Article

Motherhood improves learning and memory: Neural activity in rats is enhanced by pregnancy and the demands of rearing offspring.

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Abstract

The hormones of pregnancy may prepare sites that regulate learning and memory, in much the same way that they stimulate the medial preoptic area to respond with maternal behavior when pups are born. This study investigated this idea by testing multiparous (animals that had given birth and lactated twice) and age-matched nulliparous (virgin) female rats on a 16-day regimen of radial-arm maze tests. On the 1st 6 days, multiparous Ss made significantly more correct choices than nulliparous females. In a 2nd experiment, virgin female rats were assigned to 1 of 3 groups: fosters, maternals, and nulliparous. In the dry-land version of the Morris watermaze, maternal Ss took significantly less time than nulliparous Ss to recall and locate the food reward. No significant differences were observed between foster and maternal rats. These results show that a combination of reproductive and pup experience and stimulation is beneficial to learning and memory in female rats. Findings indicate that hormone-induced modifications to the hippocampus may improve the navigation skills involved in parental resource-gathering behaviors. (PsycINFO Database Record (c) 2012 APA, all rights reserved)

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... These changes likely contribute to the mother's behavioral repertoire, economizing and increasing efficiencies directed at the care, protection, and nurturing of the vulnerable offspring. 1 The mother receives a boost to those behaviors required for both her and her offspring's survival; in exchange, the probability that her genes will survive is enhanced. We have argued that unfortunately, because the male/father may be compromised or not contributory because of the likelihood of competition-related injury, death, or unfaithfulness, the burden has fallen on the nervous systems of the female to care for the vulnerable genetic legacy. ...
... Primiparous (PRIM) and multiparous (MULT) rats showed better performance compared to NULL females in both the 8arm radial maze and the dry land maze (which is analogous to the Morris water maze). 1,2,4 Compared to nonmothers, parous females are more efficient and faster to find the food reward in both types of memory tasks. Further, neuroanatomical analyses have shown relevant structural changes. ...
... Last, memory enhancement is not isolated to pregnancy events alone: rodent models have shown that memory and spatial learning continue postpartum or in foster mothers through sensory stimulation provided by pups (e.g., sights, smells, sounds, suckling, and tactile stimulation). 1,8 Thus, maternal stimuli facilitation of long-term potentiation (LTP) in mothers may underlie some of their behavioral augmentation. ...
... Hippocampus-dependent behavioral change has also been assessed in maternal rats. Multiparous rats perform better than virgins in the radial-arm maze; further, both maternal and pup-sensitized rats exhibited a stronger spatial memory than virgins in a version of the Morris water maze known as the dry land maze (Kinsley et al., 1999). In a competitive spatial foraging task, multiparous rats exhibited shorter latencies to reach food rewards than age-matched primiparous and virgin rats (Love et al., 2005). ...
... injuries were able to move capably after the KA exposure, they were re-exposed to the dry land maze spatial memory task to assess the interruption of previously learned information in these animals. Results confirmed enhanced spatial memory effects previously found in maternal animals in our laboratory (Kinsley et al., 1999). Considering the latency to approach the previously baited well (a measure of memory strength), the saline maternal animals approached the previously baited well significantly faster than all other groups. ...
... Research using the DLM, a dry land adaptation of the Morris Water Maze, has previously indicated that maternal experience enhances spatial memory in rats when compared to nulliparous animals (Kinsley et al., 1999). As previously described rats were initially exposed to a 3 day training period during which the rats became familiar with the apparatus and location of baited wells. ...
Article
The hormones of pregnancy and lactation (e.g., estrogen, progesterone, and oxytocin) have been shown to modulate learning, memory, and the restructuring of brain areas not traditionally associated with maternal behavior. Given the impact of reproductive experience on plasticity of brain areas such as the hippocampus, kainic acid (KA) was used in the current study to induce hippocampal-specific neurotoxic insult in adult multiparous and virgin Long-Evans rats. In Experiment I, Fluoro-Jade B, an indicant of degenerating cells, revealed significant neuronal damage in KA-treated hippocampi at 16 h post-injection in both maternal and virgin rats. In Experiment II, maternal and virgin rats were assessed in spatial and novel object preference tasks to determine the effects of KA on subsequent behavioral and cognitive responses. Twenty-four hours post injection, saline maternal animals exhibited superior memory in a spatial task. Further, maternal saline-injected rats were more similar to maternal KA-injected rats than both the virgin groups. Forty-eight hours following the KA or saline injection, compared to virgins, maternal animals demonstrated enhanced memory in the novel object memory test, regardless of type of injection. Further, neurobiological assessments in Experiment II indicated that virgin KA exposed rats had significantly more glial fibrillary acidic protein (GFAP)-immunoreactivity in the hippocampus, suggesting that they were in an earlier stage of neural recovery compared to maternal animals or, alternatively, may have exhibited more trauma than maternal animals. Together, these data suggest that the previously reported plasticity of the maternal brain may facilitate neural and behavioral recovery from neural insults.
