By tracking maggots’ food choices, scientists open significant new window into human learning

The squirming larva of the humble fruit fly, which shares a surprising amount of genetic material with the human being, is helping scientists to understand the way we learn information from one another.

Fruit flies have long served as models for studying behaviour because their cognitive mechanisms are parallel to humans’, but much simpler to study.

Fruit flies exhibit many of the same basic behaviours as humans and share 87 per cent of the material that is responsible for genetically based neurological disorders, making them a potent model for study.

While adult fruit flies have been studied for decades, the new paper reveals that their larvae, which are even simpler organisms, may be more valuable models for behavioral research. A fruit fly larva has only 3,000 neurons, for example, while a human has about 10 billion.

The McMaster researchers were able to prove that the larvae, or maggots, are capable of social learning, which opens the door to many other experiments that could provide valuable insights into human behaviour, end even lead to treatments for human disorders, the scientists say.

“People have been studying adult flies for decades now,” explains the study’s lead author, Zachary Durisko. “The larval stage is much simpler in terms of the brain, but behaviour at the larval stage has been less well studied. Here we have a complex behaviour in this even simpler model.”

Durisko and Reuven Dukas, both of McMaster’s Department of Psychology, Neuroscience and Behaviour, have shown that fruit fly larvae are able to distinguish which food sources have been used by other larvae and utilize the information to benefit themselves by choosing to eat from those same established sources instead of available alternatives.

The maggots’ attraction to food that others have been eating is based on smell, and is roughly equivalent to a person arriving in a new city, seeing two restaurants and choosing a busy one over an empty one, the researchers explain.

“They prefer the social over the non-social like we would do, and they learn to prefer the social over the non-social,” Dukas says.

In fact, the motivations may be similar in each case, and could include accepting the judgment of others as an indication of quality and seeking the company of others for protection from harm.

Durisko, the lead author, recently completed his PhD at McMaster, and Dukas, his co-author, is a professor at the university. Their work is published in the prestigious Proceedings of the Royal Society B, one of the society’s biological journals.

The researchers used several combinations of foods, both completely fresh and previously used, and of varying degrees of nutritional value, to compare the maggots’ preferences.

Preventing ‘traffic jams’ in brain cells

Imagine if you could open up your brain and look inside.

What you would see is a network of nerve cells called neurons, each with its own internal highway system for transporting essential materials between different parts of the cell.

When this biological machinery is operating smoothly, tiny motor proteins ferry precious cargo up and down each neuron along thread-like roadways called microtubule tracks. Brain cells are able to receive information, make internal repairs and send instructions to the body, telling the fingers to flex or the toes to curl.

But when the neuron gets blocked, this delicate harmony deteriorates. One result: diseases like Alzheimer’s.

Understanding such blockages and how traffic should flow normally in healthy brain cells could offer hope to people with neurodegenerative diseases.

Toward that end, a research team led by University at Buffalo biologist Shermali Gunawardena, PhD, has shown that the protein presenilin plays an important role in controlling neuronal traffic on microtubule highways, a novel function that previously was unknown.

The research results were published online on May 24 in the journal Human Molecular Genetics. Gunawardena’s co-authors are Ge Yang of Carnegie Mellon University and Lawrence S. B. Goldstein of the Howard Hughes Medical Institute and the University of California, San Diego.

Inside the nerves of fruit fly larvae, presenilin helped to control the speed at which molecular motors called kinesins and dyneins moved along neurons. When the scientists halved the amount of presenilin present in the highway system, the motors moved faster; they paused fewer times and their pauses were shorter.

Given this data, Gunawardena thinks that tweaking presenilin levels may be one way to free up traffic and prevent dangerous neuronal blockages in patients with Alzheimer’s disease.

“Our major discovery is that presenilin has a novel role, which is to control the movement of motor proteins along neuronal highways,” said Gunawardena, an assistant professor of biological sciences. “If this regulation/control is lost, then things can go wrong. This is the first time a protein that functions as a controller of motors has been reported.

“In Alzheimer’s disease, transport defects occur well before symptoms, such as cell death and amyloid plaques, are seen in post-mortem brains,” she added. “As a result, developing therapeutics targeted to defects in neuronal transport would be a useful way to attack the problem early.”

