Pup exposure differentially enhances foraging ability in primiparous and nulliparous rats☆
Introduction
The female rodent brain undergoes significant changes in response to the varying levels of gonadal hormones accompanying the different stages of the estrus cycle. Initially, these cytoarchitectural modifications were observed in the medial preoptic area (mPOA), a brain region traditionally viewed as an area susceptible to gonadal hormone-induced alterations [1], [2]. Subsequent investigations of the female brain, however, confirmed a relationship between the hippocampus, a brain area that is not typically viewed as playing an integral role in reproductive functioning, and fluctuating levels of gonadal steroids. Specifically, ovariectomized rats experience a reduction in the density of dendritic spines found in CA1 pyramidal neurons, an effect reversed by estrogen replacement [3]. This plasticity in the CA1 spines was shown to be cyclical in nature, evidenced by a 30% decrease in dendritic spine density as the animal progressed from proestrus to estrus (i.e., 24 h period) [4]. Lower levels of estrogen are also associated with decreased CA1 synapse density [5] and decreased multiple synapatic contacts in CA1 presynaptic boutons [6]. Functional changes such as altered electrophysiological recordings in CA1 and CA3 neurons [also accompanied by increased hippocampal brain derived neurotrophic factor (BDNF) immunoreactivity on the day of estrus in this study] [7], an estrogen dependent increase in sensitivity to NMDA receptor input [8], enhancement of LTP in the hippocampus [9], and higher phosphorylated proteins in CA1 dendrites [10] have also been reported. Finally, more new BrdU-labeled cells (likely neurons) have been found in the hippocampus of female rodents in proestrus than in diestrus [11].
Following the establishment of estrogen-induced neuroanatomical and neurophysiological changes, researchers continued their investigations to discern the behavioral relevance of these effects. Because of the hippocampus's confirmed role in learning/memory systems, rats in the various stages of the estrus cycle have been assessed in several types of learning tasks. Although the aforementioned neuroanatomical changes are dramatic, the behavioral data are less clear. Increased arm choice accuracy in the radial arm maze has been observed in rats receiving estradiol via silastic capsules for either 24 h or 30 days prior to maze training, compared to controls [12]. Further, chronic administration of estrogen enhanced performance in win-shift trials and in the radial arm maze following 21 days of hormone administration [13]. Conversely, when researchers have investigated learning abilities within the confines of the natural fluctuations of the gonadal hormones over the estrus cycle, different results have been reported. In one study, no learning impairment was observed in estrus animals (compared to proestrus) when tested in a Morris water maze [14]. In another study, estrus animals performed better than proestrus animals in the Morris water maze, whereas they performed more poorly than proestrus animals in a cue task adapted to the water maze [15]. Finally, water maze performance of meadow voles in male-induced constant behavioral estrus fluctuated in response to estradiol levels; specifically, high estradiol females exhibited longer latencies to the platform [16]. In sum, the only apparent consistency in these behavioral studies has been the inconsistencies associated with the findings.
It is likely that learning performance in rodents at various stages of the estrus cycle is sensitive to many task-related stimuli; for example, proestrus rats perform better in a water maze in warm water whereas estrus rats perform better in cold water [17]. Further, even within the same task, rats in different stages of estrus exhibit different learning strategies, with estrus rats showing a “place” strategy and proestrus rats preferring a “response strategy” [18]. Other experimental variations such as exogenous vs. endogenous sources of estrogen, the use of different species, different tasks (e.g., appetitive vs. escape), and varying durations of estrogen exposure contribute to these diverse findings.
It is also possible that the lack of conclusive findings in the behavioral studies previously described is due to the factor of timing of behavioral tests. When one considers the significant events that typically follow proestrus and estrus in the rat's natural environment (i.e., mate location and selection, copulation, pregnancy and parturition), it is possible that the increase in dendritic spines observed during proestrus may serve to foster the development of the hippocampus so that the female is optimally prepared to meet the demands of her pups [19]. Additionally, the surprising relationship between the hippocampus and the fluctuating levels of gonadal hormones becomes more relevant as the ancillary behaviors necessary for successful maternal behavior are considered (e.g., more efficient foraging, multi-tasking associated with the multiple demands of many pups, enhanced defense from environmental threats). Accordingly, it has been suggested that the hippocampus may alter its optimized computational functions in the various estrus cycles as the demands shift to assure both individual and species survival [20]. Indeed, mate selection, copulation, pregnancy, parturition, and lactation represent a continuum of adaptive neurobiological changes necessary for the proper development and maintenance of offspring [21].
