to keep the gate closed to protect themselves from that excess sodium," Zhang says.

The researchers say their findings provide compelling genetic evidence supporting the concept that the opposing behavioral responses to low and high salt are determined largely by competition between two newly identified types of salt-responsive GRNs.

"Not only does this comment on how salt perception may occur in many animals throughout the animal kingdom," Montell said, "but if we can fully understand how aversive and attractive sensory signals work in fruit flies, there may be future potential for controlling insect pests. Fruit flies provide a model for insects that spread disease, so one day we may be able to use thermosensory and chemosensory receptors to provide new strategies to control such pests."