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Science 15 July 2005:
Vol. 309. no. 5733, pp. 446 - 451
DOI: 10.1126/science.1108239
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Research Articles

Evidence for Ectopic Neurotransmission at a Neuronal Synapse

Jay S. Coggan,1,3* Thomas M. Bartol,1,8* Eduardo Esquenazi,3,5 Joel R. Stiles,6,7 Stephan Lamont,3 Maryann E. Martone,3,4 Darwin K. Berg,5 Mark H. Ellisman,3,4 Terrence J. Sejnowski1,2,5,8{dagger}

Neurotransmitter release is well known to occur at specialized synaptic regions that include presynaptic active zones and postsynaptic densities. At cholinergic synapses in the chick ciliary ganglion, however, membrane formations and physiological measurements suggest that release distant from postsynaptic densities can activate the predominantly extrasynaptic {alpha}7 nicotinic receptor subtype. We explored such ectopic neurotransmission with a novel model synapse that combines Monte Carlo simulations with high-resolution serial electron microscopic tomography. Simulated synaptic activity is consistent with experimental recordings of miniature excitatory postsynaptic currents only when ectopic transmission is included in the model, broadening the possibilities for mechanisms of neuronal communication.

1 Computational Neurobiology Laboratory, The Salk Institute, La Jolla, CA 92037, USA.
2 Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD, 20815, USA.
3 National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA 92093, USA.
4 Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
5 Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
6 Pittsburgh Supercomputing Center, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
7 Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
8 Center for Theoretical Biological Physics, University of California, San Diego, La Jolla, CA, 92093–0374, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed: terry{at}salk.edu

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