Fly on the Wall

Making fly science approachable for everyone

Month: February 2015

Breaking Research: Separable short- and long-term memories can form after a momentous occasion

When was your first kiss? What were you doing the last time you heard life-changing news? After only a single experience, your brain was somehow able to form a long-term memory of these events. This phenomenon has baffled neuroscientists for decades, but in a recent paper published in PNAS, Yamagata et al. report a surprising discovery that may finally provide some answers.

Scientists have long thought that memory storage follows a standard path: short-term memory is stored in one part of the brain, then eventually strengthened and transferred into long-term storage somewhere else. This transfer from short- to long-term memory typically requires repetition (think of memorizing song lyrics or studying for an exam). So how, then, does your brain form a long-term memory after a single momentous event?

training paradigmFigure 1. Flies can learn that a particular odor is associated with a reward. (1) Fly trained with odor and sugar reward, (2) Fly trained with odor and researcher-activated reward neurons.

Imagine that you are a starving fruit fly, desperately searching for food in a new area. Suddenly, you encounter a mysterious new odor and discover a nearby source of life-sustaining food. After a single experience such as this, flies can instantly form an association between that new odor and food, and will follow the odor if it encounters it again (Figure 1-1). Yamagata et al. took advantage of this instinctual behavior to study how the fly brain stores a long-term memory after one event.

They trained groups of flies to associate a particular odor (A) with a sugar reward by presenting them with both stimuli at the same time. They confirmed that the flies formed a memory by giving them a choice between odor A and a different odor (B), and found that flies preferably flocked to an area scented with odor A.

They also identified a large group of dopamine neurons (known as PAM neurons) that were activated by the sugar reward. If the researchers activated the PAM neurons instead of providing sugar when the flies encountered odor A, the flies still associated that odor with a reward (Figure 1-2).

Now the question: how does PAM neuron activity paired with an odor form a long-term memory?  The researchers found that the PAM neurons could actually be grouped into two types. When they activated one type, which they dubbed stm-PAM, the flies only formed a short-term memory. The researchers tested their memory immediately after training and found most of the flies hanging around odor A. But 24 hours later, the memory was gone.

Surprisingly, when the researchers activated the other type of PAM neurons during training (called ltm-PAM), the flies only formed a long-term memory! The flies weren’t particularly interested in odor A immediately after training, but 24 hours later the flies flocked toward it. This incredible result showed that long-term memory doesn’t necessarily require a short-term counterpart. So, instead of the reward pathway forming a short-term memory that later transforms into a long-term memory, this sugar reward formed two complementary memories.

separable memory componentsFigure 2. Long-term memory (LTM) doesn’t always form from short-term memory (STM). In some cases, STM and LTM form independently, with STM degrading over time, and LTM progressively strengthening.

How can you have a long-term memory without a short-term memory? Imagine again that you are a starving fly, and you just ate something that didn’t taste very good. You’ve moved on, but later realize that you feel satisfied and energetic. You didn’t form a rewarding short-term memory because the food wasn’t very tasty, but now you have a positive long-term memory because it was nutritious. This is precisely what the researchers discovered when they investigated the PAM neurons further.

The researchers trained the flies using arabinose, an artificial sweetener that tastes sweet but isn’t nutritious, and sorbitol, a nutritious but tasteless sugar. Flies that ate arabinose formed a short-term memory that required stm-PAM activity, while the flies that ate sorbitol formed a long-term memory that required ltm-PAM activity. Thus, the researchers found that the PAM neurons seem to carry two separate pieces of information about the sugar reward: a “delicious” signal, which creates a short-term rewarding memory, and a “nutritious” signal, which creates a long-term memory.

These findings show that long-term memory doesn’t always form from a short-term memory. Instead, they can be independent processes created from different information signals about the same stimulus, such as taste and nutrition from sugar. In humans, our rewards are even more complex (such as the feelings associated with your first kiss), and our memory system likely works in a similar way.

Now, how can I apply this strategy while studying for my next exam?

 

 

 

 

 

 

Reference:

  • Yamagata N., Yoshinori Aso, Pierre-Yves Plaçais, Anja B. Friedrich, Richard J. Sima, Thomas Preat, Gerald M. Rubin & Hiromu Tanimoto (2014). Distinct dopamine neurons mediate reward signals for short- and long-term memories, Proceedings of the National Academy of Sciences, 112 (2) 578-583. DOI: http://dx.doi.org/10.1073/pnas.1421930112

Valentine’s Day Special: Drosophila in lust

Valentine’s Day is quickly approaching, which means that men (and women) all over the U.S. are performing courtship rituals to woo a companion. But while we humans often have trouble figuring out the right moves to attract a potential mate, fruit flies have it down to a science. And incredibly, researchers can study fruit fly courtship to gain a better understanding of our own brains.

