Potential to harness a newly uncovered mechanism of learning

The researchers have shown that the way the brain first captures and encodes a situation or event is quite different from the way it handles subsequent learning of similar events. It is this second stage learning that holds promise if the process can be mimicked therapeutically.

Memories are formed in the part of the brain known as the ‘hippocampus’, a structure the shape of ram’s horns that passes through the right and left hemispheres. The hippocampus is very susceptible to damage through stroke or lack of oxygen, and is critically involved in Alzheimer’s disease.

When a memory is first formed, a small protein involved in synaptic transmission, the ‘NMDA receptor’, is indispensable to the process.

Activation of the NMDA receptor allows calcium to enter a neuron. Calcium permeability enables a chain of molecular reactions that help encode experience and consolidate memory.

Learning theorists have assumed that learning cannot occur without NMDA receptors. The new findings show that NMDA receptors are not essential in ‘second-learning’, when the rules of first-learning are applied to different, yet similar, scenarios. Instead, another class of receptors, also calcium permeable, appear to take up the task.

Over the last 6 years molecular neuroscientist Dr Bryce Vissel, from Sydney’s Garvan Institute of Medical Research, has worked closely with learning theorist Dr Michael Fanselow and electrophysiologist Dr Thomas O’Dell, both from UCLA (University of California Los Angeles), to unravel the two different synaptic mechanisms and their meanings. Their findings are now published online in the journal Plos ONE.

“When we started this research, we knew that the NMDA receptor was implicated in learning and memory, and we decided to see if we could mimic its process through another receptor system,” said Vissel.

“Instead of having to create a new receptor system, we discovered one already in existence – one that was NMDA-independent. This amounted to uncovering a whole new mechanism of learning.”

While stressing that the finding is still in the discovery phase, Dr Michael Fanselow is optimistic about what it could mean for people whose memory formation has been impaired. “The system we’re working with is one that we know is critically involved in Alzheimer’s disease and other kinds of brain deficit memory impairment,” he said.

“This is just the start – we have uncovered a mechanism that contributes to learning and memory, and we now have to figure out what to do with it. When is it important normally? When can we harness it to take over function when the normal mechanisms aren’t working? Can we use it to have some protective effect in conditions like Alzheimer’s disease, where neurons are dying? Can we stimulate these pathways and keep them participating in memories?”

“We can see that we might now have a target for drugs that are different from the standard class of cognitive enhancers. We can also see the possibilities for different styles of training that better activate this newly discovered mechanism.”


Apart from those mentioned in the body of the release, the work involved an international team of other prominent scientists including Stephen Heinemann (Salk Institute); Susumu Tonegawa (MIT); Brian Wiltgen (University of Virginia); Gordon Royle, Andrea Abdipranoto and Nopporn Thangthaeng (Garvan Institute); and Erin Gray, Nate Jacobs and Faysal Saab (UCLA).

The research was made possible by a Silvio O. Conte Center, National Institute of Mental Health Grant P50-MH58880 to S.T. and S.H., the National Science Foundation grant number 0543651 to T.J.O., National Institute of Mental Health grant number MH609197 to T.J.O. and National Institute of Mental Health grant number MH62122 to M.S.F. and a Project Grant under the NSW Spinal Cord Injury & Related Neurological Conditions Research Grants Program, administered by the Office for Science and Medical Research of the State Government of NSW, and by the support of Bill and Laura Gruy, Mr and Mrs Dixon, Walter and Edith Sheldon, Tony and Vivian Howland-Rose, Amadeus Energy Ltd, an oil and gas producer and explorer based in Perth, Western Australia.



The Garvan Institute of Medical Research was founded in 1963.  Initially a research department of St Vincent’s Hospital in Sydney, it is now one of Australia’s largest medical research institutions with nearly 500 scientists, students and support staff. Garvan’s main research programs are: Cancer, Diabetes & Obesity, Immunology and Inflammation, Osteoporosis and Bone Biology, and Neuroscience. The Garvan’s mission is to make significant contributions to medical science that will change the directions of science and medicine and have major impacts on human health. The outcome of Garvan’s discoveries is the development of better methods of diagnosis, treatment, and ultimately, prevention of disease.


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