P2‐243: IMPAIRMENTS IN NEURAL CORRELATES OF CONTEXTUAL MEMORY IN A MOUSE MODEL OF AMYLOIDOPATHY

Abstract

One of the brain areas affected earliest in Alzheimer's disease 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. Theta oscillations evoke nested gamma oscillations, resulting in a theta-gamma phase-amplitude coupling (PAC) that increases with running speed in the hippocampus. 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. 6 months old male J20 and wild-type (WT) mice were surgically implanted with recording probes in the dorsal MEC. Following a recovery period, mice were placed in an open arena (either circular or square, of equal area) and encouraged to explore it for 15 minutes twice a day, for 4 days. On the fifth day all mice were then placed in a novel arena. During these exploration periods, mice were tethered to a multi-channel recording system and the local field potentials in the MEC acquired. As the environment became more familiar, the slope of theta frequency vs running speed increased in WT mice. However, in J20 mice no changes were observed. Equivalent effects were observed in the gamma frequency and power vs running speed relationships, whereby the slope increased with familiarity in WT mice, unlike J20 mice which showed no significant changes. Theta-gamma PAC rose with running speed in WT mice but not in J20 mice, where the overall PAC was reduced. These results provide evidence of a significant disruption to the neuronal network mechanism underlying spatial contextual memory and speed encoding in a mouse model of amyloidopathy.