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The Journal of Neuroscience, June 6, 2007, 27(23):6224-6233; doi:10.1523/JNEUROSCI.5062-06.2007

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Neurobiology of Disease
Dendritic Pathology in Prion Disease Starts at the Synaptic Spine

Martin Fuhrmann, Gerda Mitteregger, Hans Kretzschmar, and Jochen Herms

Center of Neuropathology and Prion Research, Ludwig Maximilians University, 81377 Munich, Germany

Correspondence should be addressed to Dr. Jochen Herms, Center of Neuropathology and Prion Research, Ludwig Maximilians University Munich, 81377 Munich, Germany. Email: Jochen.Herms{at}med.uni-muenchen.de

Spine loss represents a common hallmark of neurodegenerative diseases. However, little is known about the underlying mechanisms, especially the relationship between spine elimination and neuritic destruction. We imaged cortical dendrites throughout a neurodegenerative disease using scrapie in mice as a model. Two-photon in vivo imaging over 2 months revealed a linear decrease of spine density. Interestingly, only persistent spines (lifetime 8 d) disappeared, whereas the density of transient spines (lifetime 4 d) was unaffected. Before spine loss, dendritic varicosities emerged preferentially at sites where spines protrude from the dendrite. These results implicate that the location where the spine protrudes from the dendrite may be particularly vulnerable and that dendritic varicosities may actually cause spine loss.

Key words: structural plasticity; spine; dendrite; prion; somatosensory cortex; two-photon

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Received Nov. 22, 2006; revised April 17, 2007; accepted April 21, 2007.

Correspondence should be addressed to Dr. Jochen Herms, Center of Neuropathology and Prion Research, Ludwig Maximilians University Munich, 81377 Munich, Germany. Email: Jochen.Herms{at}med.uni-muenchen.de

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