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Building the Best Brain: How Brain Cell Connections Get Cemented
Early in Life
Sep. 20, 2013 When we're born, our brains aren't
very organized. Every brain cell talks to lots of other
nearby cells, sending and receiving signals across
connections called synapses.
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But as we grow and learn, things get a

bit more stable. The brain pathways
that will serve us our whole lives start to
organize, and less-active, inefficient
synapses shut down.
But why and how does this happen?
And what happens when it doesn't go
normally? New research from the
University of Michigan Medical School
may help explain.

In a new paper in Nature Neuroscience,

a team of U-M neuroscientists reports important findings about
how brain cells called neurons keep their most active
connections with other cells, while letting other synapses lapse.
Specifically, they show that SIRP alpha, a protein found on the
surface of various cells throughout the body, appears to play a
key role in the process of cementing the most active synaptic
connections between brain cells. The research, done in mouse
brains, was funded by the National Institutes of Health and
several foundations.
The findings boost understanding of basic brain development -and may aid research on conditions like autism, schizophrenia,
epilepsy and intellectual disability, all of which have some basis
in abnormal synapse function.

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Two neighboring brain cells "talk" to one another

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by sending signals across a gap called a synapse. and Google +1:
The more active the synapse during development,
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the other, and helps stabilize the synapse for the
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Chemical synapse

"For the brain to be really functional, we need to keep the most

active and most efficient connections," says senior author
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Hisashi Umemori, M.D., Ph.D., a research assistant professor
at U-M's Molecular and Behavioral Neuroscience Institute and
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assistant professor of biological chemistry in the Medical
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School. "So, during development it's crucial to establish efficient
connections, and to eliminate inactive ones. We have identified a
key molecular mechanism that the brain uses to stabilize and
maturate the most active connections."

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Umemori says the new findings on SIRP alpha grew directly out
of previous work on competition between neurons, which
enables the most active ones to become part of pathways and
circuits.
The team suspected that there must be some sort of signal
between the two cells on either side of each synapse -something that causes the most active synapses to stabilize. So
they set out to find out what it was.
SIRP-rise findings
The group had previously shown that SIRP-alpha was involved
in some way in a neuron's ability to form a presynaptic nerve
terminal -- an extension of the cell that reaches out toward a
neighboring cell, and can send the chemical signals that brain
cells use to talk to one another.

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SIRP-alpha is also already known to serve an important function

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in the rest of the body -- essentially, helping normal cells tell the
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Fewer Synapses, More
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Through a range of experiments, they showed that when a brain
Molecular Glue Wires the
cell receives signals from a neighboring cell across a synapse, it
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actually releases SIRP-alpha into the space between the cells.
Researchers have found that a single molecule not
It does this through the action of molecules inside the cell -only connects brain cells but also changes how we
called CaMK and MMP -- that act like molecular scissors,
learn. The findings may help researchers discover
cutting a SIRP-alpha protein in half so that it can float freely
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> read more
The part of the SIRP-alpha protein that floats into the synapse
"gap" latches on to a receptor on the other side, called a CD47 Better Way Developed to See Molecules at
Work in Living Brain Cells (Oct. 12, 2010) By
receptor. This binding, in turn, appears to tell the cell that the
creating a better way to see molecules at work in
signal it sent earlier was indeed received -- and that the

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01/10/2013 08:48

Building the best brain: How brain cell connections get cemented early i...

2 of 2

synapse is a good one. So, the cell brings more chemical

signaling molecules down that way, and releases them into the
synapse.
As more and more nerve messages travel between the
"sending" and "receiving" cells on either side of that synapse,
more SIRP-alpha gets cleaved, released into the synapse, and
bound to CD47.

http://www.sciencedaily.com/releases/2013/09/130920094219.htm?ut...

living brain cells, researchers are helping elucidate

molecular mechanisms of synapse formation.
These studies could also help further ... > read
more

Forgotten But Not Gone: How The

Brain Re-Learns (Nov. 22, 2008)
Thanks to our ability to learn and to
remember, we can perform tasks
The researchers believe this repeated process is what helps the that other living things can not even dream of.
cells determine which synapses to keep -- and which to let
However, we are only just beginning to get the gist
wither.
of what really goes on in the ... > read more
Umemori says the team next wants to look at what happens
when SIRP-alpha doesn't get cleaved as it should -- and at
what's happening in cells when a synapse gets eliminated.
"This step of shedding SIRP-alpha must be critical to developing
a functional neural network," he says. "And if it's not done well,
disease or disorders may result. Perhaps we can use this
knowledge to treat diseases caused by defects in synapse
formation."
He notes that the gene for the CD47 receptor is found in the
same general area of our DNA as several genes that are
suspected to be involved in schizophrenia.

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The above story is based on materials provided by

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Note: Materials may be edited for content and length. For
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1. Anna B Toth, Akiko Terauchi, Lily Y Zhang, Erin M JohnsonVenkatesh, David J Larsen, Michael A Sutton, Hisashi
Umemori. Synapse maturation by activity-dependent
ectodomain shedding of SIRP. Nature Neuroscience,
2013; DOI: 10.1038/nn.3516

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