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

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.

journal_name

Neuron

journal_title

Neuron

authors

Šišková Z,Justus D,Kaneko H,Friedrichs D,Henneberg N,Beutel T,Pitsch J,Schoch S,Becker A,von der Kammer H,Remy S

doi

10.1016/j.neuron.2014.10.024

subject

Has Abstract

pub_date

2014-12-03 00:00:00

pages

1023-33

issue

5

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(14)00922-2

journal_volume

84

pub_type

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