03/16/1995 08:00:00

Biologists Find That Neurotrophic Factors Can Affect Synapses in Adult Rat Brains

PASADENA—Caltech biologists have found that certain proteins in the adult rat brain can strongly enhance the strength of connections between neurons for up to an hour, an effect never before demonstrated in adult brains. This potent, long-lasting physical effect suggests to the scientists that it may play a role in the formation of memories. The study will appear in the March 17 issue of the journal Science.

The proteins, called BDNF and NT-3 for short, belong to a class of proteins called neurotrophic factors, named for their role in nourishing nerve cells during an animal's early development and keeping nerve cells healthy in the adult animal.

Neurotrophic factors are a subject of intense interest right now because of their ability to stimulate damaged neurons to regrow their connections both in a test tube and in animal models. Thus, they present the possibility for reversing such devastating brain disorders as Alzheimer's disease, Parkinson's disease, and Lou Gehrig's disease.

But the Caltech biologists, graduate student Hyejin Kang and Assistant Professor of Biology Erin Schuman, are looking at neurotrophic factors from a slightly different perspective.

"These proteins are usually studied by scientists interested in a developing animal, where they promote structural changes and determine which neurons survive and which will die," Schuman said. "But recently people have realized that these proteins are still active in the adult animal. And we've shown for the first time that they can have an effect on synaptic transmission in the central nervous system."

Kang and Schuman conducted their studies using slices of hippocampus from the brains of young adult rats. The hippocampus is a brain structure known to be important for memory formation, and that is also a part of the limbic system, which is associated with emotion and homeostasis—regulation of the body.

They found that bathing these hippocampus neurons in a solution containing tiny amounts of either of the two neurotrophic factors caused a dramatic and rapid increase in the size of the electric potential of the postsynaptic cells—those cells on the receiving end of signals transmitted from one cell across a synapse to a second cell. The researchers believe this change is due to a direct and persistent strengthening of transmission across synapses. The scientists also looked at the interaction between changes induced by the neurotrophic factors—BDNF and NT-3, and long term potentiation, a different type of long-lasting strengthening of the connections between neurons. They found that neither interfered significantly with the other, which suggests that at least two independent mechanisms exist for boosting synaptic strength.

In fact, the two mechanisms may work together, with the synaptic enhancement reported here contributing to later phases of long term potentiation. The study suggests that one action of neurotrophic factors may be to sharply alter synaptic strength in the period of time before longer-term structural changes occur in the brain.

Or as Schuman put it simply, "these proteins might actually be involved in encoding memories in brains."

Written by John Avery