... Concerning neurobiological mechanisms accompanying the acquisition of maternal behavior, transformative events likely begin prior to mating. During the brief time of the estrous cycle when progesterone and estrogen levels peak, dendritic spines emerge on the pyramidal cells of the hippocampus CA1 area, perhaps to facilitate the location of a potential mate or to begin the process of preparing the brain for the increased demands accompanying motherhood [17,18]. Beyond the hippocampus, estrogen receptors are localized throughout the CNS and, when activated, result in rapid effects that are mediated by receptors associated with either the plasma membrane or intracellular signaling cascades [19]. ...
... Initially we investigated spatial memory in two different foraging tasks, a radial arm maze and a dry land maze (a dry land version of the Morris water maze in which animals learn which of eight previously baited wells will remain baited throughout testing trials) [18]. In both studies, the maternal animals exhibited enhanced spatial memory; further, pup-sensitized virgin females also experienced an advantage. ...
... Focusing on neuroplasticity, increased nestin (an intermediate neurofilament expressed during CNS development as well as during restructuring phases of mature neurons [73][74][75]) was observed in the pup exposed virgins, suggesting that pup exposure, in the absence of a pregnant female, alters hippocampal neurons [72,76]. The potential behavioral plasticity observed in the pupexposed males is in agreement with enhanced spatial memory in pupexposed females [18,61], suggesting that the pups may provide a form of enriched environment for parental (and nonparental) rodents. ...
... Therefore, we have examined regions such as the hippocampus and forebrain, which support the display of maternal behaviour. The hippocampus displays significant natural plasticity, both structurally, in terms of significant dendritic spine changes owing to the reproductive state (12)(13)(14)(15)(16)(17)(18) and neurogenetic restructuring (19,20); and Barha et al., 2007;(21, 22, 23), and in functions and behaviours that are tied to its behavioural regulation (i.e. spatial ability) (16,24). ...
... The hippocampus displays significant natural plasticity, both structurally, in terms of significant dendritic spine changes owing to the reproductive state (12)(13)(14)(15)(16)(17)(18) and neurogenetic restructuring (19,20); and Barha et al., 2007;(21, 22, 23), and in functions and behaviours that are tied to its behavioural regulation (i.e. spatial ability) (16,24). ...
... Last, a recent study provides strong evidence for IGF-2 being involved in memory enhancement. Chen et al. (33) demonstrate that, in hippocampal slices, IGF-2 has the ability to enhance longterm potentiation, an effect not dissimilar from the findings of Tomizawa et al. (34), who showed that similar systems underlay the spatial memory improvements that we and others have reported (2,12,13,16,(35)(36)(37)(38)(39). Therefore, the role of IGF-2 in the various memory enhancements reported in mothers represents a fertile area for additional research. ...
Article
In the rat, the change from a virgin/nulliparous female to the maternal animal takes place at many levels. A subtle developmental wave washes over the female nervous system and transforms her from largely self-centred to offspring-directed, from personal care and protection to care of genetically-related offspring, from indifference to ardour. Such change is preceded by substantial and apparently permanent neural alterations, the depth of which results in the maternal brain, and is the basis of the present review. The neuroplasticity of pregnancy, inherent to the female brain and, we believe, representative of the full expression of the female nervous system's capacity, is a result of significant hormonal and other neurochemical actions. It results in the striking brain changes that are associated with, and necessary for, successful reproduction. We discuss some of these changes and their ramifications. Collectively, they represent the culmination of mammalian evolution and have led to the development of the social brain characteristic of higher orders of mammal, including the human. We also examine different facets of the maternal brain, beginning with a review of the genes involved in maternal behaviour, and in the subsequent 'expression' of the maternal brain. We next discuss olfaction and the manner in which this major sense draws from the rich sensory milieu of the mother to regulate and support maternal behaviour. Last, we discuss the 'whys' of maternal behaviour, a theoretical foray into the reasons for such substantial maternal brain alterations. We focus on the male's potential role as the raison d'etre for the manifest alterations in his mate's brain. In the end, it is clear that the female brain undergoes a significant reorganisation en route to motherhood, the results of which are deep and enduring.
