Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
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
Abstract:
Neurotransmitter release is well known to occur at specializedsynaptic regions that include presynaptic active zones and postsynapticdensities. At cholinergic synapses in the chick ciliary ganglion,however, membrane formations and physiological measurementssuggest that release distant from postsynaptic densities canactivate the predominantly extrasynaptic 7 nicotinic receptorsubtype. We explored such ectopic neurotransmission with a novelmodel synapse that combines Monte Carlo simulations with high-resolutionserial electron microscopic tomography. Simulated synaptic activityis consistent with experimental recordings of miniature excitatorypostsynaptic currents only when ectopic transmission is includedin the model, broadening the possibilities for mechanisms ofneuronal 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.
To whom correspondence should be addressed: terry{at}salk.edu
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Vladan Lucic and Wolfgang Baumeister (15 July 2005) Science309 (5733), 387.
[DOI: 10.1126/science.1115632] |Summary »|Full Text »|PDF »
Short-term plasticity constrains spatial organization of a hippocampal presynaptic terminal.
S. Nadkarni, T. M. Bartol, C. F. Stevens, T. J. Sejnowski, and H. Levine (2012)
PNAS
109, 14657-14662
|Abstract »|Full Text »|PDF »
Syntaxin1A Lateral Diffusion Reveals Transient and Local SNARE Interactions.
C. Ribrault, J. Reingruber, M. Petkovic, T. Galli, N. E. Ziv, D. Holcman, and A. Triller (2011)
J. Neurosci.
31, 17590-17602
|Abstract »|Full Text »|PDF »
Dendritic SNAREs add a new twist to the old neuron theory.
Spontaneous Neurotransmission: An Independent Pathway for Neuronal Signaling?.
E. T. Kavalali, C. Chung, M. Khvotchev, J. Leitz, E. Nosyreva, J. Raingo, and D. M. O. Ramirez (2011)
Physiology
26, 45-53
|Abstract »|Full Text »|PDF »
Fast synaptic transmission in the goldfish CNS mediated by multiple nicotinic receptors.
C. L. Grove, T. M. Szabo, J. M. McIntosh, S. C. Do, R. F. Waldeck, and D. S. Faber (2011)
J. Physiol.
589, 575-595
|Abstract »|Full Text »|PDF »
Designing communicating colonies of biomimetic microcapsules.
G. V. Kolmakov, V. V. Yashin, S. P. Levitan, and A. C. Balazs (2010)
PNAS
107, 12417-12422
|Abstract »|Full Text »|PDF »
Lateral Mobility of Nicotinic Acetylcholine Receptors on Neurons Is Determined by Receptor Composition, Local Domain, and Cell Type.
C. C. Fernandes, D. K. Berg, and D. Gomez-Varela (2010)
J. Neurosci.
30, 8841-8851
|Abstract »|Full Text »|PDF »
Synchronous and Asynchronous Transmitter Release at Nicotinic Synapses Are Differentially Regulated by Postsynaptic PSD-95 Proteins.
R. A. Neff III, W. G. Conroy, J. D. Schoellerman, and D. K. Berg (2009)
J. Neurosci.
29, 15770-15779
|Abstract »|Full Text »|PDF »
Nicotinic Receptors Concentrated in the Subsynaptic Membrane Do Not Contribute Significantly to Synaptic Currents at an Embryonic Synapse in the Chicken Ciliary Ganglion.
Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function.
E. X. Albuquerque, E. F. R. Pereira, M. Alkondon, and S. W. Rogers (2009)
Physiol Rev
89, 73-120
|Abstract »|Full Text »|PDF »
Spontaneous and Evoked Glutamate Release Activates Two Populations of NMDA Receptors with Limited Overlap.
D. Atasoy, M. Ertunc, K. L. Moulder, J. Blackwell, C. Chung, J. Su, and E. T. Kavalali (2008)
J. Neurosci.
28, 10151-10166
|Abstract »|Full Text »|PDF »
Cell++--simulating biochemical pathways.
C. Sanford, M. L.K. Yip, C. White, and J. Parkinson (2006)
Bioinformatics
22, 2918-2925
|Abstract »|Full Text »|PDF »
Excitation of rat hippocampal interneurons via modulation of endogenous agonist activity at the {alpha}7 nicotinic ACh receptor.
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. 
To whom correspondence should be addressed: 
