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The Scripps Research Institute News from page 16 fundamental function is, what types of stimuli activate them
under what conditions,” he says. “Translating the learned
Unexplored Neural Circuit information into behavioral execution, through the neurons
in between, that’s where I expect a lot of discoveries in the
Modulates Memory Strength next few years are going to be.”
In addition to Tomchik and Boto, the authors of the study
Learning to avoid negative experiences requires an include Aaron Stahl, Xiaofan Zhang, and Thierry Louis.
interplay of two distinct brain circuits, one to interpret The work was supported in part by the National Institute
“Yikes!” and drive learning, and the other, unexpectedly, of Mental Health, the National Institute of Neurological
to dial in the strength of that memory, a new fruit fly study Disorders and Stroke (R00 MH092294), (R01 NS097237),
shows. and the Whitehall Foundation. Boto and Louis were
“This kind of gain control is probably present in many Neuroscience Scholars of the Esther B. O’Keeffe Charitable
levels of the nervous system, in many organisms,” says Foundation.
Scripps Research neuroscientist Seth Tomchik, Ph.D., lead Seth Tomchik and Tamara Boto About Scripps Research
author of the study. A leading nonprofit biomedical research institute, Scripps
The human brain is comprised of a staggering number a microscope by adding a green fluorescent protein that Research is ranked No. 1 in the world by Nature for scientific
of neurons – about 86 billion, according to recent studies. releases light upon reacting to calcium. Calcium ions are innovation. U.S. News and World Report consistently rank
Given that complexity, neuroscientists working to understand released when neurons communicate. Stimulating the our graduate school in the top 10 in the United States. Our
how learning and memory work begin with simpler model PPL2 neurons during the odor experiments changed the unique structure merges foundational studies in biology,
organisms. Humans and flies share a degree of fundamental brightness of the fluorescence when presented with the odor, chemistry and computer science with translational research
biology, including reliance on the neurotransmitter dopamine an indication that the structures involved in learning and to produce the next generation of drugs and advances in
in learning. memory had altered the degree of response. digital and precision medicine. On campuses in California
“We know with flies, just like in mammals, there are “When we activated this PPL2 set of neurons, it would and Florida, scientists in the institute’s five academic
neurons involved in positive reinforcement, there are neurons actually modulate the strength of that memory,” Tomchik research departments work hand-in-hand with researchers
involved in negative reinforcement – the valence neurons – says. “So, we see there are dopaminergic neurons that encode of the Scripps Research Translational Institute and Calibr,
and then there are this third set,” Tomchik says. “Nobody the aversive stimulus itself, and then there is this additional our drug discovery division. We train the next generation of
really knew what they did.” set that can turn the volume up or down on that memory.” scientific leaders, expand the frontiers of human knowledge
The fruit fly brain contains eight groups of neurons that The ability of PPL2 to strengthen the response was a and accelerate the development of new medicines to improve
produce dopamine. Three of them can be found in what’s surprise, Boto adds. lives around the planet.
known as the fly brain’s “mushroom body.” Humans don’t “I think it is amazing that there is this physiological effect
have an exact analogous brain section, but other brain regions that translates to a behavioral effect,” Boto says. “Dopamine
perform similar functions. In Drosophila melanogaster, aka is not likely to excite on its own, but the response is greater
the fruit fly, the mushroom body is an area highly responsive if it is paired with stimulation of this set of neurons.”
to odors. The study, “Independent Contributions of Discrete
Past fly brain studies have shown that one of the Dopaminergic Circuits to Cellular Plasticity, Memory
dopamine-producing groups projecting into the mushroom Strength and Valence in Drosophila,” appeared May 14 in
body handles desire-inducing memories connected to odors. the journal Cell Reports.
(“Mmmm, rotten bananas!”) while another guides avoidant A next step will be exploring what stimulates PPL2
behavior related to negative experiences. (“Yikes, dangerous neurons and how their activity influences other neurons in
banana smell!”) the memory network, Tomchik says.
To find out the role of the third group, referred to as Studying the brain circuitry underlying experience,
PPL2, research associate and first author Tamara Boto, Ph.D., learning and memory in model organisms can offer insights
trained the flies with an experiment that involved exposing into our own, more complex brains, insights that could help
them to fruit-like odors while simultaneously giving them a us understand issues like addiction, PTSD, depression and
mild electric shock. neurodevelopmental disorders, Tomchik says.
Their conditioned response could be visualized under “We want to understand more about what their

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