December 3, 2004

Cornell Scientists Look at Memory

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Scientists from the Weill Cornell Medical College and the National Institutes of Health have teamed up to solve the mystery of how intricately regulated memory is in the human mind. In the Oct. 15 issue of Science, Dr. Barbara Hempstead, co-chief of the Division of Hematology/Oncology of Medicine at Weill Cornell Medical College in New York City, and Dr. Bai Lu of the NIH, explained how they discovered that certain neurons crucial for memory formation regularly produce and release a protein called brain-derived neurotrophic factor (BDNF).

After achieving success with more than a decade of research into how a synapse can become more or less efficient and how a brief increase in synapse efficiency can allow a short-term memory become a long-term one, in their latest paper, Hempstead and Lu have shown how BDNF plays an imperative role in making synapses more efficient.

Human long-term memory is a long and complex process that can only occur when synapses are made to be more efficient. The brain learns by holding information in networks of neurons connected by these efficient synapses and remembers by activating the necessary networks needed in order to recall a memory.

Forgetfulness or forgetting information in general is like what happens when synapses become less efficient, so the network storing the information exists in a less functional state and is undistinguishable from the billions of other networks that exist between the neurons and synapses in the brain.

Although Eric Kandel of Columbia University identified the enzyme tissue plasminogen activator (tPA) that must be present for a long-term memory to form, no researcher until now has understood what that protein’s role is in brain function. tPA, an enzyme widely used for clot-busting, posed many questions as to why it would function in human memory.

At the NIH, Lu studied the effect of certain proteins calledneurotrophins on synaptic efficacy. In his studies, he has shown that BDNF (a neurotrophin) plays a crucial role in making synapses more efficient.

Hempstead, an attending physician at NewYork- Presbyterian Hospital/Weill Cornell, has also studied neurotrophins. Like many proteins, neurotrophins are made in large “pro-form,” which is then cut by enzymes into smaller pieces. Before Hempstead’s research, scientists believed that only the smaller neurotrophins were biologically active. However, Hempstead has shown that the pro-forms are also biologically active and that the cleavage of neurotrophins functions like a switch where outcomes vary according to whether the pro-forms are cleaved or not.

In their latest collaborative efforts, Hempstead and Lu have discovered that certain neurons which are crucial to memory formation regularly make and release pro-BDNF. The cleaved pro-BDNF to BDNF in conjunction with tPA, serve as an amplification cascade to intensify synaptic activity, and thus long-term memory is locked into place.

Other authors on the paper include many scientists from the NIH and collaborators from Weill Cornell Medical College.

By identifying the key events and proteins that are involved in long term memory, the findings of Lu and Hempstead may help in the development of drugs to aid memory disorders and forgetfulness.

Lu is a Senior Investigator in the Section on Neural Development and Plasticity at the NIH and Hempstead is also the O. Wayne Isom Professor of Medicine at Weill Cornell.

Archived article by STEPHANIE WICKHAM
Sun Staff Writer