Do fruit flies hold the key to treating dementia? Researchers at the University of
Houston (UH) have taken a significant step forward in unraveling the mechanisms of
Pavlovian conditioning. Their work will help them understand how memories form and,
ultimately, provide better treatments to improve memory in all ages. 
“Memory is essential to our daily function and is also central to our sense of self,”
Roman said. “To a large degree, we are the sum of our experiences. When memories can
no longer be retrieved or we have difficulty in forming new memories, the effects
are frequently tragic. In the future, our work will enable us to have a better understanding
of how human memories form.”
Roman and Zhang set about to unravel some of these mysteries by studying the brains
of fruit flies (Drosophila). Within the fly brain, Roman says, there are nerve cells
that play a role in olfactory learning and memory. Olfactory learning, he says, is
an example of classical conditioning first described by Pavlov in his experiment with
dogs. In their study, the flies were trained to associate a weak electric shock with
an odor. After training, the flies avoided that odor.
“We found that these particular nerve cells – the gamma lobe neurons of the mushroom
bodies in the insect brain – are activated by odors. Training the flies to associate
an odor with an electric shock changed how these cells responded to odors by developing
a modification in gamma lobe neuron activity, known as a memory trace,” he said. “Interestingly,
we found that training caused the gamma lobe neurons to be more weakly activated by
odors that were not paired with an electric shock, while the odors paired with electric
shock maintained a strong activation of these neurons. Thus, the gamma lobe neurons
responded more strongly to the trained odor than to the untrained odor.”
The team also showed that a specific protein – the heterotrimeric G(o) protein – is
naturally involved in inhibiting gamma lobe neurons. Roman says removing the activity
of this protein only within the gamma lobe neurons resulted in a loss of the memory
trace and, thus, poor learning. Therefore, inhibiting the release of neurotransmitters
from these neurons through the actions of the G(o) protein is key to forming the memory
trace and associative memories. 
“Drosophila represents the Goldilocks principle of neural research, with sufficient
behavioral complexity, while maintaining a huge advantage in neural simplicity,” Roman
said. “The complex behaviors allow us to examine many behavioral processes like learning,
attention, aggression and addiction-like behaviors, while the simplicity allows us
to dissect the crucial neural activities down to single cells. Additionally, Drosophila
has the most powerful genetic toolkit available for behavioral experimentation. In
using these tools, we are genetically identifying the molecules necessary to perform
these behaviors and dissecting the logic of the neural circuits that allow for changes
in behavior to occur.”
The pair says all their experience to date suggests the molecules and logic will translate
to most animals, including humans, leading to a more complete understanding of how
memories form in humans, both at the level of molecules and through the activity of
neural circuits.
Initially funded by a Norman Hackerman Advanced Research Program award from the state
of Texas, a Major Research Instrumentation Program grant from the National Science
Foundation was also critical, supplying the microscope necessary for measuring neural
activity.
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