If consideration of natural gonadal hormone fluctuations in the larger context of reproductive experience is important in discerning the accurate nature of hormonal influences in the female, \ consistent effects will likely be revealed when animals are tested following pregnancy, a time consisting of chronic and natural elevations of estrogen (and progesterone). Three decades ago, researchers reported that pregnancy resulted in greater cortical thickness, an effect also found in animals housed in enriched environments [22]. Although these animals were examined the day following parturition, an extended time with the novel sounds, smells, sights and tactile stimulation provided by the pups may have served as further enrichment for the maternal animals. Confirming this notion, it was demonstrated that multiparous and primiparous animals exposed to their pups from 14–21 days performed better in two variations of a spatial foraging task [23]. Additional research has shown enhanced social learning in postpartum female rats [24] and, focusing on alterations during pregnancy, enhanced spatial working memory has been observed during the first and second trimesters of the pregnancy, but not in the third trimester [25]. The number of pregnancies may also influence postpartum learning; research with sheep, for example, suggests that biparous ewes identify their lambs using visual and auditory information after 6 h of mother–young contact whereas primiparous ewes using visual and auditory cues required 24 h to demonstrate a preference for their own offspring [26]. Thus, neurobiological findings in maternal mammals are more consistent than research focusing on the aforementioned short-term hormonal fluctuations. The role of the putative enriched environment (consisting of novel sensory stimuli) provided by the offspring, as well as any learning enhancements provided by the pregnancy itself, may be significant variables involved in learning phenomena.
The present study examined the specific influences of two maternal-related variables (i.e., pregnancy and/or pup exposure) on the female rats' performance in two versions of a foraging task. Primiparous and nulliparous rats, either exposed to pups or no pup stimuli, were used in this study. We hypothesized that the animals naturally allowed to experience both pregnancy and pup exposure would exhibit advantages over animals with only partial involvement with maternal experience.
Section snippets
Animals
Fifty-seven female Sprague Dawley rats (70–80 days of age; Charles River Laboratories) were randomly assigned to the following groups: Primparous plus pups (P+; n = 12); Primiparous minus pups (P−; n = 12); Nulliparous plus pups (N+; n = 12); and Nulliparous minus pups (N−; n = 12). Nine additional females were assigned as donor females to produce and maintain foster pups. Ten males were used for breeding. Initially, all animals were multiply-housed (∼ three rats/rack cage) in a vivarium with a
Spatial DLM task
A 2 × 1 mixed ANOVA (pups × parity × trials) indicated a significant trial effect [F(8,224) = 3.7; p = .000]; specifically, a one-way ANOVA testing the effect of trials on latency scores across all groups indicated a significant effect [F(8,279) = 2.2; p = .025) due to the decreased latencies observed from trial 1 to trial 3 on the third day of testing (122–71 s; p = .03). Although not statistically significant, the latency scores for each group during the challenging first day of testing are provided in Fig. 1
Discussion
The current data suggest that females with both parity and pup experience (i.e., natural mothers) possess enhanced foraging skills in certain components of the spatial, cued, and probe versions of the dry land maze (DLM). Primiparous animals with pups (P+) exhibited faster latencies than primiparous animals without pups (P−) on Trial 6 of the spatial DLM task; additionally, the P+ animals' mean latencies across trials was approximately 30% faster than the remaining groups. The variable of
References (42)
- et al.
Estrogen enhances performance of female rats during acquisition of a radial arm maze
Horm Behav
(1997) - et al.
Estradiol enhances learning and memory in a spatial memory task and some effects levels of a monoaminergic neurotransmitters
Horm Behav
(1998) - et al.
Gonadal hormone levels and spatial learning performance in the Morris water maze in male and female meadow voles, Microtus pennsylvanicus
Horm Behav
(1995) - et al.
Shifts in preferred learning strategy across the estrous cycle in female rats
Horm Behav
(2004) Estrogen-mediated structural and functional synaptic plasticity in the female rat hippocampus
Horm Behav
(1998)- et al.
Brain preparations for maternity—adaptive changes in behavioral and neuroendocrine systems during pregnancy and lactation. An overview
Prog Brain Res
(2001) - et al.
Spatial working memory and hippocampal size across pregnancy in rats
Horm Behav
(2000) - et al.
Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons
Brain Res
(1990) - et al.
Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons
Brain Res
(1992) - et al.
Activity stress induces atrophy of apical dendrites of hippocampal pyramidal neurons in male rats
Physiol Behav
(1998)
Alterations in behavioral and neuroendocrine stress coping strategies in pregnant, parturient, and lactating rats
Prog Brain Res
Single or multiple reproductive experiences attenuate neurobehavioral stress and fear responses in the female rat
Physiol Behav
Region-specific immediate-early gene expression following the administration of corticotropin releasing hormone in virgin and lactating rats
Brain Res
Brain oxytocin: differential inhibition of neuroendocrine stress responses and anxiety-related behavior in virgin, pregnant and lactating rats
Neuroscience
Medial preoptic area and maternal behavior in the female rat
J Comp Physiol Psychol
Neural control of maternal behavior
Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood
J Neurosci
Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons
Neurosci
Estradiol mediates fluctuation in hippocampal synapse density during the estrus cycle in the adult rat
J Neurosci
Estradiol increases the frequency of multiple synapse boutonin proestrus rats
Brain Res
Hippocampal excitability increases during the estrous cycle in the rat: a potential role for brain-derived neurotrophic factor
J Neurosci
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This research was generously supported by a National Institute of Health grant #1-R15-HD37578-01 to CHK and KGL.