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The Journal of Neuroscience, July 5, 2006, 26(27):7212-7221; doi:10.1523/JNEUROSCI.1450-06.2006
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Neurobiology of Disease
Synapse Formation and Function Is Modulated by the Amyloid Precursor Protein
Christina Priller, Thomas Bauer, Gerda Mitteregger, Bjarne Krebs, Hans A. Kretzschmar, andJochen Herms Zentrum für Neuropathologie und Prion Forschung, Ludwig Maximilians Universität, 81377 Munich, Germany
Correspondence should be addressed to Dr. Jochen Herms, Zentrum für Neuropathologie, Ludwig Maximilians Universität, Feodor-Lynen Strasse 23, 81377 Munich, Germany. Email: jochen.herms{at}med.uni-muenchen.de
The amyloid precursor protein (APP) is critical in the pathogenesis of Alzheimer's disease. The question of its normal biological function in neurons, in which it is predominantly located at synapses, is still unclear. Using autaptic cultures of hippocampal neurons, we demonstrate that hippocampal neurons lacking APP show significantly enhanced amplitudes of evoked AMPA- and NMDA-receptor-mediated EPSCs. The size of the readily releasable synaptic vesicle pool was also increased in neurons lacking APP, whereas the release probability was not affected. In addition, the analysis of spontaneous miniature synaptic currents revealed an augmented frequency in neurons lacking APP, whereas the amplitude of miniature synaptic currents was not found to be altered. Together, these findings strongly indicate that lack of APP increases the number of functional synapses. This hypothesis is further supported by morphometric immunohistochemical analysis revealing an increase of synaptophysin-positive puncta per cultured APP knock-out neuron. In conclusion, lack of APP affects synapse formation and transmission in cultured hippocampal neurons.
Key words: amyloid precursor protein; Alzheimer's disease; synaptic transmission; amyloid; synaptic vesicle; patch clamp
Received Nov. 30, 2005; revised May 18, 2006; accepted May 18, 2006.
Correspondence should be addressed to Dr. Jochen Herms, Zentrum für Neuropathologie, Ludwig Maximilians Universität, Feodor-Lynen Strasse 23, 81377 Munich, Germany. Email: jochen.herms{at}med.uni-muenchen.de
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