Novelty-induced enhancement in spatial memory: Is infancy a critical period?

Abstract

Development of many psychological functions is known to occur within a limited time window and beyond such a critical period, environmental stimulation has little or no effect. With a split-litter 2 × 2 factorial design in which neonatal and early adulthood novelty exposure were two within-litter factors, we examined whether infancy is a critical period for novelty exposure experience to induce a long-lasting functional enhancement in spatial memory and whether the known enhancement effect induced by early life experience can be further augmented by later adult experience. Spatial memory performance was evaluated in a three-day moving platform Morris water maze task. We found that the animals deprived of novelty exposure during infancy could nevertheless benefit from a delayed adult exposure and that the magnitude of this enhancement was comparable to the enhancement induced by neonatal exposure. This finding indicates that infancy is not a critical period beyond which novelty exposure will have little effect on enhancing spatial memory. Surprisingly, although both neonatal and adult experience alone produced enhancement in spatial memory performance, animals that experienced both neonatal and adult exposures showed no statistically significant difference from those who had none. This finding indicates that the cumulative effect of neonatal and early adulthood experience of novelty is not additive but a result of non-linear interaction and that knowing the effect of a single-stage-intervention does not allow one to predict the final developmental outcome without taking into consideration events occurring before or after.

Introduction

From the early discovery of the imprinting phenomenon [1] to the recent demonstration of switching between attachment and fear during infancy [2], the critical period has been one of the most enduring concepts in developmental psychology and developmental neuroscience [3], [4]. The critical period refers to the period during which exposure to a certain environment is necessary for the development of minimally normal function [5], [6], [7]. This construct has been extensively explored and well established for simple sensory and motor functions as well as for certain higher level functions such as language [8]. However, for many other higher level functions, such as intelligence, general cognitive ability, and social-emotional functions, institutionalized infants with severe impairment could nevertheless “catch up” as a result of adoption [9], [10], [11], [12], [13], [14]. Similarly, in rodents, negative effects of early traumatic experience on spatial learning and memory can be reversed by exposure to the enriched environment treatment during adulthood [15], [16], [17], [18], [19] (For reviews, see [20], [21]). Thus, it appears that for reversing effects of early deprivation on certain higher-level functions, there is no evidence supporting the existence of a critical period.

We have previously shown with replications that neonatal novelty exposure, a procedure consisting of 3 min daily exposures to a non-home environment during the first three postnatal weeks can lead to enhancement in spatial memory as assessed in a working memory version of the Morris water task [22], [23]. The same neonatal treatment also lead to enhanced synaptic plasticity in the CA1 region of the hippocampus [24] and enhanced modulation of such plasticity by the stress hormone corticosterone [25]. Furthermore, this novelty-induced enhancement in synaptic plasticity was preferentially observed in the right but not the left hippocampus [26]. Interestingly, the same neonatal treatment also lead to multiple behavioral expressions of underlying brain asymmetry as indicated by a right hemisphere and left-paw shift in a reach task [27] and a right-hemisphere and right-turn preference in spontaneous movement [28], [29]. Most intriguing is an association found between being a right-turner (right hemisphere dominance) and a better social recognition memory [28], [29].

In the present study, we examined whether infancy is a critical period during and only during which novelty exposure can exert a long-lasting effect on enhancing spatial memory and whether the spatial memory performance is associated with brain asymmetry. In contrast to reversing a previously induced deficit, we considered directly enhancing functionality in the present study. We used a 2 × 2 within-litter factorial design in which siblings within each rat family were divided and assigned to four experimental conditions defined by whether the rat received exposures to a relatively novel non-home environment (N) or stayed only within the home cage (H) during neonatal or early adulthood (Group1: NeoH-AdultH; Group 2: NeoH-AdultN; Group 3: NeoN-AdultH; Group 4: NeoN-AdultN). Using this within-litter design, maternal variables, including maternal separation and separation related stress, pup-pup separations, handling of moms and pups per se, are all controlled for and thus independent from the novelty exposure variable. This is an important feature that distinguishes this neonatal novelty exposure procedure from the so-called neonatal handling procedure [30], [31], which is known to involve multiple confounded factors as listed above. We evaluated 24 h spatial memory performance and one-trial learning in a moving platform Morris water maze task. Specifically, we tested the following hypotheses: (1) when administered during early adulthood, exposures to the novelty associated with a non-home environment can lead to enhancement in spatial memory function; (2) the adult treatment can augment the effect of neonatal treatment in enhancing spatial memory performance; and (3) individual differences in spatial memory performance are associated with differences in behavioral measure of brain asymmetry.