Beta bursting in the retrosplenial cortex is a neurophysiological correlate of environmental novelty which is disrupted in a mouse model of Alzheimer's disease

This is the author accepted manuscript. The final version is available from the Society for Neuroscience via the DOI in this recordThe retrosplenial cortex (RSC) plays a significant role in spatial learning and memory and is functionally disrupted in the early stages of Alzheimer's disease. 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 Alzheimer's disease-associated amyloidopathy. To determine the response of the RSC to environmental novelty local field potentials were recorded while mice explored novel and familiar recording arenas. In familiar environments we detected short, phasic bursts of beta (20-30 Hz) oscillations (beta 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 beta bursts. Additionally, theta-alpha/beta cross-frequency coupling was significantly higher during novelty, and spiking of neurons in the RSC was significantly enhanced during beta bursts. Finally, excessive beta bursting was seen in J20 mice, including increased beta bursting during novelty and familiarity, yet a loss of coupling between beta bursts and spiking activity. These findings support the concept that beta bursting may be responsible for the activation and reactivation of neuronal ensembles underpinning the formation and maintenance of cortical representations, and that disruptions to this activity in J20 mice may underlie cognitive impairments seen in these animals.SIGNIFICANCE STATEMENTThe retrosplenial cortex is thought to be involved in the formation, recall and consolidation of contextual memory. The discovery of bursts of beta oscillations in this region, which are associated with increased neuronal spiking and strongly upregulated while mice explore novel environments, provides a potential mechanism for the activation of neuronal ensembles, which may underlie the formation of cortical representations of context. Excessive beta bursting in the retrosplenial cortex of J20 mice, a mouse model of Alzheimer's disease, alongside the disassociation of beta bursting from neuronal spiking, may underlie spatial memory impairments previously shown in these mice. These findings introduce a novel neurophysiological correlate of spatial learning and memory, and a potentially new form of Alzheimer's disease related cortical dysfunction.University of ExeterJanssen PharmaceuticaAlzheimer’s Research U