Download When you learn something new, the connections between your

The neurobiology of
Learning and Memory
and the incredible plastic brain
When you learn something new, the connections
between your brain cell change in dynamic ways. Because
new experiences can cause nerve cells, or neurons, and their
connections, called synapses, to be molded into a different
shape with better properties, we say the brain is plastic, or
has plasticity. This plasticity of the brain enables us to learn
and form new memories.
We use many different techniques to help us study
brain plasticity during learning and memory. We use rats
and mice to study behavior. We use compound light
microscopes to study changes in neurons. We use an
electron microscope to study changes in synapses. We use
many molecular and biochemical techniques to study
proteins, RNA, and other molecules in neurons and
synapses. These tools help us study the links between
behavior and changes in the brain and how different types
of changes in the brain interact with each other.
We have discovered several important things in the
field of the cellular and molecular basis of learning
memory. We have observed that when rats live in a
complex environment with many opportunities for new
experiences, their neurons form more synapses than
neurons of rats who live in simple cages with little
opportunity for new experience. Also, rats who have
learned how to navigate a complex acrobatic obstacle
course have more synapses per neuron compared to rats
who engage in simple exercise such as running in a running
wheel.
Many of our investigations of learning and memory
are focused at the molecular level. We have discovered that
proteins are manufactured at synapses in response to
specific types of synaptic activity. Every day we learn more
about how the special proteins and other molecules found
at synapses are involved in learning and memory.
Each project described in this brochure relates to the
molecular and cellular understanding of how the brain
accomplishes the complex tasks of information processing
and storage we call learning and memory.
The neurobiology of
Fragile X
mental retardation syndrome
When the brain lacks the tools to learn, mental
retardation develops. People affected with Fragile X
Syndrome lack the ability to manufacture one protein. The
absence of this protein, called FMRP (Fragile X Mental
Retardation Protein), affects their ability to learn. We have
discovered that FMRP is made at synapses.
Genetic engineering technology allows us to study a
mouse model of Fragile X syndrome. We have shown that
the mouse model has abnormal neuronal spines which look
very much like those of human Fragile X brains. Now we
are investigating deeper into the Fragile X mouse brain. We
are studying the biochemical processes in which FMRP
plays a role. One recent discovery is that FMRP at synapses
is required for the manufacture of other proteins that
manufacture proteins. This is an important discovery that
may one day provide a way to bypass the absence of FMRP.
Autopsies of brains from human Fragile X patients
show that their neurons look very different from those of
unaffected people. A neuron has arm-like projections with
many branches. The smallest branches are called spines and
they make synapses with other neurons. The spines of
neurons in a Fragile X brain have shapes that resemble
immature, developing spines instead of the mature spines
we see in a normal brain. We are studying how the lack of
FMRP might disrupt the normal shape of neurons.
Fetal Alcohol Syndrome
a possibility for therapeutic intervention
Alcohol consumption during pregnancy can lead to
serious brain damage in the developing fetus. The most
severe form, fetal alcohol syndrome, exhibits distinct
physical abnormalities (e.g., very particular facial features),
growth and development delay, mental retardation (with a
wide spectrum from total withdrawal from reality to slight
but significant deficits in learning and memory). For the
developing fetal brain the effect of alcohol is disastrous:
brain size may decrease by 20-30% (depending on the dose
of alcohol that mother (and baby) consumed) because of the
resulting death of neurons. A less severe but still
debilitating syndrome, alcohol-related neurodevelopmental
disorder, exhibits no facial abnormalities but involves loss
of neurons, growth retardation, mild to severe mental
retardation, and psychosocial dysfunction. We are studying
rehabilitative intervention in this disorder, using an animal
model.
It is well known that all neurons in most areas of the
nervous system are born early in development and can
never be replaced once they die, unlike other cells in the
body. What can be done, using our knowledge of brain
plasticity, is to try to modify the remaining neurons (the
survivors) so that they compensate, at least to some extent,
for the loss of some of their neighbors. In our animal model
of drinking during the third trimester of pregnancy, rats
that receive alcohol are initially very clumsy on the complex
acrobatic obstacle course that we use as a rehabilitative
procedure, including parallel bars and a rope ladder. After
a period of such training their performance improves so
dramatically that they are no longer different from normal
rats. We have discovered that this improvement in
performance involves plastic changes in brain cells, in
which they add extra synaptic connections. Investigators at
other institutions have begun human intervention trials,
based in part on our work.
