Effect Of Maternal Deprivation On Learning And Memory And Synaptic Plasticity In Rats

In mammals, the infant-mother relationship provides an initial stimulus environment that shapes early physiological and cognitive development and social behavior. Early maternal deprivation (ED) has been demonstrated to yield long-term variations in the neurobiology and behavior of the offspring in primates and humans. Owing to their rapid breeding and development, the effects of early experience on adult behavior have been most intensively explored in rodents. However, the extent of effects of early maternal deprivation on learning and memory in rats is not always consistent. In addition, less clear is the effect of the early maternal deprivation on synaptic plasticity in rats. Compared with early maternal deprivation, environmental enrichment (EE) provides more complex inanimate and social interactions. While it is clear that EE enhances learning and memory and synaptic plasticity, little is known whether the effects of early maternal deprivation can be reversed by environmental enrichment. Therefore, by employing behavioral methods, corticosterone determination and in vitro electrophysiology technique, we investigated the effects of early maternal deprivation on learning and memory and synaptic plasticity in Sprague Dawley rats, and explored whether the environmental enrichment can reverse these changes. These results give rise to the mechanisms underling the effect of early maternal deprivation on emotion and behavior in adult rats, which suggest the infant-mother relationship play a crucial part in early physiological and cognitive development. The major findings are showed as follows:1 The effect of early maternal deprivation on body weights in ratsThe body weights of one hour (ED1),three hours (ED3) and six hours (ED6) early maternal deprivation groups were compared with control group respectively. The results showed that compared with controls, ED1 and ED3 rats exhibited similar growth curve. However, ED6 rats exhibited significant reduced body weights and delayed growth. These results suggest that ED6 significantly delays the physiological development in rats.Then three hours was defined as duration of early maternal deprivation during our research, and investigated whether EE can reverse the effects of ED3 on rats. Similar to ED3 rats, the body weights of ED3 & EE rats were comparable with control rats, suggesting that both ED3 and EE have no effect on the physiological development in rats.2 The effect of ED3 on basic behavior and emotional memory in ratsBy employing open field, elevated plus maze, light-dark transition and passive avoidance test, we investigated the effects of ED3 on basic behavior and emotional memory in rats, and explored whether EE could reverse these changes.ED3 rats showed normal locomotor activity, exploratory ability in open field. However, ED3 rats exhibited lower level of anxiety in elevated plus maze and light-dark transition, and impaired fear memory in passive avoidance test. Meanwhile, EE could reverse the low anxiety level caused by ED3,but could not repair the fear memory deficit in ED3 rats. These results imply that both HPA axis and amygdala are affected by ED3, and only abnormal HPA axis can be reversed by EE.3 The effect of ED3 on HPA axis activity in ratsWe compared the plasma corticosterone level in control, ED3 and ED3 & EE rats by enzyme-linked immunosorbent assay (ELISA). There was no significant difference between basal corticosterone level in ED3 and control rats on postnatal day 22 (after ED3).However, consistent with emotional determination, ED3 rats exhibited significance lower stress-induced plasma corticosterone level than control rats, and EE could reverse this trend. These results suggest that downregulation of the HPA axis is the cellular and molecular mechanism of abnormal emotion in ED3 rats, and EE can reverse the low anxiety level by modulating the HPA axis.4 The effect of ED3 on recognition and spatial navigation abilities in ratsIn order to identify whether ED3 have effect on non-amgdala dependent memory, we employed novel object recognition task, social discrimination test and Morris water maze to compare recognition and spatial navigation abilities in the three groups. In the novel object recognition task, there was no significant difference between the three groups.However, ED3 and ED3 & EE rats exhibited enhanced recognition ability in the social discrimination test and improved spatial navigation ability in the Morris water maze. Therefore, our results demonstrated that EE can not influence positive effects on recognition and spatial navigation abilities by ED3.5 The effect of ED3 on synaptic plasticity of hippocampus in ratsBy recording field excitatory postsynaptic potentials (fEPSP) in the Schaffer collateral/CA1 pathway, we compared the basic synaptic transmission function and synaptic plasticity between the three groups. The result from input-output curve showed that postsynaptic AMPA receptors in ED3 and ED3 & EE rats were normal. Furthermore, the theta burst stimulation (TBS) could induce the significant LTP in ED3 and ED3 & EE slices but not in control slices. Consistent with results in the water maze, the present study indicates that early maternal deprivation can facilitate LTP induction. Our research is helpful to understand the close relationship between synaptic plasticity and learning and memory.In conclusion, early maternal deprivation impaired amygdala related fear memory, but enhanced prefrontal cortex-dependent social discrimination ability and hippocampus-dependent spatial reference memory. These results suggest that the inhibition of positive feedback from amygdala and the facilitation of negative feedback from prefrontal cortex and hippocampus are neuroendocrinological mechanism of lower HPA axis responsiveness and lower anxiety level in ED3 rats.