X-Message-Number: 10910
Date: Fri, 11 Dec 1998 22:20:39 -0500
From: Jan Coetzee <>
Subject: dendritic spines
Spiny Relationships
by Clare Thompson
Tiny spiny outgrowths on the
surface of neuronal dendrites may
hold the key to the architecture of
the human brain and the underlying
basis of memory and learning. At
the Society for Neuroscience
meeting (10th Nov) Kristen Harris
from Harvard Medical School
headed a symposium aimed at
addressing the century-old
question of what are these
dendritic spines for, and what
regulates their function?
The outgrowths, otherwise
known as dendritic spines,
have either been ignored by,
or have confounded
neuroscientists ever since
Ramon Y Cajal
demonstrated the extent of
dendritic branching. In the
1950's, the electron
microscope made it possible
to verify the existence of
many synapses on the
dendritic branch and
dendritic spines of neurons.
Now, however, it seems
clear that dendritic spines
are the main target for
excitatory synaptic inputs,
and for making important
synaptic connections
between the dendrite and
the axon, but there are still
many unanswered questions
as to their actual role and
several conundrums that
have a wider bearing. The
dendritic spines for instance
will elongate in the
presence of estradiol or
caffeine, and may provide a
mechanism to many of the
recent clinical trials showing
that hormone replacement
therapy appears to be
protective against
Alzheimer's disease.
Kristen Harris believes the
answer to the question of
how do the spines mature in
the hippocampus lies via the
techniques of serial electron
and con-focal microscopy.
The studies showed that
dendritic spines arise from
shaft synapses during
development, are stable by
2 hours after long-term
potentiation in adult
hippocampal slices.
In addition, Kristen's team
discovered that many new
spines are formed when the
synaptic transmission is
blocked in the adult
hippocampal slices,
indicating a highly plastic
nature.
Stephen Smith from Stanford
Medical School was much
more concerned about the
dendritic motility during
synaptogenesis. Just exactly
how did this small spiny
dendritic thing manage to
link up with its desired
axonal partner? According to
him, the real 'star of the
show' was the spine's
younger
sister - the dendrite
filopodium. Renowned for its
highly motile properties, the
filopodia may be responsible
for seeking out the axon.
Again there are more
questions than answers, but
that does not seem to
bother Steve, who is happy
to spend time in a personal
oddessey to discover the
whole truth of the
spine-filopodia-axon
relationship.
As his real time video so
vividly demonstrated,
Stephen has discovered that
when glutamate is added to
cultured neonatal
hippocampal cells, filopodia
will grow outwards at 2
microns per second. Such
growth, he says, is typical
of the early stages in
synapse development but is
not often found in the
mature brain. When the
synapse has formed, the
filopodia are no-where to be
seen, yet the dendritic
spines become steadily
more apparent. Smith
believes that this could be
because the highly motile
filopodia are the first stage
in spine development.
He believes the contact
between the dendrite and
the axon is initiated by the
filopodia, which then
entwine themselves around
the axon. This according to
Stephen Smith, is more of a
push and pull relationship
rather than a typical
neighborly cell-cell contact.
Once the filopodia and the
axon join, the filopodia may
retract back towards the
dendrite. Akin, says Smith,
to an Archer drawing back
the string of a bow before
he shoots his arrow. If the
filopodia only partially
retracts, it will result in a
spine synapse. If it retracts
the full distance, then the
resulting structure is a shaft
synapse.
Whatever the mechanism,
the dendritic spine has
managed to hide its true
function for over 100 years.
It does not appear to want
to give up its secrets so
lightly.
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