Contextual reminders fail to trigger memory reconsolidation in aged rats and aged humans

There is strong evidence that hippocampal memory returns to a labile state upon reactivation, initiating a reconsolidation process that restabilizes it and allows for its updating. Normal aging is associated with deficits in episodic memory processes. However, the effects of aging on memory reconsolidation and its neural substrate remain largely unknown, and an animal model is lacking. In this study we investigated the effects of aging on context-dependent reconsolidation using an episodic set-learning task in humans and an analogous set-learning spatial task in rats. In both tasks, young and older subjects learned a set of objects (humans) or feeder locations (rats; Set 1) in Context A on Day 1. On Day 2, a different set (Set 2) was learned in either Context A (Reminder condition) or Context B (No Reminder condition). On Day 3, subjects were instructed (humans) or cued (rats) to recall Set 1. Young rats and humans in the Reminder condition falsely recalled significantly more items from Set 2 than those in the No Reminder condition, suggesting that the reminder context triggered a reactivation of Set 1 on Day 2 and allowed the integration of Set 2 items into Set 1. In both species, older subjects displayed a different pattern of results than young subjects. In aged rats, there was no difference between conditions in the level of falsely recalled Set 2 items (intrusions). Older humans in the No Reminder condition made significantly more intrusions than those in the Reminder condition. Follow-up control experiments in aged rats suggested that intrusions in older animals reflected general interference, independent of context manipulations. We conclude that contextual reminders are not sufficient to trigger memory updating in aged rats or aged humans, unlike in younger individuals. Future studies using this animal model should further our understanding of the role of the hippocampus in memory maintenance and updating during normal aging.

[1]  Robert A. Bornstein,et al.  The Wechsler Memory Scale—Revised , 1990 .

[2]  Mark R. Bower,et al.  Sequential-Context-Dependent Hippocampal Activity Is Not Necessary to Learn Sequences with Repeated Elements , 2005, The Journal of Neuroscience.

[3]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[4]  Vincent Hok,et al.  Behavioral / Systems / Cognitive Hippocampal Dynamics Predict Interindividual Cognitive Differences in Rats , 2012 .

[5]  Strengthening a consolidated memory: The key role of the reconsolidation process , 2014, Journal of Physiology-Paris.

[6]  M. N. Rajah,et al.  Group differences in anterior hippocampal volume and in the retrieval of spatial and temporal context memory in healthy young versus older adults , 2010, Neuropsychologia.

[7]  Shauna M. Stark,et al.  Age-related memory deficits linked to circuit-specific disruptions in the hippocampus , 2011, Proceedings of the National Academy of Sciences.

[8]  D. Delis,et al.  The California verbal learning test , 2016 .

[9]  B. Winters,et al.  Older and stronger object memories are selectively destabilized by reactivation in the presence of new information. , 2009, Learning & memory.

[10]  C. Reynolds,et al.  Wechsler memory scale-revised , 1988 .

[11]  Madeleine Verriotis,et al.  Behavioral correlates of the distributed coding of spatial context , 2006, Hippocampus.

[12]  L. Nadel.  The hippocampus and context revisited. , 2008 .

[13]  E. Glisky,et al.  Source memory in older adults: an encoding or retrieval problem? , 2001 .

[14]  E. Glisky,et al.  Do young and older adults rely on different processes in source memory tasks? A neuropsychological study. , 2008, Journal of experimental psychology. Learning, memory, and cognition.

[15]  S. Sara.  Retrieval and reconsolidation: toward a neurobiology of remembering. , 2000, Learning & memory.

[16]  S. Sara,et al.  Reactivation, Retrieval, Replay and Reconsolidation in and Out of Sleep: Connecting the Dots , 2010, Front. Behav. Neurosci..

[17]  Shauna M. Stark,et al.  Pattern separation deficits associated with increased hippocampal CA3 and dentate gyrus activity in nondemented older adults , 2010, Hippocampus.

[18]  JaneR . Taylor,et al.  Molecular mechanisms of memory reconsolidation , 2007, Nature Reviews Neuroscience.

[19]  J. Kwentus,et al.  Modified wisconsin sorting test in elderly normal, depressed and demented patients , 1988 .

[20]  K. Nader,et al.  Cellular and systems mechanisms of memory strength as a constraint on auditory fear reconsolidation , 2009, Nature Neuroscience.

[21]  C. Barnes,et al.  Neural plasticity in the ageing brain , 2006, Nature Reviews Neuroscience.

[22]  Howard Eichenbaum,et al.  Cognitive Aging and the Hippocampus: How Old Rats Represent New Environments , 2004, The Journal of Neuroscience.

[23]  A. Hupbach,et al.  Reconsolidation of episodic memories: a subtle reminder triggers integration of new information. , 2007, Learning & memory.

[24]  Jean-Marc Fellous,et al.  Remaking memories: reconsolidation updates positively motivated spatial memory in rats. , 2012, Learning & memory.

[25]  P. Roullet,et al.  Reactivation with a simple exposure to the experimental environment is sufficient to induce reconsolidation requiring protein synthesis in the hippocampal CA3 region in mice , 2007, Hippocampus.

[26]  J. Hart,et al.  Distinct prefrontal cortex activity associated with item memory and source memory for visual shapes. , 2003, Brain research. Cognitive brain research.

[27]  K. Franklin,et al.  Reconsolidation of a morphine place preference: Impact of the strength and age of memory on disruption by propranolol and midazolam , 2010, Behavioural Brain Research.

[28]  K. Nader,et al.  Memory reconsolidation: an update , 2010, Annals of the New York Academy of Sciences.

[29]  Jean-Marc Fellous,et al.  A connectionist model of context-based memory reconsolidation in the hippocampus: the role of sleep , 2014, BMC Neuroscience.

[30]  J. Wixted.  The psychology and neuroscience of forgetting. , 2004, Annual review of psychology.

[31]  Marcia K. Johnson,et al.  Left prefrontal activation during episodic remembering: an event‐related fMRI study , 1998, Neuroreport.

[32]  Marcia K. Johnson,et al.  Prefrontal Cortex Activity Associated with Source Monitoring in a Working Memory Task , 2004, Journal of Cognitive Neuroscience.

[33]  A. Hupbach,et al.  The dynamics of memory: context-dependent updating. , 2008, Learning & memory.

[34]  A. Hupbach,et al.  Episodic memory reconsolidation: Updating or source confusion? , 2009, Memory.

[35]  Alcino J. Silva,et al.  Memory Reconsolidation and Extinction Have Distinct Temporal and Biochemical Signatures , 2004, The Journal of Neuroscience.

[36]  M. Kindt,et al.  Retrieval per se is not sufficient to trigger reconsolidation of human fear memory , 2012, Neurobiology of Learning and Memory.

[37]  B. McNaughton,et al.  Multistability of cognitive maps in the hippocampus of old rats , 1997, Nature.