Traces of memory: Reacquisition of fear following forgetting is NMDAr-independent

Abstract

Recent research shows that while initial learning is dependent on N-methyl-D-aspartate receptors (NMDArs), relearning can be NMDAr-independent. In the present study we examined whether this switch also occurs following forgetting. The developing animal exhibits much more rapid rates of forgetting than adults, so infant rats were used. It was found that infant rats required NMDArs to learn fear (Experiment 1), and that this memory was forgotten after 14 d (Experiment 2). Despite forgetting, relearning fear did not require NMDAr activation (Experiment 3), even if it occurred in adulthood (Experiment 5). Importantly, animals only showed NMDAr-independent reacquisition if they had received paired (white noise–shock) training during conditioning and not if they received unpaired presentations of the white noise and shock (Experiment 4). In addition, this transition following forgetting was not stimulus specific as learning about a novel stimulus (i.e., light, Experiment 6) was also NMDAr-independent. However, reacquisition to a novel stimulus was NMDAr-dependent if the original fear memory was retained at the time of retraining (Experiment 7). Taken together, these results demonstrate how fear memories acquired early in life can have a long-lasting impact on later learning, even when they have been apparently forgotten (i.e., they are not expressed in the animal’s overt behavior). Further, they support the idea that while memories may be forgotten, they are not gone.

Ontogeny of memory: An update on 40 years of work on infantile amnesia

“…Traditionally, developmental stages in the rodent were based upon the timing of key structural events such as the brain growth spurt [39,40], but in the context of learning and memory we believe it is more appropriate to align developmental stages with the emergence of specific cognitive functions. Rodents up to P23 have been referred to as 'infants' in previous studies, presumably referring to a range of immaturity other than adolescence [41][42][43][44][45]. However, findings accumulating from the last few decades suggest that the cut-off for the end of infancy should be much earlier than this.…”

“…Further evidence for the existence of a memory trace was provided by Richardson and colleagues, who elegantly demonstrated that fear conditioning during infancy, though rapidly forgotten, impacts the neurobiology of later learning [44]. This work is based on how the acquisition of initial fear learning activates a complex intracellular signalling cascade involving glutamate release, activation of protein kinases (such as MAPK) and protein synthesis [23], and disruption of any part of this pathway can interfere with initial learning.…”

Infantile amnesia: forgotten but not gone

“…The idea that an unexpressed memory trace might have an "implicit" effect on later performance in rodents was recently explored by Li and Richardson (2013). In that study, the effect of a memory acquired during infancy, but then forgotten, on the neurobiological mechanisms mediating future learning experiences was examined.…”

“…This is referred to as a "switch" from NMDAr-dependent acquisition to NMDAr-independent reacquisition. Li and Richardson (2013) explored whether this switch to NMDAr-independent reacquisition still occurred if the original learning had been forgotten. Infant rats were trained at 17 d of age with noise CS-shock US pairings.…”

“…That is, when asked to name an out-of-focus picture that progressively came into focus, all three age groups performed better (i.e., named the picture sooner) with familiar pictures from the storybook than with novel pictures. Findings like these have led some researchers in the field of human memory development to suggest that early memories leave at least a partial trace that continues to influence later functioning despite not being explicitly recalled (e.g., Sroufe et al 1990).The idea that an unexpressed memory trace might have an "implicit" effect on later performance in rodents was recently explored by Li and Richardson (2013). In that study, the effect of a memory acquired during infancy, but then forgotten, on the neurobiological mechanisms mediating future learning experiences was examined.…”