title: Impaired theta-gamma coupling in APP-deficient mice.
abstract: 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.
authors.affiliation: Institute for Physiology and Pathophysiology, Heidelberg University, Heidelberg, Germany.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute for Physiology and Pathophysiology, Heidelberg University, Heidelberg, Germany.
authors.forename: Wewei
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Institute for Physiology and Pathophysiology, Heidelberg University, Heidelberg, Germany.
authors.forename: Jurij
authors.initials: J
authors.lastname: Brankačk
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Department of Bioinformatics and Functional Genomics, Heidelberg University, Heidelberg, Germany.
authors.forename: Sascha W
authors.initials: SW
authors.lastname: Weyer
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Department of Bioinformatics and Functional Genomics, Heidelberg University, Heidelberg, Germany.
authors.forename: Ulrike C
authors.initials: UC
authors.lastname: Müller
authors.affiliation: Brain Institute, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: Adriano B L
authors.initials: AB
authors.lastname: Tort
authors.affiliation: Institute for Physiology and Pathophysiology, Heidelberg University, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Draguhn
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D060825:Cognitive Dysfunction / Q000235:genetics / Q000503:physiopathology*; D065818:Gamma Rhythm; D006624:Hippocampus / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009415:Nerve Net / Q000503:physiopathology; D010296:Parietal Lobe / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology; D013238:Stereotaxic Techniques; D013826:Theta Rhythm
chemical_list: D016564:Amyloid beta-Protein Precursor