X-Message-Number: 13082
Date: Thu, 13 Jan 2000 16:21:51 -0500
From: Jan Coetzee <>
Subject: Controlling the neuron crowd

EMBARGOED FOR RELEASE: 13 JANUARY 2000 AT
    14:00 ET US

    Contact: Jeffrey J. Sussman, Asst. V.P. Communications
    
    212-895-7951
    Weizmann Institute

REHOVOT, Israel - Despite more than a century of research on
inhibitory neurons, very little is known on how this small population
(10-20% of brain neurons) exerts its controlling effect on the brain.
Pivotal for normal brain development, learning, and memory, it is not
surprising that inhibitory neurons are involved in most neurological
disorders. A recent study at the Weizmann Institute of Science,
published
in
the January 2000 issue of Science, reveals key principles underlying the

design and function of this inhibitory system.
      By repressing the level of activity in neighboring neurons,
inhibitory
neurons (I-neurons) preventthe brain from quickly spinning out of
control
into hyper-excited states or full-blown epilepsy. One of the problems
that
children with autism and attention deficit hyperactivity disorders
(ADHD)
have is I-neuron malfunction: their inhibitory system does not
effectively
suppress unwanted information, impeding their ability to make choices.
I-neuron malfunction is involved in memory disorders (such as
Alzheimer's
disease), neural trauma, and addictions. It also plays a role in a wide
range of psychiatric disorders, such as depression, obsessive compulsive

disorders, and schizophrenia.
      In the past, researchers basically thought that I-neurons just
sprayed
an inhibitory neurotransmitter called GABA onto their neighbors. But
this
did not explain how they inhibited the right neurons at exactly the
right
time and to the right degree. The new study carried out in the
laboratory
of
Prof. Henry Markram of the Weizmann Institute's Neurobiology Department
shows how they achieve this.

      Controlling the neuron crowd
      The research team found new types of I-neurons, revealing that
this
tiny population is several times more diverse than previously thought.
Further, using new methods that they developed, the researchers
succeeded
in
recording directly how individual inhibitory neurons control their
neighbors. They found that I-neurons build complex synapses
(connections)
onto their target neurons. The synapses selectively filter inhibitory
messages, enabling I-neurons to shut down the activity in neighbors as
required.
      These synapses act as fast-switching "if-then" filtering gates
that
allow inhibition to be applied only at the exact millisecond and to the
right degree. Each I-neuron establishes complex if-then gates onto
thousands
of neighboring neurons and is therefore "in charge" of controlling their

activity. The gates allow I-neurons to rapidly switch their focus onto
any
one neuron that they are connected to. This ingenious design principle
is
what enables the small group of I-neurons to exert such a sophisticated
effect, simultaneously "giving personal attention" to the activity of
each
of the neurons to which they are connected.

      At the negotiating table
      The researchers showed that a "discussion" between I-neurons and
target neurons is involved in deciding which type of if-then gate should
be
set up to filter the inhibitory message. This decision-making process
could
allow each neuron in the brain to be inhibited in a potentially unique
way.
Dubbed the "interaction principle," this process generates maximal
diversity
of if-then gates, allowing more complex and finer control over large
numbers
of neurons.

      A potential brain-mapping tool
      The researchers went on to reveal a remarkable ability of
I-neurons:
they can sense neurons that share the same functions in the brain.
I-neurons
"select" groups of target neurons to construct the same type of if-then
gates, possibly enabling the I-neurons to control groups of neurons
collectively.
      It also means that I-neurons can "smell-out" neurons in the brain
that
collaborate in the most elementary functions even if they seem different
in
almost every other way (i.e., they can identify neurons descended from
the
same "ancestors"). "I-neurons can trace family trees of neurons. In
other
words, they could help us to work out how neurons are related to each
other.
      This could one day enable us to map the functional aspect of the
brain
according to the genealogy of neurons - an organizing principle that we
never dreamt possible," says Markram. The researchers believe that the
ability to detect functionally related groups in the brain, called "the
homogeneity principle," results from common signal molecules released by

target cells. I-neurons may use the signal molecules to determine what
kind
of if-then gates to build. Future research designed to identify the
nature
of these molecules could yield a potent tool for mapping the functional
structure of the brain.
                   ###
      This research was funded by the Human Frontier Science Program
Organization, the Israel Ministry of Science, the Israel Science
Foundation,
the US Navy, Minna James Heineman Stiftung, the Abramson Family
Foundation
and the Nella and Leon Benoziyo Center for Neurosciences. A member of
the
Weizmann Institute's Neurobiology Department, Prof. Henry Markram holds
the
Joseph D. Shane Career Development Chair.
* * *

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