... For example, efficient foraging, a behavior dependent on spatial memory, reduces the maternal female's time away from her vulnerable pups and minimizes expended energy during the metabolically challenging period of lactation. Indeed, female rats tested in foraging tasks soon after parturition and lactation exhibit enhanced spatial memory for food rewards (Kinsley et al., 1999). In addition to modifications in foraging behaviors, maternal females exhibit enhanced exploratory behaviors and increased aggression, behaviors also important for meeting postpartum challenges (Svare, 1990;Wartella et al., 2003). ...
... Focusing on behavior, when spatial memory was tested in pregnant rats during the first two trimesters, the pregnant rats outperformed the nonpregnant rats (Galea et al., 2000). In addition to the previously mentioned study showing enhanced spatial memory in two spatial tasks (e.g., radial arm maze and a dry land maze) in parous rats (Kinsley et al., 1999), postpartum rats performed better than NULL subjects in social learning tasks that were independent of pup-or maternal-related cues (Fleming, Kuchera, Lee, & Winocur, 1994). ...
... The dry land maze (DLM; 1.2-m diameter [after Kesner, Dakis, & Bolland, 1993, and similar to that used in Kinsley et al., 1999]) was constructed of a masonite board wall 41 cm high and a linoleum floor that was covered with corncob bedding during testing. Eight translucent wells (2.5-cm diameter) were screwed to the floor of the maze in equidistant increments around the perimeter of the maze (see Figure 1). ...
Article
Full-text available
From 5 to 22 months of age, cognitive and emotional responses of nulliparous, primiparous, and multiparous rats were assessed using a dry land maze (DLM) and an elevated plus-maze (EPM) at 4-month intervals. Parous rats exhibited improved spatial memory in the probe and competitive versions of the DLM, and more exploration in the EPM and a novel stimulus test relative to nulliparous females. The nulliparous females, however, outperformed parous rats during the DLM visual cue test at 17 months of age. At 23 months, no differences in stressed corticosterone levels or Golgi-stained hippocampal neurons were observed. Thus, cognitive and emotional modifications were observed in parous rats; the neurobiological mechanisms for these enduring effects, however, remain to be identified.
... For sustenance or subsistence, for example, and due to increased energy demands, maternal rats benefit from being more efficient foragers; additionally, less time spent away from the nest likely translates directly into decreased vulnerability for the helpless and altricial pups. Accordingly, maternal rats exhibit enhanced foraging/spatial ability in an 8-arm radial maze, and in an analog of the Morris Water Maze (viz. the dry land maze; Kesner & Dakis, 1995) in which they learn the location of a baited food well ( Bodensteiner, Cain, Ray, & Hamula, 2005;Gatewood et al., 2005;Kinsley et al., 1999;Love et al., 2005;Pawluski, Walker, & Galea, 2006). Enhanced (and accurate) processing of the social surround, weighing threat against maternal aims is another ancillary maternal behavior central to successful parenting; postpartum rats performed better than NULL subjects in social learning tasks that were independent of pup or maternal cues ( Fleming, Kuchera, Lee, & Winocur, 1994). ...
... As mentioned, these neural effects appear to translate into improvements in learning and memory. We have reported that pregnancy, and/or its attendant pup stimuli, facilitates spatial learning and memory in the rat ( Kinsley et al., 1999). Our data and others' have demonstrated that reproductive experience enhances spatial learning and foraging behavior in mothers compared to non-mothers. ...
... How does this happen and in what sequence? Hormone-induced modifications in maternal behaviorrelevant sites such as the mPOA, and the hippocampus may facilitate the requisite behavioral improvements involved in pup-directed care and resource-gathering behaviors in which the female is engaged ( Kinsley et al., 1999). As Jacobs, Gaulin, Sherry, and Hoffman (1990) have demonstrated, changes in the volume of the hippocampus (in their particular case, in males during the breeding season) positively correlate with increases in home range size, the distance traversed by the animal. ...
