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How the Brain Smells

By studying the olfactory predilections and dislikes of the fruit fly, neuroscientist Chris Potter aims for insights into how the human brain functions.

Fruit Flies mating Image of fruit flies mating by Sarefo

January 2011- After he has sex with her, the male fruit fly swabs his mate with a pheromone. This potent chemical, although invisible to the human nose, is so repugnant to a fly’s antennae that it will repel any other potential suitors for hours.  

Cider vinegar, on the other hand, is so alluring to fruit flies that the insects hasten to it, even if the journey ends in their being pickled.

Johns Hopkins neuroscientist Christopher Potter would like to know how the fly brain processes such olfactory information. More broadly, he is using the fly as a model to understand the workings of the human olfactory brain. Despite their dramatic difference in size, says Potter, “the fly brain and the human brain have pretty much the same underlying architecture for detecting odors. One is a Pinto and one is a Rolls Royce, but the basic parts are the same.”
However, in the brain, little is known about the neurons that make up those parts. “We know what our nose is doing but not what our brain is doing,” says Potter, an assistant professor of Neuroscience. “We don’t know how the signal is turned into disgust or fear. We don’t know how information is interpreted.” Why does the scent of a rose register as a sweet aroma in our brain while rotten garbage gets recorded as, well, rotten? 

One day in his lab, Potter holds a clear plastic tube up to the light to show the recently dissected brain of a fruit fly. Barely visible, the feathery form floats in a transparent liquid. It looks as white and as delicate as a snowflake. This minute brain contains about 100,000 neurons. Potter estimates that about 5,000 of those are dedicated to the sense of smell. Ultimately, he would like to map out the role of each one.

To find those answers, Potter has devised a sophisticated set of genetic tools that allows him to control and monitor the activity of single neurons in the fruit fly brain. The system includes three genetic elements from the fungus Neurospora that the scientists have cloned. Two of the genetic elements can be used together to “turn on” the activity of other genes. Another can be used to “turn off” the activity of other genes. With this genetic toolbox, says Potter, he and his research team can manipulate individual neurons and even suppress their activity altogether. He published a description of the genetic system in the April 30, 2010, Cell.

The genetic toolbox, explains Potter, can also help him begin to connect neurons to behaviors. If neuron A is silenced, for instance, can a fly still detect a whiff of cider vinegar or ripe banana? If neuron B is activated, will a fly still recoil from the scent of fruit fly pheromone?

Answering such questions involves conducting behavioral tests, in which flies are placed in an environment with a scent that the species normally finds pleasing or repellant. In one test, for instance, two glass tubes are placed in a glass jar, with one containing an odorant, such as cider vinegar or fruit fly pheromone, and the other containing a control substance, such as water. Special traps cover the opening of each tube, allowing flies entry but not egress. During an experiment, flies are placed inside the jar and allowed to fly into the tube of their choice.

In tests involving normal fruit flies, most of the insects will fly into a tube of cider vinegar or avoid a tube of pheromone. But if an experiment using a genetically altered group of flies yields a different result, that’s a clue that the neuron in question plays a role in the fly’s ability to detect that particular odor.

Potter, who joined the Neuroscience department last March, is now building the apparatus that he will use for other behavioral tests. Such research could yield practical applications, notes Potter. Learning more nuanced details about the fly brain’s response to various odors could help manufacturers to design superior insecticides.

More broadly, the research may also uncover general principles about how information is transmitted in the brain. “We don’t really understand how our brains take in sensory information and translate it into a perception,” says Potter. “This is one way to understand how they do.” And the way that the fly processes information is going to be generally the same as the way the mouse or the human does, he adds.

–Melissa Hendricks

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