[Murg] synaptic transmission queried

[Eugen Leitl]

http://www.biomedcentral.com/news/20050218/01

Synaptic transmission queried
Evidence disputes assumptions of quantum hypothesis | By Mitchell Maltenfort

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.
Links for this article
J.U. Adams, "Synaptic vesicles: Reused or recycled?" The Scientist, October
25, 2004.
http://www.the-scientist.com/2004/10/25/17/1 

S. Yildirim et al., "An isolated pool of vesicles recycles at rest and drives
spontaneous neurotransmission," Neuron, 45:563-73, February 17, 2005.
http://www.neuron.org 

B. Katz, "On the quantal mechanism of neural transmitter release," Nobel
lecture, December 12, 1970.
http://nobelprize.org/medicine/laureates/1970/katz-lecture.pdf 

S. Mayor, "Bernard Katz dies," The Scientist, April 30, 2003.
http://www.biomedcentral.com/news/20030430/02 

Ege T. Kavalali
http://www8.utsouthwestern.edu/utsw/cda/dept120915/files/150823 .html 

Ling-Gang Wu
http://neuroscience.nih.gov/Lab.asp?Org_ID=497 

R. S. Zucker, "Minis: Whence and wherefore? Neuron, 45:482-4, February 17,
2005.
http://www.neuron.org 

Robert S. Zucker
http://mcb.berkeley.edu/labs/zucker/ 

Timothy H. Murphy
http://www.interchg.ubc.ca/neurosci/faculty/murphy.html 

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.
[PubMed Abstract]  


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Eugen* Leitl <a href="http://leitl.org">leitl</a>
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