Article
Maternal behavior is multidimensional, encompassing many facets beyond the direct care of the young. Formerly unfamiliar activities are required of the mother. These include behaviors such as retrieving, grouping, crouching-over, and licking young, and protecting them against predators, together with enhancements in other behaviors, such as nest building, foraging, and aggression (inter/intra-species, predatory, etc.). When caring for young, the mother must strike a seemingly lose-lose bargain: leave the relative safety of the nest and her helpless offspring to forage for food and resources where predators await both mother and her vulnerable young, or remain entrenched and safe, thereby ensuring a slow and inexorable fate. Two predictions thus arise from this maternal cost-benefit ratio: first, there may be enhancements in behaviors on which the female relies, for example, predation and spatial ability, used for acquiring food and resources and for navigating her environment. Second, there may be reductions in the fear and anxiety inherent to the decision to leave the nest and to forage in an unforgiving environment where encounters with predators or reluctant/resistant prey await. There is overwhelming support for both hypotheses, with improvements in learning and memory accompanied by a diminution in stress responses and anxiety. The current review will examine the background for the phenomenon that is the maternal brain, and recent relevant data. In sum, the data indicate a remarkable set of changes that take place in the maternal (and, to a lesser extent, the paternal), brain, arguably, for the natural, simple but singular experience of reproduction.
... Tomizawa et al. (33) have reported that the neuropeptide oxytocin plays a significant role in the enhancements in spatial learning that we have observed (2). Briefly, these researchers blocked oxytocin in parous female mice, or infused oxytocin in virgin females, regulating spatial learning, with antagonism in the former, and facilitation in the latter. ...
... Our data and that of others have demonstrated that reproductive expe-rience enhances spatial learning and foraging behaviour in mothers compared to non-mothers. Since the publication of our 1999 paper demonstrating parity-enhanced spatial memory in the female rat (2), there have been numerous replications and extensions of the phenomenon, including much work from disparate laboratories. Tomizawa et al. (33) extended the work to mice and convincingly implicated oxytocin and hippocampal MAPK activity as regulators. ...
... Additional research has replicated and extended the effect, showing that no effect is present during pregnancy, but that later enhancements do occur, again favouring reference memory (83). Recent work in our laboratories has reported that the offspring play a significant role in the memory enhancements, as suggested by our original paper (2,3). As discussed in the next section, we have recently reported that there are likewise enhancements in spatial memory that include relationships to ageing and the development of anxiety responses, which we would like to characterise further (84)(85)(86). ...
Article
Full-text available
As a female transitions into motherhood, many neurobiological adaptations are required to meet the demands presented by her offspring. In addition to the traditional maternal responses (e.g. crouching, nursing, retrieving, grooming), our laboratories have observed several behavioural modifications accompanying parity, especially in the areas of foraging and emotional resilience. Additionally, brain modifications have been observed in the hippocampus and amygdala, providing support for neural plasticity extending beyond the expected hypothalamic alterations. Interestingly, we have observed parenting-induced neuroplasticity to persist into late adulthood, even providing protection against age-related brain and memory deficits. Although the majority of work on the parental brain has been conducted on females, preliminary research suggests similar changes in the biparental male California deer mouse. Taken together, research suggests that the parental brain is dynamic and changeable as it undergoes diverse and, in some cases, long-lasting, modifications to facilitate the production and care of offspring.
... As pregnancy progresses, the female is literally transformed from an organism that actively avoided offspring-related signals, to one highly motivated by those same cues to build nests, retrieve, group, groom, crouch-over, and care for young (Numan and Insel, 2003). Ancillary responses such as reference memory, spatial learning, foraging, and boldness improve in mothers compared to NULLs (Kinsley et al., 1999;Pawluski et al., 2006a,b). Such modifications arise early and are persistent, with neural benefits that last well into senescence (Gatewood et al., 2005). ...
... The improvements come at a crucial time; for the mother, time spent foraging is time removed from vulnerable young. Increased efficiencies, such as those associated with resource acquisition, translate into a lower cost:benefit ratio, better survivability odds for both mother and young, and maximized parental investment (Kinsley et al., 1999;Gatewood et al., 2005). Further, that the behavioral enhancements come at a time, too, when the mother is physically larger and more unwieldy compared to her NULL counterpart (especially during mid-late pregnancy), suggests a (likely) set of strong compensatory motor mechanisms that provide a significant boost to the female's behavioral repertoire. ...
