The retrosplenial cortex (RSC) plays a significant role in spatial learning and memory and is functionally disrupted in the early stages of Alzheimer's disease (AD). In order to investigate neurophysiological correlates of spatial learning and memory in this region we employed in vivo electrophysiology in awake and freely moving male mice, comparing neural activity between wild-type and J20 mice, a transgenic model of AD-associated amyloidopathy. To determine the response of the RSC to environmental novelty local field potentials (LFPs) were recorded while mice explored novel and familiar recording arenas. In familiar environments we detected short, phasic bursts of β (20–30 Hz) oscillations (β bursts), which arose at a low but steady rate. Exposure to a novel environment rapidly initiated a dramatic increase in the rate, size and duration of β bursts. Additionally, θ-α/β cross-frequency coupling was significantly higher during novelty, and spiking of neurons in the RSC was significantly enhanced during β ...