Karla Kaun, new assistant professor of neuroscience, has a totally legit reason for knowing that in some trendy bars, people get blotto by inhaling a fine mist of alcohol infused into the air. She employs that same technique to inebriate fruit flies for her studies of addiction. It turns out that the way flies respond to alcohol can inform our understanding of how barflies do too.
The basic neural mechanisms of meeting one’s needs and feeling rewarded are widely found – biologists say “conserved” – among animals. That’s convenient for neuroscience researchers like Kaun because flies are considerably more available and genetically manipulable than people.
“The questions that I really like to address are what’s happening at a very detailed molecular level,” she said. “There are very few models in which you can understand any type of behavior at a neuronal systems level, single neuron level and molecular level. Flies are, I think, a great organism at this point in time to understand these sorts of things.”
Behavior and biology
In experiments over the last dozen years or so, Kaun has demonstrated some surprising behaviors as well as some key biomolecular insights.
In one study, published last year in Science and reported in the New York Times and elsewhere, she and her colleagues showed that flies whose mating advances were routinely rebuffed showed a stronger desire to drink than those who were able to mate successfully. That certainly seems human.
The team traced the behavior to brain levels of a protein called “neuropeptide F,” which was reduced in the brains of the sexually unfulfilled flies. The paper sets up future research on whether the analogous protein in people, “neuropeptide Y,” affects alcohol cravings in people.
In earlier research — the experiments with the ambient alcohol — Kaun showed for the first time that flies do indeed consider moderately heavy alcohol exposure to be rewarding. She paired alcohol exposure with an odor. Then she gave the flies a choice to seek that odor or others. Immediately after sobering up the flies found the odor aversive, but after a day away from booze, they preferred the alcohol-associated odor and continued to for a week. The results appeared in Nature Neuroscience in 2011.
But why do people and flies alike find exposure to drugs and alcohol so rewarding?
“A general theory in the field is that a lot of the pathways involved in addiction-like behavior overlap on the brain’s natural reward pathways,” she said. “Sex is rewarding and food is rewarding because you need both of these to survive, but a lot of the molecular pathways overlap [with drugs and alcohol].”
While drug and alcohol behaviors follow reward pathways, Kaun said, they also interfere with memory and learning pathways in the brain.
“By being drunk and associating something like the feel of a glass in your hand or the context of your favorite bar, you are altering the memory of each of these things,” she said. “You are creating these really salient and long-lasting memories. These memories are what can induce craving feelings.”
Sure enough, in the Nature Neuroscience experiments Kaun found that flies will expose themselves to an electric shock to sniff an alcohol-associated odor, even when they won’t endure that same level of shock to attain sugar (which would actually nourish them). Along the way she and her co-authors tracked the activity of key neurons and the biochemistry governing them, discovering ways to manipulate those interactions to alter certain behaviors.
Garden to ‘Farm’ to Brown
Kaun traces her interest in science to quiet days in the tiny native community of Île-à-la-Crosse in Saskatchewan, Canada. Her parents, one of whom was a teacher, settled there to serve the remote community. Kaun said she would spend time in the garden by the lake, watching nature with a questioning pair of little eyes. She and her mom would perform science experiments together.
Ultimately her parents decided to move her to a somewhat larger town where she could be exposed to a broader education. For college, she enrolled in an interdisciplinary science program at the University of British Columbia, eventually settling into a major in psychology. There she gravitated to the most biologically oriented lab in the department – one that worked with worms.
Her doctoral studies at the University of Toronto, which she completed in 2007, introduced her to genetic and behavioral studies in flies, and when she joined the lab of Ulrike Heberlein first at the University of California–San Francisco and then the Howard Hughes Medical Institute’s Janelia Farm Research Campus, she found her focus on alcohol.
Janelia Farm has attained a global reputation as a major neuroscience research center, but what attracted her and her husband Reza Azanchi, who is her lab manager, to Brown is the quality of its neuroscience program as well.
“Brown has an incredible neuroscience department, I have to say,” she said. “The people at Brown are dedicated to providing great undergraduate and graduate education, involved in cutting-edge interdisciplinary neuroscience research, and really open to collaborations.”
She’s already planning with specific Brown colleagues within and outside the department so that she can continue her detailed investigations of the biological nature of addiction and reward.