Article
Full-text available
In previous laboratory investigations, we have identified enhanced cognition and reduced stress in parous rats, which are likely adaptations in mothers needing to efficiently exploit resources to maintain, protect and provision their immature offspring. Here, in a series of seven behavioral tests on rats, we examined a natural interface between cognition and resource gathering: predation. Experiment 1 compared predatory behavior (toward crickets) in age-matched nulliparous (NULL) and postpartum lactating mothers (LACT), revealing a highly significant enhancement of predation in LACT females (mean=~65sec. in LACTs, v. ~. 270sec. in NULLs). Experiment 2 examined the possibility that LACTs, given their increased metabolic rate, were hungrier, and thus more motivated to hunt; doubling the length of time of food deprivation in NULLs did not decrease their predatory latencies. Experiments 3-5, which examined sensory regulation of the effect, indicated that olfaction (anosmia), audition (blockade with white noise), and somatosensation (trimming the vibrissae) appear to play little role in the behavioral enhancement observed in the LACTs; Experiment 6 examined the possibility that visual augmentations may facilitate the improvements in predation; testing LACTs in a 0-lux environment eliminated the behavioral advantage (increasing their latencies from ~65sec. to ~212sec.), which suggests that temporary augmentation to the visual system may be important, and hormone-neural alterations therein a likely candidate for further study. In contrast, testing NULLS in the 0-lux environment had the opposite effect, reducing their latency to catch the cricket (from ~270sec. to ~200sec.). Finally, Experiment 7 examined the development of predatory behavior in Early-pregnant (PREG), Mid-PREG, and Late- PREG females. Here, we observed a significant enhancement of predation in Mid-PREG and Late-PREG females - at a time when maternity-associated bodily changes would be expected to diminish predation ability - relative to NULLs. Therefore, as with the increasing reports of enhancements to the maternal brain, it is apparent that meaningful behavioral adaptations occur that likewise promote the survival of the mother and her infants at a crucial stage of their lives.
... While it is accepted that pregnancy can have long-lasting organizing effects on the neural circuits underlying maternal behaviour (the 'maternal brain'), the specific nature and extent of these effects remain poorly understood [39][40][41][42]. Moreover, the fact that mothers are the primary caretakers in most mammal species (and obviously in most rodent laboratory models) has biased most investigations towards motherhood rather than fatherhood or other types of allo-maternal investment [43,44]. ...
Article
Neurobiological changes affecting new mothers are known to support the development of the mother-infant relationship (the 'maternal brain'). However, which aspects of parenting are actually mother-specific and which rely on general cognitive abilities remains debated. For example, refuting earlier findings, a recent study demonstrated that fathers identify their own baby from their cries just as well as mothers. Here we show that this performance is independent not only of sex, but also of parenthood status. We found that mothers' ability to recognize their newborn from their cries increased rapidly within few days postpartum, with highly multiparous mothers performing better. However, both male and female non-parents could similarly recognize an assigned baby, even after a very short exposure. As in mothers, both the initial amount of experimental exposure to the baby's cries (learning opportunity) and prior experience of caring for infants (auditory expertise) affected participants' performance. We thus suggest that, rather than being female-specific or motherhood-dependent, the ability to recognize a baby from their cries derives from general auditory and learning skills. By being available to non-parents of both sexes, it may contribute to the caregiving flexibility required for efficient cooperative breeding in humans.
... It is interesting to speculate that the coordinated activation of hippocampal regions in PUP animals reflects learning of new colony members and is consistent with the increase in cell proliferation observed following pup exposure in prairie voles and fatherhood in male California mice, both species that exhibit biparental care ( Ruscio et al., 2008;Hyer et al., 2016). Alternatively, this could be related to spatial memory required for returning pups to their nest as seen in female rats ( Kinsley et al., 1999). In addition to paradigm-specific patterns of correlated activity, we also report paradigm-specific effects on c-Fos expression in individual brain regions. ...
Article
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The social decision-making network (SDMN) is a conserved neural circuit that modulates a range of social behaviors via context-specific patterns of activation that may be controlled in part by oxytocinergic signaling. We have previously characterized oxytocin’s (OT) influence on prosociality in the naked mole-rat, a eusocial mammalian species, and its altered neural distribution between animals of differing social status. Here, we asked two questions: (1) do patterns of activation in the SDMN vary by social context and (2) is functional connectivity of the SDMN altered by OT manipulation? Adult subordinate naked mole-rats were exposed to one of three types of stimuli (three behavioral paradigms: familiar adult conspecific, unfamiliar adult conspecific, or familiar pups) while manipulating OT (three manipulations: saline, OT, or OT antagonist). Immediate early gene c-Fos activity was quantified using immunohistochemistry across SDMN regions. Network analyses indicated that the SDMN is conserved in naked mole-rats and functions in a context-dependent manner. Specific brain regions were recruited with each behavioral paradigm suggesting a role for the nucleus accumbens in social valence and sociosexual interaction, the prefrontal cortex in assessing/establishing social dominance, and the hippocampus in pup recognition. Furthermore, while OT manipulation was generally disruptive to coordinated neural activity, the specific effects were context-dependent supporting the hypothesis that oxytocinergic signaling promotes context appropriate social behaviors by modulating co-ordinated activity of the SDMN.
