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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
Science 15 July 2005: 446-451. Link
to Article Supporting Online Material.
Abstract:
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 α7 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.
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Communication between neurons in the brain occurs at synapses -- specialized
points of contact where one neuron sends a chemical signal to its neighbor.
This image shows a realistic computer simulation of neurotransmission
in a
chick ciliary ganglion synapse. The 3D structure of the synapse was obtained
from nano-scale resolution electron microscope tomography of chick brain
tissue. The function of this synaptic structure was then simulated in
a
computer using MCell -- software for simulation of cellular microphysiology.
Yellow spheres represent synaptic vesicles (~50 nm in diameter) containing
~10000 acetylcholine (ACh) neurotransmitter molecules. Green ovoids represent
ACh molecules released from three separate vesicles to signal a neighboring
neuron whose post-synaptic membrane is shown in light blue. After release,
ACh
molecules move by the process of diffusion and bind to two types of
ion-channels called alpha-7- and alpha-3*- nicotinic acetylcholine receptors
(nAChRs), shown as translucent blue diamonds and red spheres, respectively.
The ion-channels are protein molecules embedded in the post-synaptic membrane.
Opacity of nAChR color corresponds to level of ACh binding and subsequent
nAChR
activation (fully opaque = fully activated and open ion-channel). Three
separate vesicle releases are shown here at different points in time after
release -- 10 microseconds for the upper left release site, 100 microseconds
for the upper right release site, and 200 microseconds for the lower release
site.
Download a hi-res version of this image (1200x1554, 492KB) here. |
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