Fly courtshipThe fruit fly courtship ritual has a set of specific steps. Image modified from Greenspan and Ferveur, 2000.

In polite fruit fly society, males have the responsibility of wooing a female. The mating behavior is composed of several specific steps (see figure), which the males perform in repetition until the female responds (or until the male gives up trying). This courtship behavior is very well understood by researchers, due in part because the courtship ritual is so stereotyped and predictable. Courtship is a complex innate behavior, which means that all flies are born with the knowledge of how to do it. Successful mating means passing your genes on to the next generation, so the networks of neurons responsible for this behavior are critical for survival and therefore consistent among flies. This consistency provides a perfect system for studying how neurons interact to give rise to a behavior.

Fly researchers have made great progress in unraveling the anatomy underlying courtship, and found that the behavior arises from the integration of multiple sensory cues, including smell (is the female releasing “come and get me” pheromones?), vision (does the female look interested?), and touch (am I in the right spot?). The fruit fly brain has to combine all of this information to influence the fly’s decision making. Should he start the next step of the courtship ritual, or try this one again? Can he approach the female and try to mate?

“But who cares about fruit fly sex?” you might ask. The fly researchers studying courtship aren’t necessarily interested in exactly how flies get it on. They’re more interested in a general understanding of how the brain integrates multiple sensory cues to influence decisions. The fact that the “courtship circuit” is critical for survival suggests that it is also used by other important behaviors, and is shared by other species. Think about how much information needs to be integrated for you to hunt for food, drive a car, or even court another human. The complexity is amazing… how does our brain manage that?!  By first studying it in the simpler brains of fruit flies, we can gain a basic understanding that we can apply to our complex mammalian brains.

Studying courtship behavior can provide us with an understanding for how neurons communicate and integrate information to make decisions, but researchers can do even more with it. As our understanding of courtship increases, we can use it to investigate other behaviors that seem more directly related to human health, such as learning and memory, sleep, and addiction.

For example, the courtship ritual is most commonly used to study memory. Researchers have noticed that male flies tend to “give up” after too many rejections, so they’ve developed a learning experiment that exposes males to uninterested females. Normal males quickly learn to give up on trying to mate with them, but what happens if a scientist mutates a particular gene or “turns off” a certain molecule? Now researchers can use courtship to investigate the genes and molecules involved in learning and memory. If a mutant male never learns to stop courting, the gene might be involved in learning. If the mutant male initially learns to give up, but then quickly forgets the experience and tries again, the gene might be involved in long-term memory.

The predictable steps of courtship also allows researchers to easily recognize when a male is impaired in this innate behavior, providing a system for studying brain development. Last year, the Seghal lab published a study in which they used courtship behavior to show that sleep is necessary for normal brain development. They deprived young flies of sleep and found that, as adults, the flies were impaired in courtship. The impairment was due to lack of growth in a brain region important for the behavior, suggesting that sleep deprivation stunts brain development.

As a final example (and one of my favorites), in 2012 the Heberlein lab produced a paper showing that sexual rejection makes male flies turn to booze. Natural rewards such as sex activate the brain’s reward system, which is also activated by abused drugs and alcohol (did you know that flies can be alcoholics too?). Understanding how natural rewards, drugs, and rejections affect the reward system is important for treating or preventing addiction. From this study, the researchers in the Heberlein lab found that levels of neuropeptide F (NPF), a signaling chemical, rose and fell with reward and rejection. Low levels of NPF drove flies to drink, and artificially raising NPF levels prevented this behavior. Their finding that the same chemical is involved in both natural and artificial rewards directly helps research aimed at understanding a similar chemical in mammals called NPY.

In these research examples, the goal of studying courtship wasn’t to learn about fruit fly sex, it was to use what we know to answer more important questions. Because of these studies, researchers have identified dozens of genes and molecules involved in learning and memory, uncovered more reasons for why sleep is important, and progressed our understanding of how alcohol affects the brain. All of these findings have direct implications for human health because we also share those memory genes, need sleep, and use drugs and alcohol.

