RT Journal Article
SR Electronic
T1 Synapse Loss in Cortex of Agrin-Deficient Mice after Genetic Rescue of Perinatal Death
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7183
OP 7195
DO 10.1523/JNEUROSCI.1609-07.2007
VO 27
IS 27
A1 Iwona Ksiazek
A1 Constanze Burkhardt
A1 Shuo Lin
A1 Riad Seddik
A1 Marcin Maj
A1 Gabriela Bezakova
A1 Mathias Jucker
A1 Silvia Arber
A1 Pico Caroni
A1 Joshua R. Sanes
A1 Bernhard Bettler
A1 Markus A. Ruegg
YR 2007
UL http://www.jneurosci.org/content/27/27/7183.abstract
AB 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.