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Neuron. 2014 Dec 3;84(5):1023-33. doi: 10.1016/j.neuron.2014.10.024. Epub 2014 Nov 13.

Dendritic structural degeneration is functionally linked to cellular hyperexcitability in a mouse model of Alzheimer's disease.

Author information

1
Neuronal Networks Group, Deutsches Zentrum für Neurodegenerative Erkrankungen, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
2
Section of Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53125 Bonn, Germany.
3
Section of Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53125 Bonn, Germany; Department of Epileptology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53125 Bonn, Germany.
4
Neurobiology, Evotec AG, Essener Bogen 7, 22419 Hamburg, Germany.
5
Neuronal Networks Group, Deutsches Zentrum für Neurodegenerative Erkrankungen, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany; Department of Epileptology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53125 Bonn, Germany. Electronic address: stefan.remy@dzne.de.

Abstract

Dendritic structure critically determines the electrical properties of neurons and, thereby, defines the fundamental process of input-to-output conversion. The diversity of dendritic architectures enables neurons to fulfill their specialized circuit functions during cognitive processes. It is known that this dendritic integrity is impaired in patients with Alzheimer's disease and in relevant mouse models. It is unknown, however, whether this structural degeneration translates into aberrant neuronal function. Here we use in vivo whole-cell patch-clamp recordings, high-resolution STED imaging, and computational modeling of CA1 pyramidal neurons in a mouse model of Alzheimer's disease to show that structural degeneration and neuronal hyperexcitability are crucially linked. Our results demonstrate that a structure-dependent amplification of synaptic input to action potential output conversion might constitute a novel cellular pathomechanism underlying network dysfunction with potential relevance for other neurodegenerative diseases with abnormal changes of dendritic morphology.

PMID:
25456500
DOI:
10.1016/j.neuron.2014.10.024
[Indexed for MEDLINE]
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