Using Fruit Fly Models to Study Memory Disorders

Dementia is currently one of the leading causes of disability and dependency among older people worldwide, and Alzheimer’s disease is one of the key causes of dementia. Alzheimer’s causes loss of memory and other important mental functions such as behavioral and social skills. Alzheimer’s is thought to be caused by accumulation of plaque in the brain – “plaque” being protein clumped together that disrupts brain function .

Scientists have been working to find a cure for dementia for a very long time. One method used to develop potentially helpful drugs and treatments against Alzheimer’s and other dementia is in vivo testing. In vivo testing entails finding a living biological system which can model the effects of the treatment on the disease. Unfortunately, in vivo testing can be difficult to perform, expensive and raise ethical questions. It is also unclear how well conclusions from in vivo experiments in a non-human animal will translate to human health.

Fortunately for the study of memory disorders, researchers at Cambridge University and Johns Hopkins University have fully mapped out the brain of a fruit fly larva, an animal commonly used for in vivo models of memory disorder.

“From our study alone, it is hard to say too much about disorders, since we were looking at one individual for that experiment. Once you know what individuals look like, in the future, you can see what would happen if you knocked out one gene. So this is the predecessor to such work.” 

Dr. Ben Pedigo

This map, known as a “connectome” was created by cutting thin slices from the brain of a fruit fly larva. These slices were then scanned using a powerful microscope, known as an electron microscope, and the images analyzed to chart the 548,000 connections between nerve cells (also known as neurons), called synapses. The researchers found the synapses by locating areas with abundant numbers of vesicles, tiny balloons containing chemical neurotransmitters that enable electrical transmissions carrying information to jump from one neuron to another.

Before the Cambridge-Johns Hopkins work to detail the fruit fly neural network, the last connectome completely mapped was that of a flatworm, a highly simplistic organism with only a few hundred neurons. The fruit fly connectome is a huge leap forward from this work. As the first connectome of a behaviorally complex organism, it enables great insight into the inner workings of the fruit fly’s mind and behavior – showing how the network works naturally and is impacted by other factors. For example, some scientists found two neurons, dubbed “Moonwalker neurons,” which, when triggered, would cause the fly to stop all other activities and walk backwards! Most behaviors are far more complicated however, and the result of a multitude of interconnected neurons.

With the map of the fruit fly connectome now available, scientists could potentially gain the ability to better define and understand memory disorders in fruit fly brains. However, the Cambridge and Johns Hopkins researchers say more work is needed before that can happen, because having only a single connectome makes it difficult to gain enough data on how the brains of fruit flies with disordered memory differs from healthy ones. 

According to Ben Pedigo, a scientist at the Allen Institute for Brain Science who worked on this study as a graduate student at Johns Hopkins University: “From our study alone, it is hard to say too much about disorders, since we were looking at one individual in that experiment. Once you know what individuals look like, in the future, you can see what would happen if you knocked out one gene. So, this is the predecessor to such work.” 

Pedigo adds that the pattern of connections mapped in their work are thought to be the main mechanism the brain uses to store memories. He also says that more connectomes are on the way, since the work of creating connectomes is becoming easier to expand to other animal models and will be easier to replicate in more labs for less money. 

As more institutions begin to try their hand at creating connectomes, scientists may soon have more models of animal brains relevant to the study of different human diseases. For example, the adult fruit fly connectome was also recently completed and the federal government’s National Institutes of Health (NIH) is funding the Allen institute’s efforts to produce the connectome of a mouse. This, researchers say, will be the most advanced animal to have its brain mapped out, and is an animal far closer to humans on the evolutionary tree. This work will open new doors for the advanced study of human memory disorders. There is hope for people with dementia.