Memory and memory loss in the developing rat

Abstract

The present thesis investigated the nature of infant fear memories in two streams of research: memory expression and memory loss. The first series of experiments examined the neural mechanisms underlying fear expression early in development. It was found that the neural substrates involved in fear expression during infancy were qualitatively different to that in older animals. Specifically, the prelimbic cortex (PL), an important structure for fear expression in adult and juvenile animals was neither activated nor required during fear expression in infant animals (Chapter 2). Fear expression was also PL-independent if rats were trained during infancy but tested as juveniles, suggesting that the animal s age at the time of training determines how the animal responds (Chapter 3). However, if rats were given additional training later in life, then this experience was sufficient to update the original memory, rendering fear expression PL-dependent. Collectively, the findings suggest that the expression of learned fear transitions from a PL-independent to a PL-dependent fear circuit. The theoretical and clinical implications of a PL-independent fear circuit early in life are discussed. The second series of experiments focused on the consequences of memory loss, and specifically, how early life fear learning impacts the neurobiology of later relearning despite forgetting (Chapter 4). While initial acquisition of fear in infant rats was dependent on the activation of N-methyl-D-aspartate receptors (NMDArs), reacquisition of fear following forgetting was NMDAr-independent. Interestingly, the transition to NMDAr-independent relearning was observed whether relearning occurred during adolescence or in adulthood, and whether the original or a novel conditioned stimulus (CS) was used. Importantly though, the transition to NMDAr-independent relearning was contingent on early life learning, as relearning was NMDAr-dependent if rats were merely exposed to the context, CS, or unconditioned stimulus (i.e., footshock) during infancy. Taken together, these results suggest that despite forgetting, some part of the memory trace persists and allows the transition to NMDAr-independent relearning to occur. Overall, the findings from both series of experiments reported in this thesis not only provide novel insights into memory processes early in life but also contribute to our understanding of memory development later in life.