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

             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

                                       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

                                       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

                                       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

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