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Research in my laboratory
Memories are capable of lasting from childhood
throughout life. This extremely long duration indicates that the
brain mechanisms which maintain memory cannot rely solely on physiological
or biochemical mechanisms which are labile but must
involve structural changes. It is generally believed that such
changes occur at synapses, where information is transmitted between
neurons, and we are investigating structural molecules that could
be involved in modifying synaptic morphology (synaptic plasticity).
Our current efforts are focussed on actin, a protein which in
many cells drives the changes in shape that are responsibile for
determining cell morphology. Some years ago my group discovered
that actin in the brain is highly concentrated at dendritic spines
(ref. 1), tiny protusions from dendrites that form the contact
sites at up to 90% of excitatory synapses in areas of the brain,
such as the cerebral cortex and hippocampus, that are involved
in cognitive processing. More recently we have found that the
forms of actin expressed in neurons, b and g actin are specifically
targeted to spines (ref. 2). Does this mean that spines are motile?
To find out we made gene fusion constructs in which actin was
"tagged" with the autofluorescent protein GFP. Using
actinGFP we could follow actin dynamics in a wide variety
of living cells including neurons, and we were able to record
actin dynamics in dendritic spines (ref. 3). This actin based
motility is surprising rapid, with detectable changes in spine
dimensions occuring within seconds. We are currently investigating
the actin dynamics in spines are regulated by synaptic transmission
and we are also exploring the molecular mechanisms by which this
regulation is expressed.
Other interests
Some thoughts about broader aspects of brain function are contained in my essay The Brain in the New Millennium (Acrobat PDF file) which was written for for Brain Awareness Week 1999 and published in Basel's daily newspaper, the Basler Zeitung (in German translation by Ulrich Goetz). Click the link to read my original English text. Thanks to Ulrich Goetz and Martin Hicklin for their support.
Technology
This work has involved us in developing new techniques for imaging molecular dynamics in living cells and in using the latest computerized microsopy equipment. For more details view the videos and images elsewhere on the group's website.
References
1. Matus, A., Ackermann, M., Pehling, G.,
Byers, H. R., and Fujiwara, K. (1982). High actin concentrations
in brain dendritic spines and postsynaptic densities. Proc Natl
Acad Sci U S A 79, 7590-4.
2. Kaech, S., Fischer, M., Doll, T., and Matus, A. (1997). Isoform
specificity in the relationship of actin to dendritic spines.
J Neurosci 17, 9565-72.
3. Fischer, M., Kaech, S., Knutti, D., and Matus, A. (1998). Rapid
actin-based plasticity in dendritic spines. Neuron 20,
847-854.