Bursts of beta oscillations across the brain as a neurophysiological correlate of contextual novelty

Abstract

The retrosplenial cortex and hippocampus are brain regions which have been shown to be highly involved in contextual memory. In order to discover neurophysiological correlates of contextual memory in these regions, we used in vivo electrophysiology in awake, behaving mice while they explored a series of novel and familiar environments. Additionally, in order to better understand the specific neurophysiological effects of Alzheimer’s disease-associated amyloid pathology on the retrosplenial cortex and hippocampus, we compared network activity between wild-type mice and J20 mice, a transgenic mouse model which develops widespread age-related amyloid pathology and memory impairments. We detected transient bursts of beta oscillations in both the retrosplenial cortex and hippocampus that were synchronous between these regions and upregulated during contextual novelty. Moreover, spiking of neurons in the retrosplenial cortex was significantly increased during beta bursts. In J20 mice, we noted numerous examples of altered network activity, including aberrant beta bursting which is not coupled to neuronal spiking. Through the use of EEG recordings in mice, we demonstrated that beta bursts can be detected across the cortex, and are highly synchronous between different brain regions. Finally, we demonstrated that it is possible to pharmacologically induce beta bursting in the retrosplenial cortex in vitro through the use of carbachol, a muscarinic acetylcholine receptor agonist, providing an assay for better understanding the mechanisms underlying beta bursting. These findings suggest that transient beta bursting across the brain provides brief windows of effective communication between brain regions, which may underlie the formation of cortical representation of contexts, and may be impaired in Alzheimer’s disease