A strategy to understand brains
To understand how the brains of humans and other animals control their behaviour we need to understand their whole nervous system. This is a daunting task, especially in humans where the brain is so complex with billions of nerve cells or neurons. This is clearly not the place to start. What we need is a simple animal with simple behaviour like a very young tadpole. Even the nervous systems of animals like worms and flies have many thousands of neurons making complex connections.
Our research on young frog tadpoles was inspired by the work starting in the 1890s by the American psychologist George Ellet Coghill. He decided that the function of the brain must be studied as a whole if we are to understand how it generates behaviour. After 30 years of research he published a book in 1929 called “Anatomy and the problem of Behaviour” Cambridge University Press, Cambridge.
Coghill’s idea was to choose an easily available simple animal and to correlate the development of its behaviour with the development of the neurons in its nervous system. The animal he chose was the tadpole of the Tiger salamander (Ambystoma tigrinum: Photo thanks to Brian Gratwicke on flickr).
Coghill took motion pictures to define the development of the tadpole’s swimming behaviour in response to touch. It bends into a coil (1 to 4) and then swims off (5 to 10).
His diagram (at the right) shows the nervous system and how the muscle segments contract during swimming. The grey shaded muscle segments are contracting
Coghill then spent many years trying to reveal the anatomy of the neurons in the brain and spinal cord responsible for the swimming response. His book has strikingly simple circuit diagrams of the possible neuronal circuits underlying swimming.
Coghill’s explanation for this circuit was that touching the skin on the left side excites sensory nerve endings among the skin cells. This leads to activity (action potentials) in sensory neurons (red). These sensory neurons excite each other so action potentials reach the brain. In the brain the excitation leads to activity in connecting neurons (black) which pass excitation on to floor plate neurons (x orange). The floor plate neurons carry activity across to the other side where they excite the motor neurons (green). Action potentials then spread from motor neuron to motor neuron towards the tail in this motor path. This excites the muscles to contract in a head to tail sequence. The muscle contractions alternate on each side to produce swimming.
Coghill’s circuits have very few different types of neuron and have inspired later detailed study on how they develop and work. This more recent research started in the 1970s. Unfortunately, it has not confirmed many of Coghill’s pioneering conclusions about the neuronal circuits and the way they work. For example, nobody has been able to find the “Floor plate cells” in his circuit. The anatomical methods available for him to use to define neuron types were just not good enough.
Frog eggs, embryos and tadpoles have been used extensively by developmental biologists to study how an egg develops into a behaving animal with a functioning brain and nervous system. The eggs are large (~ 1mm across) and, as they divide to make an embryo with many cells, the yolk divides too, so each cell has its own supply. This means that parts of the embryo can be removed and will survive and grow on their own. Small pieces can also be transplanted to new positions to see if they influence the development of other tissues (like the lens in the eye). The tissue is remarkably tough and resists bacterial attack.
During the first half of the 20th century, European and American frogs in the genus Rana were used in most studies of development. But, there was a real problem in getting eggs all year round as these frogs only breed in spring. By the 1960s many researchers were using the African Clawed Toad Xenopus laevis (Photo at right) because this breeds in the wild during the rainy season which can occur in different locations in Africa at any time of the year. Breeding could be induced around the year by injecting the hormone Chorionic gonadotrophin. This hormone is produced by pregnant women and excreted in their urine. In the mid-20th century Xenopus colonies were kept in hospitals to use for pregnancy testing. If urine from a woman was injected into a female Xenopus and she laid eggs, then the urine contained chorionic gonadotrophin and the woman was pregnant.
Developmental biologists can therefore use hormone injections to induce Xenopus laevis to breed and provide eggs, embryos and tadpoles at any time of year. Furthermore, Xenopus laevis are entirely aquatic and are easy to keep and look after in aquaria. There is a large community of scientists working on a huge range of questions using different species of Xenopus. (This links to Xenbase.)
Xenopus embryos and tadpoles are used in many studies on the development and operation of the nervous system and brain: how does the nervous system form in the embryo; how do nerve cells or neurons develop from ordinary cells; how do nerve axons make the right connections with other neurons; how do axons find their way from the eye to the correct part of the brain?
The research in our Neurobiology laboratory in the Bristol University was inspired by Coghill’s ideas. We use very young Xenopus laevis tadpoles as a model organism to investigate how the nervous system is constructed and works. When the tadpole hatches, it has behaviour which will allow it to survive. This provides us with what must be one of the simplest vertebrate nervous systems. Other neuroscientists study very young zebrafish for the same reason.
After 24 hours of development the Xenopus embryo has made the beginning of a nervous system. During the next 29 hours it grows into a tadpole and the nervous system and muscles start to function. Then it hatches from the egg and starts to swim. The stages of development have been defined and given numbers:
We use stage 37/38 when the tadpole usually hatches. The behaviour of the hatchling tadpole is simple and described on the tadpole behaviour page.