Early life manipulations alter learning and memory in rats

Abstract

Much research shows that early life manipulations have enduring behavioral, neural, and hormonal effects. However, findings of learning and memory performance vary widely across studies. We reviewed studies in which pre-weaning rat pups were exposed to stressors and tested on learning and memory tasks in adulthood. Tasks were classified as aversive conditioning, inhibitory learning, or spatial/relational memory. Variables of duration, type, and timing of neonatal manipulation and sex and strain of animals were examined to determine if any predict enhanced or impaired performance. Brief separations enhanced and prolonged separations impaired performance on spatial/relational tasks. Performance was impaired in aversive conditioning and enhanced in inhibitory learning tasks regardless of manipulation duration. Opposing effects on performance for spatial/relational memory also depended upon timing of manipulation. Enhanced performance was likely if the manipulation occurred during postnatal week 3 but performance was impaired if it was confined to the first two postnatal weeks. Thus, the relationship between early life experiences and adulthood learning and memory performance is multifaceted and decidedly task-dependent.

Fig. 1

Numbers of studies conducted by duration of early life manipulation are presented by duration type (brief vs. prolonged). Brief is defined as <60-min and prolonged is defined as 1-hr or longer. “Other” includes limited nesting, artificial rearing, and corticosterone or CRH administrations, all of which are considered “prolonged: manipulations.

Fig. 2

Numbers of studies reported upon in this review are presented by task and task category. Abbreviations: CtxF=context-induced fear; CueF=cue-induced fear; IA=inhibitory avoidance; FPS=fear-potentiated startle; EBC=eyeblink conditioning; CTA=conditioned taste aversion; LI=latent inhibition; MWM=Morris water maze; RAM=radial arm maze; CM=circular maze; CT= can test; TM=T-maze; YM=Y-maze; SM= Social memory; OR=object recognition; AA=active avoidance.

Fig. 3

Proportion of studies categorized as aversive conditioning, inhibitory learning, or spatial/relational memory tasks that showed enhanced (solid bars) or impaired (open bars) performance by duration of manipulation and task type. Durations were either brief (<60-min) or prolonged (≥1-hr). Duration has opposing effects on performance in spatial memory tasks but did not affect aversive conditioning or inhibitory learning task performance.

Fig. 4

Proportion of studies categorized as aversive conditioning, inhibitory learning, or spatial/relational memory tasks that show enhanced (solid bars) or impaired (open bars) performance by timing of manipulation and task type. Timing refers to manipulations that did not occur during postnatal week 3 (No PN Wk3) or did occur during postnatal week 3 (PN Wk3). Timing has opposing effects on performance in spatial memory tasks but did not affect inhibitory learning task performance. Enhanced aversive conditioning was only seen if the manipulation did not extend into post-natal week 3.

Fig. 5

A schematic to explain the competing effects of duration and timing of postnatal manipulation on performance in spatial/relational memory tasks is presented. Performance on these tasks is enhanced (+) when the duration of the manipulation is short (<1-hr). But, as the duration increases (≤1-hr), performance on the task is impaired (−). When the manipulation is not imposed during postnatal week 3, performance is impaired (−). But, performance is enhanced (+) if the timing of the manipulation includes postnatal week 3.

Fig. 6

A model of how varying the duration and timing of postnatal manipulations may affect amygdala, hippocampus, and prefrontal cortex to respectively alter performance in aversive conditioning, spatial/relational memory tasks, and inhibitory learning is presented. Ovals represent the brain regions of amygdala (A), hippocampus (H), and prefrontal cortex (PFC) and oval size reflects the degree of development of the structure (small = less developed; large = more developed). Environmental factors have the greatest impact if they occur during the cascade of developmental processes and not before or after (Rice and Barone 2000). Thus, the fill of each brain region oval differs depending upon its state of development. Gray-filled ovals reflect that the structure has developed (e.g., amygdala). Open-filled ovals reflect that the structure is not in a developing state (e.g., PFC). The wavy-lined fill of the hippocampus for the two scenarios in which the manipulation is confined to the first two postnatal weeks depicts that this structure is in a developing state. Note that this structure has a gray-fill (depicting that it is developed) for the scenario in which the manipulation extended into postnatal week 3. Arrow sizes depict the degree of effect. The larger arrows from amygdala to hippocampus for the two scenarios in which the manipulation is confined to the first two postnatal weeks reflects the greater input from amygdala to hippocampus that would likely occur due to the differences in their states of development.