A new roadmap

JUPITER, Fla.—Recently, Scripps Research published results from a study on the nervous system of fruit flies. The study, supported in part by the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and the Whitehall Foundation, is available online in the journal Cell Reports. Using fruit flies as model organisms, it focuses on neural conditioning and memory strength, which are modulated by groups of neurons in the brain. It is generally accepted that different neurons are responsible for negative and positive reinforcement respectively, but there has been relatively little known about a third type of neurons present in the brains of many organisms.

Recent studies estimate the number of neurons in the human brain at approximately 86 billion. Due to this level of complexity, research will initially deal with simpler models. A number of fundamental physiological similarities between humans and flies, including a reliance on the neurotransmitter dopamine in learning, make them an ideal candidate for these studies.

The fruit fly brain produces dopamine using eight groups of neurons in a part of the brain called the “mushroom body,” which is highly sensitive to odors. This brain region doesn’t exist in the human brain, but functions very similarly to parts of the human brain. Previous studies have shows that one group of dopamine-processing neurons deals with positive memory-inducing signals to cause feelings of desire, and another deals with negative memory-inducing signals to cause feelings of avoidance.

In order to study the third group of neurons in fruit flies, referred to as PPL2, research associate and first author Dr. Tamara Boto, trained the flies with an experiment that involved exposing them to fruit-like odors while simultaneously giving them a mild electric shock. The conditioned response to this stimulation could be viewed through a microscope using a green fluorescent protein that reacts to calcium—which is released when neurons communicate—by releasing light. Researchers noticed that stimulating the PPL2 neurons during the experiments changed the brightness of the fluorescence, an indication that the structures involved in learning and memory had altered the degree of response. It is interesting to note, however, that this stimulus had no effect on behavioral reinforcement, suggesting that different sets of dopaminergic neurons modulate olfactory valence and memory strength via independent actions on a memory-encoding brain region.

“When we activated this PPL2 set of neurons, it would actually modulate the strength of that memory,” said Scripps Research neuroscientist Dr. Seth Tomchik, lead author of the study. “So we see there are dopaminergic neurons that encode the aversive stimulus itself, and then there is this additional set that can turn the volume up or down on that memory.”

“I think it is amazing that there is this physiological effect that translates to a behavioral effect,” Boto added. “Dopamine is not likely to excite on its own, but the response is greater if it is paired with stimulation of this set of neurons.”

The next step, according to Tomchik, is to explore what stimulates PPL2 neurons and how their activity influences other neurons in the memory network. He added that the opportunity to study the brain circuitry underlying experience, learning and memory in model organisms has the ability to offer insights into our own, more complex brains. These insights may help us understand issues like addiction, PTSD, depression and neurodevelopmental disorders.

“We want to understand more about what their fundamental function is, what types of stimuli activate them under what conditions,” he says. “Translating the learned information into behavioral execution, through the neurons in between, that’s where I expect a lot of discoveries in the next few years are going to be.”

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