The neurobiology of
Major Depression
a brain disorder
Depression is a common psychiatric illness that is
frequently debilitating and often life-threatening. It is the
number one cause of disability and death worldwide.
Medical research has indicated that humans become
vulnerable to depression through a complex interaction of
genetics, early experience, and the present environment.
We are studying how different kinds of experience can
affect the emergence of depressive and anxious behaviors in
rodents. We are also looking for brain changes that are
associated with animal models of depression and how these
changes can be influenced by experience.
The neuroanatomy of
Schizophrenia
a brain disorder
Schizophrenia affects about 1% of the population
worldwide, and although sometimes devastating, it is
generally treatable. These people often have psychotic
symptoms (e.g., hallucinations, delusions), as well as
difficulties with concentration and memory.
Research suggests that the psychotic symptoms
and cognitive deficits may involve anatomical brain
changes at the cellular level. In order to learn more about
this brain disorder, we are working with colleagues in
Russia to compare the microscopic anatomy of brains
from schizophrenic and normal people. We will
summarize research in the causes of schizophrenia, how
it affects the brain and its treatment.
Autism
a neurodevelopmental disorder
Autism is a rare brain disorder that can have a
devastating impact on patients and their families. In the
severe form of autism, children lose their language
ability and social skills, and they often do repetitive, odd
behaviors. Research has indicated that genetics and
possibly prenatal brain damage may cause these
symptoms. Autism was widely believed to be
untreatable until the 1990’s, when research showed that
early intense therapy could substantially help many
autistic children. We are working with some other
scientists to study the neuropathology of autistic
individuals who generously donated their brains to
research. In parallel, we are studying an animal model of
autism, using subtle prenatal brain damage and then
seeing how that affects behavior and neural plasticity
later.
Animal Research and Welfare
without lab animals,
where would we be?
There is not a person alive today who has not
somehow benefited from the advances in health care that
were made possible by medical research using
laboratory animals. However, most of us take for
granted the availability of antibiotics, drugs for
treatment of a wide variety of diseases such as
hypertension, high cholesterol, diabetes, AIDS, mental
illness, vaccines against diseases that no longer threaten
our health, and cancer therapies that have cured or
lengthened lives. Today, open-heart surgery,
neurosurgery, thoracic surgery, and organ
transplantation are routinely done. All of these lifesaving surgical procedures were made possible from
knowledge gained from using animal models in
scientific research.
Yet in spite of this remarkable progress in medical
science, there is still much work to be done. There is a
long list of diseases for which there is still no prevention,
treatment, or cure. These include Alzheimer’s disease,
Parkinson’s disease, Fragile X Mental Retardation, cystic
fibrosis, muscular dystrophy, cancer, and AIDS. The use
of animals as models in scientific research along with
non-animal technologies will continue to be essential to
our quality of life.
Adapted from ”Understanding the Use of Animals in Biomedical
Research,” Foundation for Biomedical Research 1992.
Contact Information:
About projects 1-3:
Kathy Bates
Beckman Institute
University of Illinois at Urbana-Champaign
405 N. Mathews Ave.
Urbana, IL 61801
(217) 333-4472
[email protected]
http://soma.npa.uiuc.edu/labs/greenough/home.html
About projects 4-6:
James E. Black, Ph.D., M.D..
Beckman Institute
University of Illinois at Urbana-Champaign
Psychiatry Department
405 N. Mathews Ave.
Urbana, IL 61801
(217) 244-9018
[email protected]
Research funding:
- FRAXA Research Foundation
- Kiwanis Nervous System Research Foundation
- McDonnell Foundation
- National Institutes of Health (NIH)
- National Association for Research on Schizophrenia and
Depression (NARSAD)
- Cure Autism Now Foundation
Your Brain!
What’s going on in there?
Here is a quick look at some of the
brain research going on at the
University of Illinois’ Beckman
Institute...
Research conducted by
William T. Greenough, Ph.D.
James E. Black, M.D., Ph.D.
Ivan Jeanne Weiler, Ph.D.
Anna Y. Klintsova, Ph.D.
Take a Look
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