Let’s not forget the fruit fly

Might want to think twice before you swat that fruit fly buzzing around your kitchen, suggests Ronald Davis, Ph.D., chairman of the neuroscience department at Scripps Florida in the Jupiter campus, who is researching the genes required in learning and memory.

ron davis small
Scripps scientist Ron Davis

Consider this, Davis said: “The fly has 15,000 genes. Humans have 25,000 genes, so we are not that different.”

But, thank goodness (for the researchers), the fruit fly’s brain is smaller.

“The human brain has 100 billion neurons – that’s about as many stars in the Milky Way,” he said. “On top of that, each neuron makes 10,000 connections. That’s an amazing social network of cells.”

Meanwhile, the brain of the fruit fly has 100,000 neurons.

“Its brain is a million times less complex than the human brain,” Davis said. “Even 100,000 neurons is hard to grasp, but we can start working with that.”

Figuring out how memories are formed and learning takes place are monumental tasks, when you think about it – even if all those 100 billion neurons fired at once.

“The human brain, a three-pound mass of tissue, captures memories across our lives  – many, if not all, of our episodes and stories in a biological form — and recalls them, and we don’t know how that happens,” Davis said.

“We can’t understand how the brain forms and encodes memories,” he continued. “Our brain is too complex a network to wrap our brains around. So, to simplify, we use the fruit fly. It is an incredible model to understand the subset of genes in memory formation because its genes are conserved (there are similar genes in the fruit fly, mouse, rat and humans), so hopefully, the principles we learn from the fruit fly can be applied to other organisms, including humans.”

To meet that challenge, the scientists introduced a strategy to identify the genes involved in memory.

Step one: “We can teach flies simple tasks,” Davis said. “We present them with an odor and give them a mild electric shock. They learn quickly and run away. Or, we give them a positive stimulus, and they run toward it.”

The second major step in the strategy is to isolate the mutant flies that can’t learn or remember.

“We can identify sets of genes or mutant strains in those mutant animals, and pull those genes out of the flies and study them on the DNA level,” he said. In addition, “genes encode proteins, so we can then deduce what brain proteins that gene makes and how it is involved in memory formation.”

The scientists’ final overall strategy is to identify each gene in a fly that has to do with memory formation.

“Out of 15,000 genes in a fly’s DNA, there are 400 or 500 genes that are important to learning and memory,” Davis said. “We have about 100 genes that we know about right now.”

Once the scientists have a handle on that, they hope to reconstruct how the molecular machinery within neurons for memory works.

That may sound complicated, but machinery is machinery, he explained.

“It’s a little like a ’63 Stingray,” he said. “Without knowing anything about the car, you can disassemble it and deduce what different parts do.”

Same with isolating genes. If you are missing the gene equivalent of the car starter, you can’t learn. If you are missing the equivalent of the spark plug, you’ll start, but you won’t hit on all eight cylinders.

If you take something like the radiator out, the car (or you) will run great, but only for five minutes.

“The radiator would be the equivalent to a maintenance function,” he said.

The headlights, however, don’t affect the running of the car, one way or another, and you still can function with your eyes closed.

“In the same way, we can identify mutants in fruit flies that can’t learn like “normal” flies, or we can identify flies that can learn, but can’t maintain or remember,” he said.

“An amazing aspect — something that surprises a lot of people — fruit fly genes are conserved – if we isolate a fruit fly gene, there’s 99 percent certainty that we can identify that same gene in humans, and it is involved in human behavior, at least.

Take the gene, dunce, for example. When it is mutated in fruit flies, they have a learning deficiency. The human counterpart of dunce is involved in regulating mood. In the last five years, scientists have found that humans who carry a certain variation of the human dunce gene have an increased susceptibility to schizophrenia.

Another example: When the gene NF1 is mutated in fruit flies, they can’t learn. Humans with the condition, neurofibromatosis type 1, have a mutation of NF1, and about half of them have difficulty in learning or attention deficiency.

And here’s an example of an ongoing study with humans: The scientists obtained DNA from 2,000 subjects with bipolar disorder, and they took 80 fruit fly and mice genes that are involved in memory. Then, they studied those 80 genes in the individuals with bipolar disorder, as well as comparing those genes relative to a control group with no history of psychiatric disease to see whether there were unique changes, variations or mutations.

“So far, we’ve hit a few novel genes,” Davis said. “If we find a change in a fair fraction in the bipolar group in some gene, and we don’t find it in the normal population, that leads to the conclusion that changes in that gene in the DNA might confer an increased probability that an individual will be subject to bipolar disorder.”

The goal of memory and learning research is to better understand the disorders that impact memory and learning, he said.

“Memory issues form a common thread in major neurological and psychiatric illnesses and so has profound medical importance,” he said.

Alzheimer’s disease, which affects 5 million people and is hereditary, is the obvious disease that comes to mind, but people with schizophrenia, which affects one percent of the population, have a deficiency in forming memories. People with autism spectrum disorder have problems learning complex tasks. Drug addicts have memory problems – going back to the place where they shoot up, for example, leads to relapse — as well as people suffering from mood disorders, like bipolar and depression.

People with Attention Deficit Hyperactivity Disorder and those who have suffered brain trauma have memory problems. And, then, there are the memory problems that come along with normal aging – where are those car keys?

“The end game has to be to solve these diseases,” he said. “Just imagine if we took all the genes involved in memory behavior, and through Scripps’ drug-discovery program, if can we find drugs that can tweak the activity of those proteins involved (in memory and learning) and make them work better, these drugs would be cognitive enhancers. Right now, we need as many cognitive enhancers as we can get.”

written for palm2jupiter

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