Reduced entorhinal and dentate theta-gamma coupling associated with adult Reelin loss in Alzheimer’s disease relevant mice

Early Alzheimer’s disease (AD) affects entorhinal-hippocampal circuits, motivating functional measures of altered network coordination. We examined local field potentials and multiunit activity in head-fixed mice in a virtual-reality (VR) environment, comparing WT, App NL-F , and App NL-F -Reln-cKO groups ( n = 3 male mice per genotype). Reelin deletion was induced in adulthood using a ubiquitous tamoxifen-inducible Cre driver and was not restricted to entorhinal cortex (EC). Recordings sampled EC, dentate gyrus (DG), and CA1. Theta–gamma phase–amplitude coupling was quantified using modulation index (MI) and phase-locking value (PLV) between theta phase and the phase of the gamma-amplitude envelope. Nominal genotype effects were detected for DG-theta/DG-gamma coupling (MI, p = 0.034; PLV, p = 0.035) and EC-theta/DG-gamma coupling (MI, p = 0.0043; PLV, p = 0.0079), with descriptively lower means in App NL-F -Reln-cKO mice. Regional power spectra appeared broadly similar; a nominal genotype effect was reported for DG theta power ( p = 0.029), rather than a selective DG gamma-power reduction. Exploratory analyses suggested stronger coupling attenuation in the 35–55-Hz range and lower DG-associated coupling in both high and low theta/delta states. These findings identify DG-associated theta–gamma coupling as a candidate functional readout of adult Reelin loss in an AD-relevant background. The small cohort, uncorrected comparisons, widespread deletion, and absence of coupling–behavior analyses limit anatomical and functional inference.