Uncannily, fruit flies appear in Texas research news, time and time again, as their physiology and behavior offers many different applications in life sciences research. Recently, researchers at the University of Houston (UH) have taken a step forward in elucidating the mechanisms of Pavlovian conditioning in a fruit fly model. The new research is helping to understand how memories form and ultimately this will provide better therapies to enhance human memory at all ages including individuals with dementia.
A new article has just been published in the November 27 issue in Current Biology entitled “Presynaptic Inhibition of Gamma Lobe Neurons is Required for Olfactory Learning in Drosophila” by Gregg Roman, an associate professor of biology and biochemistry at UH, and Shixing Zhang, his postdoctoral associate, that describes their findings.
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Roman points out that memory is a daily function and central to our sense of self and that we are the sum of our experiences. If we have problems generating new memories or have difficulty retrieving memories, existence is changed forever. Further research should enhance our understanding of how memories form.
By studying the brains of Drosophila (fruit fly), Roman and Zhang hope to elucidate some of these mysteries. Neurons that are involved with smell (olfactory) learning and memory are a good example of classical conditioning that was first described by Pavlov and his dog experiments. Roman and Zhang have established a fruit fly model where they have trained flies to associate a weak electric shock with a particular smell. Once the flies are trained, they avoid that particular smell.
The researchers discovered that gamma lobe cells of the mushroom bodies are activated by smells. By training fruit flies to associate a smell with an electrical shock, alters how the cells respond to certain smells. Altering gamma lobe neuron activity generates a memory trace. They observed that training gamma neurons caused them to be more weakly activated by smells that were not paired with electrical shock. Therefore, gamma neurons respond stronger to a trained smell than to an untrained smell.
Roman and Zhang were also able to identify a protein, the heterotrimeric G(o) protein, which is involved in inhibiting gamma neurons. When they removed the activity of the G(o) protein within the gamma neurons, they observed a loss of the memory trace which in turn exhibits poor learning. This protein is involved with inhibiting neurotransmitter release from gamma neurons. This protein is necessary for forming a memory trace and associative memories.
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The rationale of using fruit flies to understand memory traces and associative learning is such that their brain is simpler in structure with fewer neurons. Additionally, the mushroom body is similar to the perirhinal cortex in humans. The human perirhinal cortex is involved with sensory integration and learning. The simplicity of the fruit fly brain allows for easier acquisition on how memories are established, stored and retrieved. Roman comments, “Drosophila represents the Goldilocks principle of neural research, with sufficient behavioral complexity, while maintaining a huge advantage in neural simplicity. 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”.
Roman and Zhang believe that their experience indicates that molecules and logic observed in this model will translate to other animals including humans providing for a better understanding of how memories work in humans not only at the molecular level but at the neural circuit level as well.
Photo from bbc.co.uk