Flies in love

So the next time you see some flies getting it on near your bananas… swat them, because they’ll make hundreds of new nuisances for you to deal with. But afterward, you can smile knowingly to yourself and remember that scientists are studying the act to answer long-standing questions in neuroscience.

 

 

General references:

  • Pavlou H.J. and S.F. Goodwin (2013). Courtship behavior in Drosophila melanogaster: towards a ‘courtship connectome’, Current Opinion in Neurobiology, 23 (1) 76-83. DOI: http://dx.doi.org/10.1016/j.conb.2012.09.002
  • Griffith L.C. and A. Ejima (2009). Courtship learning in Drosophila melanogaster: Diverse plasticity of a reproductive behavior, Learning , 16 (12) 743-750. DOI: http://dx.doi.org/10.1101/lm.956309

“Why do we have to learn this stuff?” — establishing Drosophila as a MODERN teaching tool in schools

This guest post is written by Dr. Andreas Prokop from the University of Manchester. He is passionately engaged in Drosophila-related outreach activities and science communication and writes here about the importance of using fruit flies in the classroom and calls on other fruit fly researchers to help develop strategies to achieve this goal.

Drosophila clearly is the animal in which biology is conceptually best understood. But how well do we sell this fact to the public and in schools? Certainly, Drosophila is far more than an animal substitute for Mendel’s peas, and the recent post by Bethany gives wonderful examples of what can be done with flies as modern and effective teaching tools in class rooms. The enormous power of bringing Drosophila into schools becomes unmistakably clear when talking to members of the public: those who experienced flies in schools, even decades ago, tend to respond with noticeably greater curiosity and interest to fly-related topics than those without such memories. Importantly, there are many biology specifications of the curriculum that can be explained extremely well using flies – and this can usually be spiced up with exciting, simple and cheap experiments that are likely to stick in pupils’ minds for the future. However, in this scenario, flies should not necessarily dominate but rather be used as teaching tools wherever they can help teachers to achieve a lesson’s learning objectives. Learning modern biology through flies, shoulder-to-shoulder with related human examples, clearly conveys the value of simple invertebrate model organisms without any further need to emphasise and explain. If we can establish flies in this way as modern teaching tools in schools, this will in the long term be more powerful than labour-intense Drosophila days at schools organised by scientists, and will have a chance to be applied on a far larger scale.

In Manchester, we are experimenting with the above ideas very successfully. However, it has become clear that a key challenge is the creation of resources for teachers. Such resources will only work if they are concise, explained in simple terms and conceptually mature, so that they meet the needs of busy teachers in each and every aspect and help them gain quick understanding which they can then pass on to their students. To acquire the necessary expertise for this task, we have started to place PhD students for several weeks as active teacher assistants in schools, which allows them to experience school realities first, before generating adequate and tailor made resources. However, this is only one strategy and more effort is needed. It would therefore be great if other members of the fly community contributed, thus generating a wider choice of materials to meet the individual needs and personal tastes of a greater range of teachers. If you are interested in this kind of activity and are attending the American Drosophila Research Conference in 2015 in Chicago, please come to the Drosophila science communication workshop to discuss possible strategies.

Clearly, long-term strategies are needed if we want to promote the wider understanding of invertebrate model organisms, thus also addressing the current downturn in Drosophila funding recently highlighted by Hugo and his colleagues. Tragically, this decline occurs in times where Drosophila research is perhaps more urgently needed than ever, when considering that Human Genetics and “omics” approaches bring up more questions than could possibly be answered without the fly. Starting in schools addresses this problem at its roots and lays important foundations for the future. But there is also personal benefit from these activities: engaging with the public in any way (and this clearly includes engagement at schools!) helps to develop the right arguments that work with members of the public – hence, naturally, also with members on grant panels! In my experience, it forces one to think about the essentials of one’s science leading to new ideas and thoughts, thus becoming a win-win activity that pays off in two directions.

 

Fly Human ComparisonWhy Drosophila can be used to explain fundamental and even human biology or biology of disease: Humans share a surprising amount in common with Drosophila. In particular, the genes that tell cells how to divide, develop, and function and what the basic body plan should look like are often the same as in humans. This new understanding yielded a wealth of exciting discoveries – even about the brain and the processes of learning and memory – and about mechanisms of disease (taken from the short educational film “Small fly – BIG impact“)

 

Interesting links:

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