Neural circuits: Keys to understanding brain damage
If we could visualize what is happening behind the behavior in the brain
of an infant, we would witness a veritable beehive of developmental activity.
At the time of birth, literally hundreds of billions of nerve cells have
been produced in the human brain. These nerve cells must be well nurtured
because we produce no new nerve cells after roughly the time of birth, and
the very same cells need to work for nearly a century.
However, only the simplest circuits, like those in the spinal cord, have
been wired up to keep life processes chugging along just after birth. No
infant jumps rope on the day of birth to celebrate the event!
Ford F. Ebner, professor of psychology and
cell biology and director of the Institute for Developmental Neuroscience
at the John F. Kennedy Center of Peabody College, is a bold explorer of
the brain mechanisms needed for creating or updating information stored
in the brain. These brain changes, often called "neural plasticity,"
provide the underpinnings for perception, learning, memory, cognitive function
and adaptive behavior in general.
"Basically, we understand around a dozen different molecular and cellular
mechanisms that have been proven to be important for changing the properties
of brain circuits," says Ebner, who studies neural activity changes
in animal brain cells in culture dishes, as well as by studying animal behavior
in response to new sensory experiences.
"We are focused on translating the basic information about the brain,
in particular the mechanisms of learning and memory, into better interventions
that are more effective in reversing the impairments produced by brain damage
that cause mental retardation in its extreme form or learning disabilities
in its milder form," Ebner explains.
Ebner is striving to understand the conditions under which impairment or
delays in development occur and how these impairments can be reversed. He
is also pursuing noninvasive insights into the function of human brains
by analyzing normal and abnormal brain wave activity in children.
"The whole language of the brain," Ebner says, "is the way
one nerve cell talks to another. The complexity comes from the fact that
we have 100 billion nerve cells talking to one another through these mechanisms
at the synapses, which are the specific communication points on the surface
of nerve cells. We have to have changes in the synapses before we can have
changes in behavior that we call learning."
Ebner calls himself "a hopeless reductionist." He believes "that
what's called the mind is really the brain. While we are ignorant of the
subtleties of a lot of brain function, in the final analysis it really is
only the brain function and mechanism that produces what we call cognitive
behavior or adaptive behavior."
If something thwarts or interferes with the cellular communication before
or after birth, developmental disabilities or delays can occur. Ebner says
before birth the same small number of cellular and molecular mechanisms
in the brain are always genetically affected and that these faulty mechanisms
can produce developmental delays and disabilities, as opposed to familial
or environmental causes.
"Autism was thought for years to be a disease of professional parents
who didn't give their children enough love and support, but now we know
it's a disease of development that leads to the behaviors that are called
autism. It's mostly a problem of brain function, rather than a social or
familial problem."
Sensory deprivation in infancy, however, is another story.
A newborn's development of neural plasticity requires brain mechanisms that
depend on activity through sensory systems, Ebner notes. Sensory deprivation
through neglect means that these brain mechanisms don't mature and new circuitry
doesn't become functional in the developing brain.
"There are crucial times in development when you must have sensory
activity or certain things don't get turned on -- like the genes necessary
for learning and memory.
"If you don't begin to facilitate certain kinds of learning before
a certain time, it becomes very difficult or impossible to achieve at another
time," Ebner says.
At the Kennedy Center Institute for Developmental Neuroscience, prevention
is seen as the best way to stop abnormalities that occur before birth. However,
prevention requires changing the behavior of pregnant women who may never
be identified as being in need of help.
"In short, prevention is often not possible -- and the problem then
becomes how to reverse the effects of damage to plasticity mechanisms after
they have been impaired in children.
"The answer, we think, is to find therapeutic drugs that enhance the
damaged mechanisms and to use these drugs in conjunction with existing behaviorally-based
interventions. The exact type of behavioral intervention in some cases may
be improved in the future by understanding the rules that regulate brain
plasticity."
As Institute researchers identify the signature of plasticity-impaired brains
in animals, a major goal of the Institute is to translate this knowledge
as quickly as possible to help children with developmental disabilities,
Ebner says. An explosion of new information-gathering techniques in brain
research permit new insights into the functioning of the human brain.
"The next decade promises to bring stunning new insights and greatly
improved interventions to the problems posed by developmental disabilities
and mental retardation," Ebner explains. "Through neuroscience
research in the Kennedy Center, we expect to contribute significantly to
the solution to these problems."
Ebner and his colleagues' research at the Institute for Developmental
Neuroscience has led to several discoveries:
Sensory deprivation caused by administering an "activity block"
affects tiny target structures that hold the receptors, known as dendritic
spines, on nerve cells. Ebner has used a confocal microscope to image the
dendritic spines, structures "we think are essential for learning and
memory," that reside in high numbers on the input side of cells in
the cortex. Changes in effectiveness, occurring at the junctions between
nerve cells, produce learning and memory. The activity block decreases the
number of dendritic spines if given early, and reduces spine function if
the block occurs later in development. Understanding this phenomena may
result in biological arguments stressing that time, duration and intensity
of interventions are critical to optimizing or recovering specific learning
skills in children.
A new way to measure cortical plasticity in rats that provides a sensitive
and quantitative measure of the impact of prenatal toxins on developing
plasticity mechanisms has been discovered.
Simple sensory deprivation just after birth in rats blocks the development
of plasticity after the animals grow up, preventing normal development and
causing learning difficulties. Others have shown repeatedly that enriched
experience produces a larger brain and enhanced learning capacity, and it
can be used to reverse the effects of toxins that in turn improve performance.
Elimination of the brain chemical acetylcholine from the cerebral
cortex of adult rats blocks plasticity completely using their new assay.
Acetylcholine is found to be markedly reduced in the brains of patients
showing the cognitive deficits of Alzheimer's disease. Usually active sensory
experience makes cortical synapses stronger. Acetylcholine depletion blocks
this effect and even allows inactive inputs to become stronger.
Prenatal alcohol exposure has a major impact on two mechanisms known
to be important for normal plasticity: It reduces the "turning on"
of plasticity-related receptors, and it produces abnormal dendritic spines.
Methods borrowed from behavioral pharmacology may be effective in reversing
these deficits.
Abnormal brain mechanisms in an animal model of Down syndrome include
many of the same mechanisms affected by prenatal alcohol exposure, providing
initial support for the theory that all mental retardation, regardless of
cause, may be derived from the degradation of a limited number of brain
mechanisms. This inspires a need to study the best method to reverse the
deficits caused by fetal alcohol effects.
Other things we know about the brain
We are fairly helpless at birth. Less than 1 percent of our brain
circuitry dedicated to receiving sensory information needed for perception
and cognition is functional at that point.
At birth, 100 billion nerve cells in our cerebral cortex set about
wiring incredibly complex circuits (some 5,000 to 10,000 connections to
each nerve cell).
We produce no new nerve cells after roughly the time of birth. These
cells must be nurtured since they must work for the next 80 years or so.
Our infant brain demonstrates on-the-job training; the brain is being
used at the same time it is being assembled.
Through learning mechanisms in the brain, the brain continues to rewire
and change its circuitry throughout our lives.
-Ellen Bourne
-Photo by Billy Kingsley
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