Enhancing offspring hypothalamic-pituitary-adrenal (HPA) regulation via systematic novelty exposure: The influence of maternal HPA function

In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother's ability to mount a rapid corticosterone (CORT) response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring hypothalamic-pituitary-adrenal (HPA) regulation. Using a 2 × 2 within-litter design, one half of each litter were exposed to a relatively novel non-home environment for 3-min (Neo_Novel) daily during infancy (PND 1-21) and the other half of the litter remained in the home cage (Neo_Home); we further exposed half of these two groups to early adulthood (PND 54-63) novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting CORT (CORTB) and the ability to mount a large rapid CORT response (CORTE) to the onset of an acute stressor. Assessment of adult offspring's ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring's ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent upon the context of maternal HPA regulation. © 2014 Dinces, Romeo, McEwen and Tang.Link_to_subscribed_fulltex

Social Competitiveness and Plasticity of Neuroendocrine Function in Old Age: Influence of Neonatal Novelty Exposure and Maternal Care Reliability

Early experience is known to have a profound impact on brain and behavioral function later in life. Relatively few studies, however, have examined whether the effects of early experience remain detectable in the aging animal. Here, we examined the effects of neonatal novelty exposure, an early stimulation procedure, on late senescent rats' ability to win in social competition. During the first 3 weeks of life, half of each litter received daily 3-min exposures to a novel environment while the other half stayed in the home cage. At 24 months of age, pairs of rats competed against each other for exclusive access to chocolate rewards. We found that novelty-exposed rats won more rewards than home-staying rats, indicating that early experience exerts a life-long effect on this aspect of social dominance. Furthermore, novelty-exposed but not home-staying rats exhibited habituation of corticosterone release across repeated days of social competition testing, suggesting that early experience permanently enhances plasticity of the stress response system. Finally, we report a surprising finding that across individual rat families, greater effects of neonatal novelty exposure on stress response plasticity were found among families whose dams provided more reliable, instead of a greater total quantity of, maternal care

Neonatal Exposure to Novel Environment Enhances Hippocampal-Dependent Memory Function During Infancy and Adulthood

Early life experience affects behavior and brain mechanisms. Handling rats during the first three weeks in life can slow age-related cognitive decline (as measured by a hippocampal-dependent spatial learning task) and reduce age-related hippocampal neuron loss. It is not clear, however, whether this early environmental influence on learning is selective for old age or is more general, affecting cognitive development during infancy and young adulthood as well. We briefly exposed neonatal rats to a novel non-home environment for 3 min daily during the first three weeks of life (as a component of the handling method). We found that this brief early environmental manipulation resulted in enhanced hippocampal-dependent learning immediately after weaning and that this learning enhancement persisted into adulthood. These results suggest that subtle early life events can affect cognitive development in all developmental stages and that changes in neural mechanisms other than neuron number are likely to mediate the learning enhancement at multiple developmental stages

Effect of long term baclofen treatment on recognition memory and novelty detection

We studied the effect of long term baclofen treatment on recognition memory and novelty detection in rats using a habituation paradigm in an open field setting. Rats pretreated with 3 weeks' daily baclofen injection (0, 2 and 5 mg/kg) were tested in four 10 min sessions (familiarization session and three testing sessions: S1, S2 and S3), with 10-min intersession intervals. During S1, S2 and S3, rats were repeatedly exposed to the same two odor stimuli. During S3, for half of the rats in each treatment group, the spatial locations of the two stimuli were switched (Change) and for the other half the stimuli were replaced in the same locations (No Change). Two habituation scores were measured for each subject: H1 = N1 - N2; H2 = N2 - N3 (N(i) the number of contacts made during S(i)). Baclofen at the highest dose (5 mg/kg) reduced the amount of habituation between S1 and S2 (H1) and increased responses to novel spatial arrangement, measured as the difference between H2 for the No-Change and Change groups. These results suggest a simultaneous impairment of recognition memory and enhancement of spatial novelty detection.Link_to_subscribed_fulltex

Neonatal novelty exposure ameliorates anoxia-induced hyperactivity in the open field

We investigated in an animal model of neonatal anoxia whether effects of oxygen deprivation on emotional reactivity can be reversed by neonatal novelty exposure, a behavioral method, involving daily 3 min away from the home cage for the first 3 weeks of life. Male neonates were exposed to either 100% N 2 gas (Anoxia) or room air (Control) for 25 min on postnatal day 1. Within each of the two treatment conditions, one-half of the neonates were further individually exposed to relatively novel non-home cages for 3 min daily during postnatal days 2-21 (Novel: NAnoxia = 20; NControl = 16), while the other half remained in the home cage (Home: NAnoxia = 19; NControl = 19). Emotional reactivity to an open field was evaluated on postnatal day 25 during four 20-s trials. Among home rats, temporal patterns of open-field activity across multiple trials and initial-trial activity significantly differed between the Anoxia and Control rats. In contrast, these differences were eliminated among the Novel rats. These results show that neonatal novelty exposure, an early-stimulation method that has recently been shown to enhance spatial and social memory, adaptive control of stress response, and hippocampal synaptic plasticity, can also eliminate neonatal anoxia-induced changes in emotional reactivity. These findings suggest that brief and repeated, but mild, changes in the postnatal environment may serve to counteract some of the aversive effects induced by neonatal trauma associated with oxygen deprivation. © 2005 Elsevier B.V. All rights reserved.Link_to_subscribed_fulltex

Neonatal exposure to novelty enhances long-term potentiation in CA1 of the rat hippocampus

Exposing rats to an enriched environment over an extended period of time has been shown to enhance hippocampal long-term potentiation (LTP). Whether such prolonged exposure to environmental manipulation is necessary for LTP enhancement and whether the environmentally induced enhancement can persist long after the cessation of the environmental manipulation remain unknown. Using a novelty exposure procedure modified from the method of neonatal handling, we exposed neonatal rats to a non-home environment for 3 min/day during the first 3 weeks of life. We examined the LTP of both population spikes and excitatory postsynaptic potentials (EPSPs), in vitro, in the CA1 of the hippocampus during adulthood (7-8 and 13-14 months of age). We found that both the LTP of population spikes and the LTP of EPSPs were enhanced among animals who experienced neonatal novelty exposure. These results demonstrate that effective environmental enhancement of LTP can be achieved by as brief and as transient a manipulation as a 3-min/day exposure over the first 3 weeks of life. The resulting enhancement can outlast the environmental manipulation by at least 1 year. © 2002 Wiley-Liss, Inc.Link_to_subscribed_fulltex

Early life environment modulates 'handedness' in rats

Right handedness is one of the most prominent markers of human functional brain asymmetry. Deviation from this norm appears to be associated with certain developmental disorders. While many studies have dealt with the genetic contribution to the determination of handedness, few have examined whether environmental factors that are subtler than forced hand switching can modulate the development of handedness. In this study, we exposed rats to a novel environment for 3 min daily during their first 3 weeks of life and found that their paw preferences during both infancy and adulthood showed a leftward shift compared with the controls. This result suggests that 'handedness' can be modified by rather subtle early environmental manipulation. Since exposure to a novel environment does not involve a direct asymmetric activation of the sensory-motor system underlying paw-use, mechanisms beyond this paw-specific system must exist to mediate the observed modulation of 'handedness'. © 2002 Elsevier Science B.V. All rights reserved.Link_to_subscribed_fulltex