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. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=10910