Breakdown of functional networks in mouse models of dementia

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the major cause of dementia, for which there are no available treatments that can cure or stop its progression. Disorientation in both familiar and unfamiliar places is a symptom often observed in people affected by AD. The entorhinal cortex (EC), which is one of the brain areas earliest affected by this disease, plays a key role in spatial navigation and memory. Despite the important role that the EC may play in the spatial memory deficits observed in AD, the effects of novelty and familiarity on the EC neuronal dynamics of amyloidopathy mouse models is not well understood. This PhD thesis focuses on the study of the medial EC (MEC) neuronal dynamics underlying spatial memory in an amyloidopathy mouse model, the J20 mice, employing in vivo electrophysiological techniques. Chapters 3 and 4 examine local field potential (LFP) signals to study the effects of novelty and familiarity on the MEC neuronal networks of J20 mice. These two chapters highlight deficits in high gamma oscillations in the MEC of these mice related to memory processing. Chapter 4 further examines the single-unit activity of the neurons involved in these networks in the MEC of J20 mice, during the exploration of novel and familiar environments. This chapter shows that theta modulated cells have a lower frequency of modulation in the MEC of these mice. Furthermore, the results of this chapter suggest that a proportion of functional cell subtypes are affected by the novelty of the environment in the MEC.