The findings are particularly intriguing because scientists have known for several years that presenilin is involved in Alzheimer’s disease.

Presenilin rides along neuronal highways in tiny organic bubbles called vesicles that sit atop the kinesin and dynein motors, and also contain a second protein called the amyloid precursor protein (APP). Presenilin participates in cutting APP into pieces called amyloid beta, which build up to form amyloid plaques in patients with Alzheimer’s disease.

Such buildups can lead to cell death by preventing the transport of essential materials—like proteins needed for cell repair—along neurons.

The findings of the new study mean that presenilin may contribute to Alzheimer’s disease in at least two ways: not just by cleaving APP, but also by regulating the speed of the molecular motors that carry APP along neuronal highways.

“More than 150 mutations in presenilin have been identified in Alzheimer’s disease,” Gunawardena said. “Thus, understanding its function is important to understanding what goes wrong in Alzheimer’s disease.”

To track the movement of the kinesins and dyneins, the team tagged their cargo with a yellow fluorescent protein. This enabled the scientists to view the molecular motors chugging along inside the neuron under a microscope in a living animal. A special computer program then analyzed the motors’ paths, revealing more details about the nature of their movement and how often they paused.

A how-to manual for fruit fly research has been created

The first ever basic training package to teach students and scientists how to best use the fruit fly, Drosophila, for research has been published. It’s hoped it will encourage more researchers working on a range of conditions from cancer to Alzheimer’s disease to use the humble fly.

The unique scheme has been put together by Dr Andreas Prokop from the Faculty of Life Sciences at the University of Manchester and John Roote from the Department of Genetics at the University of Cambridge.

John Roote said, “In 1910 Thomas Hunt Morgan isolated the first Drosophila sex-linked mutation, white.  Since then many thousands of research workers have realised the potential of the humble fruit fly.

“The powerful research tools that we have today combined with a century of background knowledge, the vast collections of stocks that are available to everyone and the fortuitous ‘pre-adaptation’ of the fly for life in a laboratory ensure that Drosophila melanogaster maintains its position as the pre-eminent model organism for research in genetics.  However, until now a comprehensive teaching programme to guide students through the often daunting first few steps has been surprisingly absent.”

Dr Prokop said: “People don’t realise just how useful the tiny fruit fly can be when it comes to research. Fellow scientists are often not aware of their genetic value for research. For example, about 75% of known human disease genes have a recognisable match in the genome of fruit flies which means they can be used to study the fundamental biology behind complex conditions such as epilepsy or neurodegeneration.”

Fruit flies have been used for scientific research for more than a hundred years. They have allowed scientific breakthroughs in genetics, body structure and function. The first jet lag gene and the first learning gene were identified in flies as well as breakthroughs in neuroscience, such as the discovery of the first channel proteins.

Training package: How to design a genetic mating scheme: a basic training package for Drosophila genetics

Research Institute Study Shows How Brain Cells Shape Temperature Preferences

While the wooly musk ox may like it cold, fruit flies definitely do not. They like it hot, or at least warm. In fact, their preferred optimum temperature is very similar to that of humans—76 degrees F.

Scientists have known that a type of brain cell circuit helps regulate a variety of innate and learned behavior in animals, including their temperature preferences. What has been a mystery is whether or not this behavior stems from a specific set of neurons (brain cells) or overlapping sets.

Now, a new study from The Scripps Research Institute (TSRI) shows that a complex set of overlapping neuronal circuits work in concert to drive temperature preferences in the fruit fly Drosophila by affecting a single target, a heavy bundle of neurons within the fly brain known as the mushroom body. These nerve bundles, which get their name from their bulbous shape, play critical roles in learning and memory.

The study, published in the January 30, 2013 edition of the Journal of Neuroscience, shows that dopaminergic circuits—brain cells that synthesize dopamine, a common neurotransmitter—within the mushroom body do not encode a single signal, but rather perform a more complex computation of environmental conditions.

“We found that dopamine neurons process multiple inputs to generate multiple outputs—the same set of nerves process sensory information and reward-avoidance learning,” said TSRI Assistant Professor Seth Tomchik. “This discovery helps lay the groundwork to better understand how information is processed in the brain. A similar set of neurons is involved in behavior preferences in humans—from basic rewards to more complex learning and memory.”

