Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.783682
Title: Black box effect : investigating the role of retroactive interference on hippocampal memory mechanisms
Author: Arkell, Daisy
ISNI:       0000 0004 7969 266X
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2019
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Abstract:
Recent studies have shown that decreasing sensory stimulation after learning can enhance memory retention in humans. Amnesic patients and healthy controls expressed significantly better memory for both passages of prose and spatial landmarks when learning was followed by a short period filled with restful wake, rather than an unrelated distractor task (Dewar et al, 2010; Craig et al, 2016). This enhancement was suggested to arise from decreases in memory interference processes. These findings suggest that interference from ongoing sensory stimulation could have a much larger impact on memory and everyday life than previously thought. The aim of this thesis was therefore to investigate the role of retroactive interference in hippocampal-dependent memory consolidation, and to explore the neural mechanisms behind this episodic memory enhancement. To this end, I tested the effects of reducing different types of interference after spatial learning on memory retention in rats. A spatial memory task was used that required no reward, instead using the animal's natural tendency to detect and explore novelty. To exploit this behaviour experimentally to test memory retention, I used the novel object location (nOL) recognition task. My protocol consisted of a single training trial, during which animals could explore two copies of the same novel object placed in an open field arena. Memory for the object locations was then tested 6h or 24h later, when animals were returned to the arena in which now one of these objects was moved to a novel location. Animals that preferred to explore the object at the novel location expressed memory for the location the objects occupied during the training trial. The role of interference on object location memory was assessed by exposing the animals to different, highly-familiar stimuli (i.e., dark or normally lit holding box, home cage, or cagemate in a holding box) during the 1 h period directly following the training trial. We used gentle handling to prevent rats from falling asleep during this period. I found that animals expressed robust nOL memory when exposed to a dark familiar holding box after learning, but not when they were exposed to their home cage, replicating the memory enhancement effect following reduction of visual stimulation seen in humans. Further experiments sought to isolate what aspects of the dark holding box promoted memory retention as compared to the home cage. To this end, after learning, animals were put into their home cages with their cage mates, which was placed in either an enclosed normally lit (white light) box (WB), or an enclosed dark (red light) box (RB). Neither group expressed memory, suggesting that the black box effect was dependent on animals being socially isolated. Exposure to the WB when alone also prevented the expression of nOL memory. Yet, animals exposed to the RB without cage mates expressed object location memory, establishing that the black holding box effect was dependent on animals being socially isolated and with reduced visual stimulation. These results suggested that interference not only stems from new learning, but can occur simply when exposed to either highly familiar social or visual stimuli. Object location memory is known to depend on the hippocampus. The activity of pyramidal neurons within the hippocampus (place cells) represents the location of an animal within its environment. This activity is context-dependent, and has been shown to be modulated by the manipulation of objects within these environments (Deshmukh et al, 2013; Burke et al, 2011). Therefore, to explore the neural mechanisms underpinning the 'black box effect', I recorded place cells in the dorsal CA1 of rats. I first focused on the spatially-selective firing of place cells to study whether post-learning stimulation could affect the spatial stability of place cell firing within a novel environment, thereby causing memory interference. Animals explored a novel environment for 10 min, after which they spent 3 h awake in either the WB or RB. Then, 6 h after the initial exposure, animals explored the same environment again. Analysis of place cell firing indicated that whilst the overall firing and spatial properties of place cells were not different between groups, the stability of place fields between the initial and repeated exposures was significantly enhanced in the dark (RB) box group. Therefore, reducing visual stimulation after learning promoted place field stability, consistent with the behavioural results. To determine whether these changes in place field stability correlated to the strength of object location memory, a third set of experiments investigated the influence of objects on place field expression during a nOL behavioural task. As seen previously, implanted rats expressed object location memory for 6 h when exposed to the RB, but not the WB, after learning. In contrast to these findings, no differences in the firing and spatial properties of place fields both over and between sessions were found between the WB and RB groups. The introduction, movement and removal of objects, however, did affect various measures of place field stability and synchronicity. The apparent object-place field relationship was investigated further, and results suggested that place fields were more likely to be expressed away from objects during the probe trial if the animal had significant memory for the object locations. Overall, the results reported in my thesis show that long-term memory formation, in terms of behavioural as well a subset of electrophysiological measures, benefits from reduced sensory stimulation after learning. These findings highlight that even low levels of sensory stimulation can have a drastic impact on spatial memory and correlated neural activity. This has important implications for experimental design, as well as life outside of the laboratory.
Supervisor: Wood, Emma ; Ribchester, Richard Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.783682  DOI: Not available
Keywords: memory ; retroactive interference ; memory retention ; wakeful rest ; hippocampus
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