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Published online
doi:10.1083/jcb.1815iti3
The Journal of Cell Biology, Vol. 181, No. 5, 712-
The Rockefeller University Press, 0021-9525 $30.00
© Leslie
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Slow synapses in schizophrenia?



Figure 1
Vesicles ready for release (arrows) cluster at a synapse in a hippocampal neuron.

The hallucinations, delusions, and confused thinking of schizophrenia might result from sluggish synapses, as Chen et al. reveal. The team found that neurotransmitter release slowed in mice missing a protein that's also scarce in many schizophrenia patients.

Scientists have long suspected that synaptic transmission is faulty in schizophrenia. Clues to the mechanism might come from schizophrenia susceptibility genes, one of which codes for the synaptic protein dysbindin. Although scientists haven't identified any dysbindin mutants in schizophrenia patients, lower levels of the protein in two brain areas, the hippocampus and the prefrontal cortex, might produce the disease's symptoms. Chen et al. tested mutant mice that lack dysbindin (known as "sandy" mice) to determine how loss of the protein alters synaptic transmission.

Transmission across the synapse involves the release of neurotransmitter vesicles. The researchers first asked whether vesicle release in general was affected in sandy mice, by studying the animal's adrenal gland cells—commonly used models for vesicle dynamics. Applying a technique called amperometry, which detects discharge of individual vesicles, the team found that although vesicles were larger than normal in sandy mice, vesicle release took longer and the odds of a particular vesicle unloading its contents were lower. The researchers then saw a similar pattern in hippocampal neurons from sandy mice: larger vesicles but tardy release.

Neurotransmitter vesicles poised for release line up on the presynaptic side of the neuron. But neurons from sandy mice showed fewer of these vesicles than did control cells. The changes Chen et al. identified could impair a neuron's ability to relay a message. The next step is to determine whether synapses in schizophrenia patients show similar changes. Formula

Chen, X.-W., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200711021.[Abstract/Free Full Text]



Mitch Leslie

mitchleslie{at}comcast.net


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This Article
Right arrow Full Text (PDF, 764K)
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