Abstract Body

Injection of prion brain homogenate into mice induces memory deficits, progressive neuronal loss and terminal disease. Pharmacological interventions can extend survival and preserve species-specific behaviour, but it is unclear whether neural activity is preserved. Here, we define oscillatory changes in the murine prion model in order to inform future studies of the effects of interventions on neural activity.

Prion and control-inoculated mice implanted with seven surface electrodes underwent weekly wireless recording from 4 weeks post-inoculation. Recordings were made until prion mice exhibited clinical signs of disease, 9–12 weeks post-inoculation. At this point, mice were humanely killed and brains retained for histological analysis. Decibel power spectra were generated from recordings using a 2.5 s sliding window with 50% overlap. Peak theta frequency and area under the curve measures were extracted (Figure 1). Effects of prion and week post-inoculation were determined using mixed effects analyses.

Prion mice exhibited a progressive reduction in peak theta frequency, which differed from control mice at 8- and 9-weeks post-inoculation (Figure 1). Prion mice with peak theta frequency >7.0 Hz at 9 weeks post-inoculation survived 10–25 days longer than mice <6.5 Hz. Area under the curve measures were similar between groups except for delta power, which showed a week by inoculation interaction.

The murine prion model exhibits a slowing of theta oscillatory activity and altered delta power, which are common to human neurodegenerative diseases including Alzheimer’s disease. This validates the use of the prion model to investigate potential disease modifying effects of interventions aimed at treating Alzheimer’s disease and related dementias.