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Synapse loss in cortex of agrin-deficient mice after genetic rescue of perinatal death

Ksiazek, Iwona and Burkhardt, Constanze and Lin, Shuo and Seddik, Riad and Maj, Marcin and Bezakova, Gabriela and Jucker, Mathias and Arber, Silvia and Caroni, Pico and Sanes, Joshua R. and Bettler, Bernhard and Ruegg, Markus A.. (2007) Synapse loss in cortex of agrin-deficient mice after genetic rescue of perinatal death. Journal of Neuroscience, 27 (27). pp. 7183-7195.

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Official URL: http://edoc.unibas.ch/dok/A5262220

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Abstract

Agrin-deficient mice die at birth because of aberrant development of the neuromuscular junctions. Here, we examined the role of agrin at brain synapses. We show that agrin is associated with excitatory but not inhibitory synapses in the cerebral cortex. Most importantly, we examined the brains of agrin-deficient mice whose perinatal death was prevented by the selective expression of agrin in motor neurons. We find that the number of presynaptic and postsynaptic specializations is strongly reduced in the cortex of 5- to 7-week-old mice. Consistent with a reduction in the number of synapses, the frequency of miniature postsynaptic currents was greatly decreased. In accordance with the synaptic localization of agrin to excitatory synapses, changes in the frequency were only detected for excitatory but not inhibitory synapses. Moreover, we find that the muscle-specific receptor tyrosine kinase MuSK, which is known to be an essential component of agrin-induced signaling at the neuromuscular junction, is also localized to a subset of excitatory synapses. Finally, some components of the mitogen-activated protein (MAP) kinase pathway, which has been shown to be activated by agrin in cultured neurons, are deregulated in agrin-deficient mice. In summary, our results provide strong evidence that agrin plays an important role in the formation and/or the maintenance of excitatory synapses in the brain, and we provide evidence that this function involves MAP kinase signaling.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Physiology > Molecular Neurobiology Synaptic Plasticity (Bettler)
05 Faculty of Science > Departement Biozentrum > Neurobiology > Cell Biology (Arber)
05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Rüegg, Markus A. and Arber, Silvia and Bettler, Bernhard
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Society for Neuroscience
ISSN:0270-6474
e-ISSN:1529-2401
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:27 Nov 2017 15:34
Deposited On:22 Mar 2012 13:23

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