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The synapse is a shotgun

ter of neurons that connect the brain to the iris of the eye. It launches the neurotransmitter acetylcholine from sac-like vesicles across the synapse to two types of receptors, called alpha 7 and alpha 3.

Sejnowski and his colleagues transformed their map into a functional computer model by incorporating the physiological details of neurotransmitter release sites and receptors. The researchers then compared the behavior of the model under different scenarios with the electrophysiological behavior of actual ganglia measured in Berg's laboratory.

The results, said Sejnowski, provide evidence for a different concept of the synapse. "The image of this ganglion is not one of a simple synapse with a single release site, but multiple release sites. And it shows alpha 3 receptors within the postsynaptic region, but alpha 7 receptors outside this region. Our model showed that if we assumed that neurotransmitter is released only from vesicles in active zones, where everybody thinks it is released, we get a very bad match to actual properties of the neuron. But if we model broader neurotransmitter release, where these alpha 7 receptors are located, we can match the actual properties of the synapse very accurately." This type of broader neurotransmitter distribution is called ectopic release.

"We can only be sure of data on this one type of neuron, the ciliary ganglion," said Sejnowski. "But we are confident that this evidence points to ectopic release, and this means that you can't really trust the traditional textbook view -- in which all the vesicles are released at the active zone -- that's taken for granted now."

The function of shotgun neurotransmitter release is unknown, said Sejnowski. "There's just nothing solid on our radar screen right now," he said. "There is speculation that ectopic release represents some sort of spillover that neurons use under certain circumstances. Or, it may be an alternative mode of neurotransmission that neur
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Source:Howard Hughes Medical Institute


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