UT-Houston Scientists Shed Light On How Memories Are Formed

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
Alzheimer1s 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.

Note: The paper by Fan Zhang, Shogo Endo, Leonard J. Cleary,
Arnold Eskin and John H. Byrne (corresponding author) entitled,
Role of Transforming Growth Factor-ß in Long-Term Synaptic
Facilitation in Aplysia, is published in Science, February 28,
1997.