Proceedings of The Physiological Society

Experimental Models (Exeter, UK) (2018) Proc Physiol Soc 40, PC04

Poster Communications

Impairments in neural correlates of contextual memory in a mouse model of amyloidopathy

M. Garcia Garrido1, T. Ridler1, J. Terry2, J. T. Brown1

1. Institute of Biomedical and Clinical Sciences, Medical School, University of Exeter, Exeter, United Kingdom. 2. College of Engineering, Mathematics and physical sciences, University of Exeter, Exeter, United Kingdom.

Impairments in spatial navigation and memory are present at an early stage in Alzheimer's disease (AD). One of the brain areas affected earliest in AD is the medial entorhinal cortex (MEC), which plays a key role in the neural encoding of spatial information via a variety of functional subclasses of neurons. The activity of many of these cell types is strongly modulated by theta frequency (6-12 Hz) oscillations, the power and frequency of which increase with the speed at which the animal is moving. Gamma frequency (30-120 Hz) oscillations are also dependent on running speed. Previous work suggests that the running speed-theta frequency relationship is steeper in familiar environments than in novel ones, suggesting a neural correlate of contextual spatial memory. Despite the important role that the MEC plays in spatial navigation and memory, the effects of novel and familiar environmental stimuli on the MEC neuronal dynamics in mouse models of amyloidopathy remain unexplored. We have investigated this electrophysiological correlate of contextual memory in the J20 mice. 5-6 months old male J20 (n=8) and wild-type (WT) (n=7) mice were anaesthetised via isoflurane (2%) inhalation and surgically implanted with recording probes in the dorsal MEC. Following a recovery period, mice were placed in an open arena and encouraged to explore it for 15 minutes twice a day, for 4 days. On the fifth day all mice were placed in a novel arena. During each of these exploration periods, mice were tethered to a multi-channel recording system and the local field potential signals in the MEC acquired. All data are presented as mean ± SEM. A repeated measures ANOVA revealed a significant interaction between genotype and recording day in the slope of theta frequency vs running speed relationships (p<0.005). Pairwise comparisons showed that the slope of theta frequency vs running speed increased with familiarity in WT mice (0.001 ± 0.007 Hz/cms-1 day 1 vs. 0.032 ± 0.006 Hz/cms-1 day 4, p<0.005; 0.032 ± 0.006 Hz/cms-1 day 4 vs. 0.008 ± 0.004 Hz/cms-1 day 5, p<0.05). In contrast, in J20 mice there was no significant pairwise difference between recording days, suggesting significant impairments in the neural mechanisms encoding environmental familiarity. Equivalent effects were observed in the high gamma power (60-120 Hz) vs running speed relationship, whereby there was a significant interaction between genotype and day (p<0.05, repeated measures ANOVA). Similarly, pairwise comparisons showed an increase of the slope with familiarity in WT mice (8.3 ± 6.5 mV2Hz-1/cms-1 day 1 vs. 36.7 ± 12.3 mV2Hz-1/cms-1 day 4, p<0.005; 36.7 ± 12.3 mV2Hz-1/cms-1 day 4 vs. 20.4 ± 9.6 mV2Hz-1/cms-1 day 5, p<0.05) whilst in J20 mice there were no significant changes. These results provide evidence of a significant disruption to the neuronal network mechanism underlying spatial contextual memory in J20 mice.

Where applicable, experiments conform with Society ethical requirements