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01-04-2019 | Alzheimer's Disease | Original Article

Lack of β-amyloid cleaving enzyme-1 (BACE1) impairs long-term synaptic plasticity but enhances granule cell excitability and oscillatory activity in the dentate gyrus in vivo

Authors: Matej Vnencak, Marieke L. Schölvinck, Stephan W. Schwarzacher, Thomas Deller, Michael Willem, Peter Jedlicka

Published in: Brain Structure and Function | Issue 3/2019

Abstract

BACE1 is a β-secretase involved in the cleavage of amyloid precursor protein and the pathogenesis of Alzheimer’s disease (AD). The entorhinal cortex and the dentate gyrus are important for learning and memory, which are affected in the early stages of AD. Since BACE1 is a potential target for AD therapy, it is crucial to understand its physiological role in these brain regions. Here, we examined the function of BACE1 in the dentate gyrus. We show that loss of BACE1 in the dentate gyrus leads to increased granule cell excitability, indicated by enhanced efficiency of synaptic potentials to generate granule cell spikes. The increase in granule cell excitability was accompanied by prolonged paired-pulse inhibition, altered network gamma oscillations, and impaired synaptic plasticity at entorhinal-dentate synapses of the perforant path. In summary, this is the first detailed electrophysiological study of BACE1 deletion at the network level in vivo. The results suggest that BACE1 is important for normal dentate gyrus network function. This has implications for the use of BACE1 inhibitors as therapeutics for AD therapy, since BACE1 inhibition could similarly disrupt synaptic plasticity and excitability in the entorhinal–dentate circuitry.

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Title: Lack of β-amyloid cleaving enzyme-1 (BACE1) impairs long-term synaptic plasticity but enhances granule cell excitability and oscillatory activity in the dentate gyrus in vivo
Authors: Matej Vnencak
Marieke L. Schölvinck
Stephan W. Schwarzacher
Thomas Deller
Michael Willem
Peter Jedlicka
Publication date: 01-04-2019
Publisher: Springer Berlin Heidelberg
Keywords: Alzheimer's Disease
Alzheimer's Disease
Published in: Brain Structure and Function / Issue 3/2019
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-019-01836-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Lack of β-amyloid cleaving enzyme-1 (BACE1) impairs long-term synaptic plasticity but enhances granule cell excitability and oscillatory activity in the dentate gyrus in vivo

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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