Impaired theta-gamma coupling in APP-deficient mice

Amyloid precursor protein (APP) is critically involved in the pathophysiology of Alzheimer’s disease, but its physiological functions remain elusive. Importantly, APP knockout (APP-KO) mice exhibit cognitive deficits, suggesting that APP plays a role at the neuronal network level. To investigate thi...

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Bibliographic Details
Published in:Scientific reports 2016-02, Vol.6 (1), p.21948, Article 21948
Main Authors: Zhang, Xiaomin, Zhong, Wewei, Brankačk, Jurij, Weyer, Sascha W., Müller, Ulrike C., Tort, Adriano B. L., Draguhn, Andreas
Format: Article
Language:English
Subjects:
631/378/1689/1283
631/378/3920
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Alzheimer's disease
Amyloid beta-Protein Precursor - deficiency
Amyloid beta-Protein Precursor - genetics
Amyloid precursor protein
Animals
Cognitive ability
Cognitive Dysfunction - genetics
Cognitive Dysfunction - physiopathology
Cortex (parietal)
Gamma Rhythm
Hippocampus
Hippocampus - physiopathology
Humanities and Social Sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
multidisciplinary
Nerve Net - physiopathology
Neurodegenerative diseases
Parietal Lobe - physiopathology
Prefrontal cortex
Prefrontal Cortex - physiopathology
Rodents
Science
Stereotaxic Techniques
Theta Rhythm
Theta rhythms
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Summary:Amyloid precursor protein (APP) is critically involved in the pathophysiology of Alzheimer’s disease, but its physiological functions remain elusive. Importantly, APP knockout (APP-KO) mice exhibit cognitive deficits, suggesting that APP plays a role at the neuronal network level. To investigate this possibility, we recorded local field potentials (LFPs) from the posterior parietal cortex, dorsal hippocampus and lateral prefrontal cortex of freely moving APP-KO mice. Spectral analyses showed that network oscillations within the theta- and gamma-frequency bands were not different between APP-KO and wild-type mice. Surprisingly, however, while gamma amplitude coupled to theta phase in all recorded regions of wild-type animals, in APP-KO mice theta-gamma coupling was strongly diminished in recordings from the parietal cortex and hippocampus, but not in LFPs recorded from the prefrontal cortex. Thus, lack of APP reduces oscillatory coupling in LFP recordings from specific brain regions, despite not affecting the amplitude of the oscillations. Together, our findings reveal reduced cross-frequency coupling as a functional marker of APP deficiency at the network level.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep21948