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BrainFacts.org

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Creation Date: 9 March 2012 | Review Date: 9 March 2012

Animal Models

Did you know even animals with simple nervous systems can help us learn about how our own nervous system works? The sea hare has helped scientists understand learning and memory, and fruit flies have led to breakthroughs in our knowledge of depression. Studying brain diseases in mice or monkeys helps us grasp the nature of a disease, as well as the impact of various interventions. Each animal used in the study of neuroscience has benefits and drawbacks.

A roundworm, also known as Caenorhabditis elegans
Roundworms are used to study communication between neurons. Credit: (2005) The Evolution of Self-Fertile Hermaphroditism: The Fog Is Clearing. PLoS Biol 3: e30. doi:10.1371/journal.pbio.003003.
A sea hare, also known as aplysia
Even sea hares can learn, and Eric Kandel, MD, used them to conduct his Nobel Prize winning research on learning and memory. Courtesy, with permission: Thomas Carew, University of California, Irvine.
Fruit flies battle each other for control over territory
To learn about depression, scientists have made an interesting choice — the fruit fly. Courtesy, with permission: Kravitz laboratory, Harvard Medical School.
Zebrafish, also known as Danio rerio
What fish have transparent eggs, allowing scientists to watch as the embryo inside grows and develops? Zebrafish. Courtesy, with permission: Robert Fisher, Standford Neurology and Jaimie Henderson, Stanford Neurosurgery.
Zebra finch, also known as Taeniopygia guttata
How can birds help us learn about the development of language? Credit: Adar E. et al. (2008) The Relationship between Nature of Social Change, Age, and Position of New Neurons and Their Survival in Adult Zebra Finch Brain. The Journal of Neuroscience 28:5706-07.
Mice and rats, also known as Mus musculus and Rattus norvegicus
Mice and rats are the most commonly used vertebrates for research, and have advanced knowledge in almost every area of neuroscience research. Credit: Garami A. et al. (2011) Thermoregulatory Phenotype of the Trpv1 Knockout Mouse: Thermoeffector Dysbalance with Hyperkinesis. Journal of Neuroscience 31:1561-1933.
A Briard dog at the U.S. Capitol building

Intelligent animals help scientists better-understand hearing, vision, and other senses. Briard dogs are prone to a genetic form of blindness. Once treated with gene therapy, visually impaired Briards showed improved vision. Today, Lancelot (shown) continues to see well after a single gene therapy treatment.

Courtesy,with permission: Foundation for Fighting Blindness.
A monkey feeds itself with a brain-controlled prosthetic arm.

Research with non-human primates is not done often, but for some areas of neuroscience, it can be vital.

Motorlab, University of Pittsburgh School of Medicine.
A woman helps her daughter ride a bike

Are humans ever used for research? Yes, they are!

Copyright Dynamic Graphics/Jupiterimages.

Although an invertebrate with a primitive brain, the nematode (C. elegans) has a nervous system that uses neurotransmitters, receptors, and signaling pathways similar to those in the human brain. What's more, C. elegans shares about 21 percent of their genes with humans.

Scientists have studied the development of the C. elegans nerve cells extensively and found that adults have 302 neurons.  Therefore, scientists have been able to map the connectivity between these neurons with precision, enabling them to match individual functions to neurons and their networks.

Another plus: C. elegans is very small (about 1 millimeter or, 0.04 of an inch long) and requires little care. In the laboratory, these animals live in petri dishes filled with a mix specially formulated for C. elegans health and food (they can use E. coli as a food source). Their life expectancy is about two to three weeks.

The strange but beautiful Aplysia is one of the largest sea hares (about 40 centimeters, or 1 inch, long), making this invertebrate small enough to house easily and large enough to visualize clearly. Eric Kandel, MD, used them to conduct his Nobel Prize winning research on learning and memory. What can these animals learn?  Although they have a very simple nervous system, they need to be aware of whether a repeated stimulus is indicative of danger or not. The changes their neurons undergo during this learning process can help scientists understand the changes that happen in human neurons during learning as well.

Like nematodes and sea hares, the fruit fly is also an invertebrate and is used in research for their small size (about 3-4 millimeters, or .12 of an inch) and large brood size (up to 500).  The fruit fly’s brain is much less complex than that of vertebrates and humans, but many features of its nervous system, such as the eye, share striking similarities to humans. Flies with specific mutant genes have been essential for many critical scientific discoveries, and the fruit fly genome has been fully sequenced. Approximately 60 percent of human genes known to play a role in disease have a counterpart in the fruit fly. In addition to depression, the fruit fly has been useful for research on vision and sleep.

Their transparent eggs make zebrafish excellent candidates for scientists studying developmental neuroscience.  In particular, scientists can watch the nervous system form, which can shed light on how our nervous system develops. Zebrafish also help scientists research fragile X syndrome.

As a group, fish are popular for research; after mice and rats, they are the third most often used protected animal. But zebrafish have one important limitation: Scientists do not yet have a long-term, reliable way to eliminate specific genes, as they do in mice. This limits the number of genetic manipulations scientists can do, even though they have sequenced the zebrafish genome and have identified many well-characterized mutants.

Surprisingly, songbirds are one of the few animals besides humans that learn to vocalize by listening to others. For this reason, songbirds have helped scientists understand how children learn to speak. Although humans and songbirds evolved separately, the motor pathways our brains use to learn vocalization are similar. Interestingly, while male zebra finches begin to sing at puberty, females lack the ability to sing.
Mice and rats are the two most commonly used vertebrate animals in research today. They have the same number of genes as humans do, and most genes are 85 percent similar to their related gene in the human genome. What's more, mice offer scientists the ability to make specific alterations in their genes, allowing for eliminations and additions. Both mice and rats are used for many different types of neuroscience research, including psychiatric disorders, Alzheimer's disease, spinal injury, stroke, and how neurons communicate.

Scientists probing the more complex functions of the brain and nervous system have discovered that dogs have the ability to understand many human words, pigs can learn how mirrors work, and sheep can recognize the faces of other sheep in their flock. Research with mid-sized mammals has resulted in many important findings in cognition and stroke. In addition, research with dogs has led to a successful therapy for vision loss.

Through research with non-human primates, scientists are getting closer to the possibility of helping people who are paralyzed regain motion. Such research, however, accounts for less than one-fourth of one percent of all scientific research on animals, and small monkeys such as marmosets and macaques, are much more commonly used than apes, such as chimpanzees, orangutans, and gorillas. Although humans are evolutionarily closer to apes than they are to monkeys, most neuroscience research can be accomplished using monkeys. Monkeys can be useful for studying complex brain tasks such as decision making. They can also help us make technological advances that can improve the lives of paralyzed people by researching ways in which the brain could communicate with machines to move robotic limbs. But working with non-human primates presents many challenges: They require a lot more living space, care, and personal attention. Additionally, any scientist who works with non-human primates is required to complete additional training courses.

All prescription and non-prescription drugs approved by the Food and Drug Administration (FDA) have been thoroughly tested in both animal models and humans. People participate in clinical trials to test medications before they are approved by the FDA and after they have been used successfully in animals. When participating in clinical trials, humans are protected by a separate division of the Department of Health and Human Services.