Using imaging techniques that allow scientists to visualize neuron activity in real time, the study illuminated the response of dopaminergic neurons to changes in temperature. The behavioral roles were then examined by silencing various subsets of these neurons. Flies were tested using a temperature gradient plate; the flies moved from one place to another to express their temperature preferences.

As it turns out, genetic silencing of dopaminergic neurons innervating the mushroom body substantially reduces cold avoidance behavior. “If you give the fly a choice, it will pick San Diego weather every time,” Tomchik said, “but if you shut down those nerves, they suddenly don’t mind being in Minnesota.”

The study also showed dopaminergic neurons respond to cooling with sudden a burst of activity at the onset of a drop in temperature, before settling down to a lower steady-state level. This initial burst of dopamine could function to increase neuronal plasticity—the ability to adapt—during periods of environmental change when the organism needs to acquire new associative memories or update previous associations with temperature changes.

(Image: ALAMY)

Cell biologists show molecular forces are key to proper cell division

Studies led by assistant professor of Biology Thomas Maresca are revealing new details about a molecular surveillance system that helps detect and correct errors in cell division that can lead to cell death or human diseases. Findings are reported in the current issue of the Journal of Cell Biology.

The purpose of cell division is to evenly distribute the genome between two daughter cells. To achieve this, every chromosome must properly interact with a football-shaped structure called the spindle. However, interaction errors between the chromosomes and spindle during division are amazingly common, occurring in 86 to 90 percent of chromosomes, says Maresca, an expert in mitosis.

“This is not quite so surprising when you realize that every single one of the 46 chromosomes has to get into perfect position every time a cell divides,” he notes. The key to flawless cell division is to correct dangerous interactions before the cell splits in two.

Working with fruit fly tissue culture cells, Maresca and graduate students Stuart Cane and Anna Ye have developed a way to watch and record images of the key players in cell division including microtubule filaments that form the mitotic spindle and sites called kinetochores that mediate chromosome-microtubule interactions. They also examined the contribution of a force generated by molecular engines called the polar ejection force (PEF), which is thought to help line up the chromosomes in the middle of the spindle for division. For the first time, they directly tested and quantified how PEF, in particular, influences tension at kinetochores and affects error correction in mitosis.

“We also now have a powerful new assay to get at how this tension regulates kinetochore-microtubule interactions,” Maresca adds. “We knew forces and tension regulated this process, but we didn’t understand exactly how. With the new technique, we can start to dissect out how tension modulates error correction to repair the many erroneous attachment intermediates that form during division.”

Valuable Tool for Predicting Pain Genes in People: ‘Network Map’ of Genes Involved in Pain Perception

Scientists in Australia and Austria have described a “network map” of genes involved in pain perception. The work, published in the journal PLOS Genetics should help identify new analgesic drugs.

Dr Greg Neely from the Garvan institute of Medical Research in Sydney and Professor Josef Penninger from the Austrian Academy of Sciences in Vienna had previously screened the 14,000 genes in the fruit fly genome and identified 580 genes associated with heat perception. In the current study, using a database from the US National Centre for Biotechnology Information, they noted roughly 400 equivalent genes in people, 35% of which are already suspected to be pain genes.

The map they constructed using fly and human data includes many known genes, as well as hundreds of new genes and pathways, and demonstrates exceptional evolutionary conservation of molecular mechanisms across species. This should not be surprising, as every creature must be able to identify a source of pain or danger in order to survive.

Comparing fly with human data, they could see that a particular kind of molecular signaling (phospholipid signaling), already implicated in pain processing, appeared in the pain network. Further, they demonstrated the importance of two enzymes that make phospholipids, by removing those enzymes from mice, making them hypersensitive to heat pain.

"Pain affects hundreds of millions of people, and is a research field badly in need of new approaches and discoveries," said Dr Neely.

"The fact that evolution has done such a remarkable job of conserving pain genes across species makes our fly data very useful, because much of it translates to rodents and people.

"We are able to test our hypotheses in mice, and if a gene or pathway or process functions as we predict, there is a good chance it will also apply to people.

"By cross-referencing fly data with human information already in the public domain — like gene expression profiling or genetic association studies — we know we’ll be able to pinpoint new therapeutic targets."