Ripple-Associated Hippocampal Activity and Recognition Memory in Rats during Rest

Abstract

The hippocampus, has been established as a key structure in the processing of memory operations, with its neural activity proposed to play a critical role in memory consolidation. Memory impairment is prevalent in schizophrenia, with abnormal hippocampal structure being one of the most robust findings among diagnosed patients. This observation led to the hypothesis that hippocampal neural activity would show abnormalities as well, which possibly is associated to the memory impairment displayed in schizophrenia. Therefore, the current study, with the aid of a neurodevelopmental animal model of schizophrenia (MIA), aimed to investigate whether memory deficits are a consequence of altered hippocampal neural activity, specifically the sharp-wave ripples that occur during rest periods. It was hypothesized that a) the MIA rats would show impairment on a hippocampal-dependent memory task (displaced objects), compared to control rats due to the hippocampus being dysfunctional in the MIA model of schizophrenia, and b) ripple characteristics (i.e., duration, percentage, and rate of ripple) would differ in the MIA rats which would be related to the predicted deficit in their ability to discriminate between displaced and non-displaced objects. Eight MIA and eight control rats were trained on an object recognition memory paradigm consecutively for three days, at the end of which their ability to discriminate between displaced and non-displaced objects was assessed. In addition, an hour of hippocampal-ripple activity was recorded immediately after interaction with the objects while the animal was in a resting state. The main findings of this study were a) an intact memory for object recognition was found in both group of rats; contrary to our hypothesis, and b) all measures of ripple activity were found to be significantly elevated in the MIA rats, compared to controls, supporting the first part of our second hypothesis. Further analysis revealed a negative correlation between two of the three ripple measures recorded after the day 2, familiar object exposure procedure, and object discrimination performance measure acquired during the test phase, when the analysis included both MIA and control animals. When the two groups were analyzed separately, it was only the control group that displayed a significant relationship. This suggests that ripples in the MIA animals may have been to a certain extent, pathological, no longer relating to memory performance. Further research utilizing various other memory paradigms could shed more light on the current findings.