Impaired theta-gamma coupling in APP-deficient mice

• DOI: 10.1038/srep21948
• Publication Date: 2016-02-24T11:13:59Z
• Authors: Xiaomin Zhang; Wewei Zhong; Jurij Brankačk; Sascha W. Weyer; Ulrike C. Müller; Adriano B. L. Tort; Andreas Draguhn
• Keywords: Mice, Knockout; 0301 basic medicine; 570; 610; Prefrontal Cortex; amyloid precursor protein; Hippocampus; Article; Mice, Inbred C57BL; Stereotaxic Techniques; Amyloid beta-Protein Precursor; Mice; 03 medical and health sciences; Parietal Lobe; Animals; Gamma Rhythm; Cognitive Dysfunction; theta-gamma; Alzheimer disease; Nerve Net; Theta Rhythm

AbstractAmyloid 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.