Neurocognitive Aging: Prior memories hinder new hippocampal encoding

Department of Neuroscience and Neurology, University of Kuopio, Kuopio 70211, Finland.
Trends in Neurosciences (Impact Factor: 13.56). 01/2007; 29(12):662-70. DOI: 10.1016/j.tins.2006.10.002
Source: PubMed


Normal aging is often accompanied by impairments in forming new memories, and studies of aging rodents have revealed structural and functional changes to the hippocampus that might point to the mechanisms behind such memory loss. In this article, we synthesize recent neurobiological and neurophysiological findings into a model of the information-processing circuit of the aging hippocampus. The key point of the model is that small concurrent changes during aging strengthen the auto-associative network of the CA3 subregion at the cost of processing new information coming in from the entorhinal cortex. As a result of such reorganization in aged memory-impaired individuals, information that is already stored would become the dominant pattern of the hippocampus to the detriment of the ability to encode new information.

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    • "Hippocampal place cells (a type of pyramidal neurons) become active when animals enter a particular place in the environment , known as the place field. Young CA3 place cells readily remap and shift their representations, while aged CA3 place cells retain their original fields despite changes in the environment (Wilson et al. 2006; Yassa et al. 2011). Next to place cells in the hippocampal CA1 and CA3 subregions, time cells have recently been identified, shown to track the elapsing of time (Macdonald et al. 2011; Shapiro 2011; Mankin et al. 2012). "
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    ABSTRACT: Time-place learning (TPL) offers the possibility to study the functional interaction between cognition and the circadian system with aging. With TPL, animals link biological significant events with the location and the time of day. This what-where-when type of memory provides animals with an experience-based daily schedule. Mice were tested for TPL five times throughout their lifespan and showed (re)learning from below chance level at the age of 4, 7, 12, and 18 mo. In contrast, at the age of 22 mo these mice showed preservation of TPL memory (absence of memory loss), together with deficiencies in the ability to update time-of-day information. Conversely, the majority of untrained (naïve) mice at 17 mo of age were unable to acquire TPL, indicating that training had delayed TPL deficiencies in the mice trained over lifespan. Two out of seven naïve mice, however, compensated for correct performance loss by adapting an alternative learning strategy that is independent of the age-deteriorating circadian system and presumably less cognitively demanding. Together, these data show the age-sensitivity of TPL, and the positive effects of repeated training over a lifetime. In addition, these data shed new light on aging-related loss of behavioral flexibility to update time-of-day information. © 2015 Mulder et al.; Published by Cold Spring Harbor Laboratory Press.
    Learning & memory (Cold Spring Harbor, N.Y.) 05/2015; 22(5):278-288. DOI:10.1101/lm.037440 · 3.66 Impact Factor
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    • "This is the first report of an age-related reduction in memory specificity in hippocampus and the first to use trial-unique stimuli, converging with recent findings in cortical regions for reinstatement at the level of individual items (St-Laurent et al., 2014). Models of hippocampal function specify that it is critical for the pattern separation of distinct memory traces for highly similar events and their later reinstatement by pattern completion (Marr, 1982; O'Reilly and McClelland, 1994; Treves and Rolls, 1994), functions which appear to be compromised in aging (Wilson et al., 2006; Yassa et al., 2011). It is important to note that the group difference in neural memory specificity did not reflect a simple absence of recollection in the older adults: recollective experience was just as likely in this group, and received the same boost from semantic as opposed to phonological processing. "
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    ABSTRACT: The dedifferentiation theory of aging proposes that a reduction in the specificity of neural representations causes declines in complex cognition as people get older, and may reflect a reduction in dopaminergic signaling. The present pharmacological fMRI study investigated episodic memory-related dedifferentiation in young and older adults, and its relation to dopaminergic function, using a randomized placebo-controlled double-blind crossover design with the agonist Bromocriptine (5mg) and the antagonist Sulpiride (400mg). We used multi-voxel pattern analysis to measure memory specificity: the degree to which distributed patterns of activity distinguishing two different task contexts during an encoding phase are reinstated during memory retrieval. As predicted, memory specificity was reduced in older adults in prefrontal cortex and in hippocampus, consistent with an impact of neural dedifferentiation on episodic memory representations. There was also a linear age-dependent dopaminergic modulation of memory specificity in hippocampus reflecting a relative boost to memory specificity on Bromocriptine in older adults whose memory was poorer at baseline, and a relative boost on Sulpiride in older better performers, compared to the young. This differed from generalized effects of both agents on task specificity in the encoding phase. The results demonstrate a link between ageing, dopaminergic function and dedifferentiation in the hippocampus. Copyright © 2015. Published by Elsevier Inc.
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    • "This is in line with models that emphasize the role of PI as a prominent characteristic of memory in aging. Several neurobiological models of aging specifically propose increased PI to be a major factor in hippocampal-dependent aging-related deficits in memory acquisition (e.g., Wilson et al., 2006). Together, the current results show that learning through FM can occur even when the MTL system is severely dysfunctional, but that the MTL system can play a role in preventing retroactive catastrophic forgetting in healthy adults. "
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    ABSTRACT: The human cortex can accommodate overlapping semantic information, such as synonyms, homonyms or overlapping concepts. However, neuronal models of cortical networks predict Catastrophic Interference in conditions of overlapping information, obliterating old associations and sometimes preventing formation of new ones. It has been proposed that Catastrophic Interference in declarative memory is never observed in biological systems because of hippocampal pattern separation of competing associations. Here, we tested neocortical Catastrophic Interference during acquisition of overlapping associations through Fast Mapping; an incidental, exclusion based learning mechanism, that can support hippocampal-independent learning. Young adults acquired picture-label associations, either through explicit encoding or through Fast Mapping and were tested after 24 hours. Overlapping/competing associations were presented either minutes (Early), or 22 hours (Delayed) after learning. Catastrophic Interference was evident only following Fast Mapping, and only in the Delayed competition. In a follow-up experiment, Medial Temporal Lobe (MTL) amnesic patients demonstrated retroactive Catastrophic Interference after the Early competition, despite normal memory for non-interfered Fast Mapping associations. Thus, following Fast Mapping, a biological system demonstrated susceptibility to Catastrophic Interference, as predicted by the neuronal-model. Early retroactive Interference, however, can be prevented by MTL integrity. © 2014 Wiley Periodicals, Inc.
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