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Two distinct pools of synaptic vesicles appear to be involved in the spontaneous release of neurotransmitters and in neurotransmission triggered by a stimulus, researchers report in Neuron this week. Their findings raise questions about a fundamental theory of neurotransmission developed by Bernard Katz.
Ege T. Kavalali and colleagues from the University of Texas (UT) Southwestern Medical Center studied the spontaneous fusion of synaptic vesicles in rat hippocampal cells, using dyes that fluoresce when inside a cell membrane.
The researchers found that when vesicles were allowed to fill in the absence of network activity and then subjected to stimulation, loss of dye was slow. When activity was induced, vesicle destaining showed an initial rapid phase, then slowed to the rate of spontaneously loaded vesicles.
Their conclusion was that there may be two types of recycling vesicles. Spontaneously recycling vesicles are reluctant to release neurotransmitters during stimulation, but do so readily in the absence of activity. Activity-dependent vesicles show the reverse pattern.
"These findings question one of the core tenets of synaptic function and reveal significant complexity in organization of synaptic vesicles within individual synapses," Kavalali said in a statement.
This conclusion challenges the "quantal" model of neurotransmission, which assumes that active release of neurotransmitters and spontaneous release ("miniature synaptic potentials") use the same pools of vesicle.
"The conclusion is reasonably sound," said Ling-Gang Wu of the National Institute of Neurological Disorders and Stroke, who was not involved in the study. "The evidence is quite good, although it is not direct evidence, and the separation between spontaneous and evoked release is not complete."
In a preview article accompanying the UT paper, Robert S. Zucker of the University of California, Berkeley, points out that the quantal hypothesis is not invalidated, but that its assumptions must be now be tested when spontaneous neuron potentials are analyzed.
"Certainly, the plot thickens," commented Timothy H. Murphy of the University of British Columbia, via E-mail. The results raise the question of whether miniature synaptic potentials reflect accidental release at synapses with a hair trigger for evoked release or a background form of transmission cycling within their own vesicle pool, he said.
One of the significant questions, Kavalali told The Scientist, is "How do vesicles end up in this situation?" Kavalali's group has already taken a step toward identifying the mechanisms responsible. Mice engineered to lack synaptobrevin-2, a protein component of synaptic vesicles, showed no evidence of activity-dependent recycling, he said.
References
| 1. | | [http://www.the-scientist.com/2004/10/25/17/1]
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| | | J.U. Adams, "Synaptic vesicles: Reused or recycled?" The Scientist, October 25, 2004.
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| 2. | | [http://www.neuron.org]
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| | | S. Yildirim et al., "An isolated pool of vesicles recycles at rest and drives spontaneous neurotransmission," Neuron, 45:563-73, February 17, 2005.
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| 3. | | [http://nobelprize.org/medicine/laureates/1970/katz-lecture.pdf]
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| | | B. Katz, "On the quantal mechanism of neural transmitter release," Nobel lecture, December 12, 1970.
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| 4. | | [http://www.the-scientist.com/news/20030430/02]
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| | | S. Mayor, "Bernard Katz dies," The Scientist, April 30, 2003.
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| 5. | | [http://www8.utsouthwestern.edu/utsw/cda/dept120915/files/150823.html]
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| | | Ege T. Kavalali
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| 6. | | [http://neuroscience.nih.gov/Lab.asp?Org_ID=497]
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| | | Ling-Gang Wu
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| 7. | | [http://www.neuron.org]
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| | | R. S. Zucker, "Minis: Whence and wherefore? Neuron, 45:482-4, February 17, 2005.
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| 8. | | [http://mcb.berkeley.edu/labs/zucker/]
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| | | Robert S. Zucker
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| 9. | | [http://www.interchg.ubc.ca/neurosci/faculty/murphy.html]
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| | | Timothy H. Murphy
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| 10. | | O. Prange, T.H. Murphy, "Correlation of miniature synaptic activity and evoked release probability in cultures of cortical neurons," J Neurosci, 19:6427-38, August 1, 1999.
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