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WORKSHOP ON:
CENTRAL PROBLEMS IN SINGLE CELL COMPUTATION
16-18 September 2002
By invitation only
Venue
B10 Seminar Room, Alexandra House, 17 Queen Square, London, WC1N 3AR
Calcium-based coincidence detection in
cerebellar Purkinje neurons |
Samuel S.-H. Wang, Princeton
University, USA |
In cerebellar Purkinje neurons, the
co-activation of parallel fiber synaptic inputs with the climbing fiber input leads to
physiological effects on both short (<1 second) and long (up to days) time scales. On a
short, subsecond time scale, synaptic co-activation of parallel and climbing fibers causes
large calcium signals that arise from a combination of voltage-gated entry and release
from internal stores. When the number of activated parallel fibers is small, these signals
can be restricted to single dendritic spines. These spine calcium signals are necessary
for the induction of long-term depression (LTD) at the parallel fiber synapse, a
phenomenon that can last up to days and may play a key role in several forms of motor
learning. These calcium signals rely not on NMDA receptors (a common suspect in such
matters), but on metabotropic glutamate receptors that couple to production of the second
messenger IP3. My laboratory is interested in how IP3-mediated calcium release might
perform coincidence detection, and how this mechanism translates into a synaptic learning
rule for LTD. In our current working model, calcium signal dynamics are determined by
interactions among IP3 production, calcium buffering proteins, and IP3 receptors. We
furthermore expect that calcium signals can predict both when LTD will occur and how far
it can spread. For instance, spine calcium signals are largest when the parallel fibers
begin firing up to 100 msec before the climbing fiber fires; this condition also leads to
reliable LTD. We are testing our ideas using uncaging and multiphoton imaging. |
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