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Why can’t you sprint a marathon?

20 March 2012

Researchers funded by the Biotechnology and Biological Sciences Research Council (BBSRC) have discovered a new memory mechanism within the nervous system that helps to avoid exhaustion.

The discovery was made while studying how nerve networks control movement in the tadpoles of a frog called Xenopus, a well understood model for studying nerve cells in the spinal cord. This is the first time that such a form of short-term memory has been uncovered in any vertebrate animal.

  Tadpole with inhibited sodium/potassium pumps

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The team from the University of St Andrews publish their findings today (20 March) in the print edition of the journal Current Biology, accompanied by a 'Dispatch' review article highlighting the significance of their findings. Their discovery demonstrates at a fundamental level that even very simple animals have the ability to pace themselves and sheds light on how the brain helps animals regulate activity so as to avoid exhaustion.

Professor Keith Sillar, of the University of St Andrews, who led the research, explains "Many of us know the feeling of tired muscles screaming at us to stop exercising. However, there is growing evidence that our brains contribute to this fatigue and tell us to stop an activity well before the system as a whole is completely exhausted, always holding something in reserve. The need to trade off speed against endurance is important for all animals and we didn't really have any idea how they did it. What we've discovered is a beautifully simple system that essentially allows a tadpole to pace itself."

The first clue that led to their discovery was that following a period of intense swimming the tadpoles subsequently would only swim for short bouts, but after a prolonged resting phase the tadpoles were able to sustain their swimming for significantly longer.

Professor Sillar continues "Put simply, a tadpole can either swim a series of short sprints or more slowly for a long time. The form of simple memory that we've discovered in nerve cells of the spinal cord stops the animal from exhausting itself by trying to run a marathon at sprint speed."

Excitingly, the team found that this new form of memory was being controlled by an incredibly common, but entirely unexpected mechanism.

All of our cells have vast numbers of protein pumps spanning their surface, constantly moving charged particles called ions in and out. One such pump is responsible for transporting positively charged sodium and potassium ions across the cell membrane in order to generate a negative electrical charge in cells compared to their surroundings. It is this mechanism that underpins the electrical firing of neurons in the brains and nervous systems of all advanced organisms. Each cell can have many millions of these pumps and they account for around a third of all energy used in our bodies. However, despite this abundance they have been somewhat overlooked by neuroscientists because they were thought to just run continuously in the background, unresponsive to changes in the animals behaviour or environment.

Contrary to this perceived wisdom the team at St Andrews found that these pumps are involved in an elegant feedback loop that allowed specific nerve cells in the spinal cord to retain a short-term memory of the tadpole's recent activity. The more the spinal networks are active, the harder the pumps work to reduce the activity of the network. This record provides a continuously updated memory of previous activity and stops the tadpole from exhausting itself.

As well as being all pervasive, these pumps are also highly relevant in a number of clinical conditions such as heart arrhythmias and some forms of Parkinson's-like movement disorders. Because this research has shown these pumps play a more sophisticated and adaptable role than previously thought, a number of exciting new avenues of research are now open to scientists.

Dr Hong-Yan Zhang is a postdoctoral researcher at the University of St Andrews. She discovered the mechanism whilst studying the effect of a common drug on the tadpole nervous system. "This was a really exciting discovery that I made quite by chance" said Dr Zhang. "No one had thought to look at these simple pumps as a mechanism for recording memory in the spinal cord because they were just thought to sit in our nerve cells running continuously in the background. Now we have shown that these pumps are far more sophisticated than many people suspected we need to look again for other brain processes that they might be involved in."

Professor Douglas Kell, BBSRC Chief Executive said "This is a very interesting discovery and shows how even aspects of biology that we think are well understood can throw up surprises. This underlines the need for us constantly to push at the boundaries of our understanding of fundamental biology because only with more knowledge will we be able to fulfil the potential of biology to improve our lives and grow our economy."

The paper on which this story is based, Short-Term Memory of Motor Network Performance via Activity-Dependent Potentiation of Na+/K+ Pump Function, by Zhang and Sillar is available here:  www.cell.com/current-biology/abstract/S0960-9822(12)00088-7 (subscription may be required)

A dispatch review of the article by Dr John Simmers is available here:  www.sciencedirect.com/science/article/pii/S0960982212001376 (subscription may be required)

ENDS

About BBSRC

BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.

Funded by Government, and with an annual budget of around £445M, we support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.

For more information about BBSRC, our science and our impact see: www.bbsrc.ac.uk .
For more information about BBSRC strategically funded institutes see: www.bbsrc.ac.uk/institutes .