Researchers led by John H. Byrne, Ph.D., professor and chairman, department of neurobiology and anatomy, UT-Houston Medical School, set out to explore the phenomenon by which learning strengthens the connections between neurons, an event observed when long-term memory is formed. Using an experimental system based on the defensive withdrawal reflex of the snail, Aplysia, the team tested the hypothesis that growth factor TGF-Beta, which is known to be important in early development of the nervous system, also plays a key role in long-term memory. TGF-Beta was introduced and was found to produce stronger electrical nerve cell connections when measured 24 hours and 48 hours later. These persistent changes are similar to those recorded in animals whose enhanced withdrawal response is triggered by behavioral training. TGF-Beta's effects were limited to long-term memory: testing soon after its application failed to show a significant change.
Eric R. Kandel, M.D., senior investigator at the Howard Hughes Medical Institute, Columbia University, believes this work represents a major advance in understanding of the molecular mechanisms involved in memory. He comments, "In an elegant series of experiments, the Houston team have shown that TGF-Beta can induce long-term facilitation in the sensory motor neurons of Aplysia. Moreover, the response was selectively blocked by inhibitors of TGF-Beta. Here is the first direct evidence that the growth of new synaptic connections between nerve cells might involve a class of neurotrophic growth factors important in development and therefore provide another important bridge between developmental processes on the one hand and memory storage on the other. These studies also provide some of the first insights into the molecules that are important in establishing the structural changes that occur with long-term memory.
The Science paper authored by F. Zhang et al. adds to the body of work aiming to explain the complex chain of events linking learning, memory, proteins and genes. Byrne points out that only recently have scientists demonstrated that there are common factors in the molecular mechanisms of learning and memory and those which determine the "patterning" and connectivity of the nervous system. He explains, "Physical development of the nervous system begins in the embryo and continues until after birth. While some neuroanatomists working in the late 19th century suspected that learning involved changes to the structure of the nervous system, the prevailing belief was that the two were totally separate. We now know that not only does learning involve physical changes in the way cells communicate, but that those changes utilize mechanisms common to the actual formation of the nervous system.
"The discovery that transforming growth factor TGF-Beta, earlier shown to play an important developmental role, can also simulate an effect normally acquired only after learning, opens the door to the possibility of developing new therapies for those who suffer from stroke, brain injuries or Alzheimer's disease." This research, funded by the National Institutes of Health and conducted primarily at UT-Houston Health Science Center, also involved Dr. Arnold Eskin of the department of biochemical and biophysical sciences at the University of Houston, a long-standing collaborator of Byrne. In addition to chairing the Medical School department, Byrne is director of the UT-Houston Neuroscience Research Center, an organization representing over 200 faculty members, scientists and clinicians engaged in diverse, multidisciplinary research in the neurobehavioral sciences.
Notes to Editors: The paper by Fan Zhang, Shogo Endo, Leonard J. Cleary, Arnold Eskin and John H. Byrne (corresponding author) entitled, Role of Transforming Growth Factor-Beta in Long-Term Synaptic Facilitation in Aplysia, is published in Science, February 28, 1997.
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