... The authors also demonstrated that this induction was mediated by the activation of the MAPK cascade and phosphorylation of cyclic AMP-responsive element binding protein (CREB), suggesting that OXT induced neuronal plasticity in the hippocampus is transcription-dependent. In an attempt to correlate these findings with behavior, the authors demonstrated that ICV administration of OXT in virgin mice improved long-term spatial learning, a result that aligned with a previous discovery showing that spatial memory is enhanced during pregnancy, delivery and lactation, situations when OXT levels are substantially high (Kinsley et al., 1999). Similarly, Lin et al. (2012) endogenous OXT contributes to the maintenance of late but not early phase LTP, which was induced by subthreshold stimulation. ...
Article
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The neuropeptide oxytocin (OXT) is a crucial mediator of parturition and milk ejection and a major modulator of various social behaviors, including social recognition, aggression and parenting. In the past decade, there has been significant excitement around the possible use of OXT to treat behavioral deficits in neurodevelopmental disorders, including autism spectrum disorder (ASD). Yet, despite the fast move to clinical trials with OXT, little attention has been paid to the possibility that the OXT system in the brain is perturbed in these disorders and to what extent such perturbations may contribute to social behavior deficits. Large-scale whole-exome sequencing studies in subjects with ASD, along with biochemical and electrophysiological studies in animal models of the disorder, indicate several risk genes that play an essential role in brain synapses, suggesting that deficits in synaptic activity and plasticity underlie the pathophysiology in a considerable portion of these cases. OXT has been repeatedly shown, both in vitro and in vivo, to modify synaptic properties and plasticity and to modulate neural activity in circuits that regulate social behavior. Together, these findings led us to hypothesize that failure of the OXT system during early development, as a direct or indirect consequence of genetic mutations, may impact social behavior by altering synaptic activity and plasticity. In this article, we review the evidence that support our hypothesis.
... Given that parturition and lactation can enhance spatial cognition in female rodents (e.g. Kinsley et al., 1999), it would be of particular interest to test for effects of motherhood on performance of different types of spatial tasks. For example, path integration (the ability to update spatial position relative to a starting point) relies on the same movementgenerated input and neural substrates (see below) as the routebased task used here, but also requires flexibility in the formation of a cognitive map. ...
Article
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Efficient navigation is a critical component of fitness for most animals. While most species use a combination of allocentric (external) and egocentric (internal) cues to navigate through their environment, subterranean environments present a unique challenge in that visually mediated allocentric cues are unavailable. The relationship between egocentric spatial cognition and species differences in ecology is surprisingly understudied. We used a maze-learning task to test for differences in egocentric navigation between two closely related species of mice, the eastern house mouse, Mus musculus musculus, and the mound-building mouse, M. spicilegus. The two species are sympatric in Eastern Europe and overlap in summer habitat use but differ dramatically in winter space use: whereas house mice occupy anthropogenic structures, mound-building mice survive the winter underground in intricate burrow systems. Given species differences in burrowing ecology, we predicted that M. spicilegus would learn the maze significantly faster than M. m. musculus when tested in complete darkness, a condition that eliminated allocentric spatial information and served as a proxy for the subterranean environment. We found strong support for this prediction. In contrast, the two species performed equally well when different mice were tested in the same maze with lights on. This context-specific species difference in spatial cognition suggests that enhanced egocentric navigation in M. spicilegus is an adaptation to the burrow systems on which the over-winter survival of young mound-building mice depends. The results of this study highlight the importance of ecological adaptations to the evolution of cognitive traits.
... Yet, the transition from nulliparous to parous female involves substantial, likely permanent, alterations to both brain and behavior. These changes are related to the simple recognition that a new set of activities emerge in the new mother, that include both behaviors directly related to pup care and maintenance (the socalled maternal behavior), and others that are ancillary to maternal behavior and allow the mother to be efficient in her search for resources (Kinsley et al., 1999;Lambert et al., 2005). ...
Chapter
We review mammalian maternal behavior, its hormonal regulation, and the neurobiology involved in the onset and offset of specific behavioral patterns. We introduce topics that have flourished recently, e.g., the impact of maternal behavior on the maternal brain. We discuss neuroanatomical changes occurring in the ‘experienced’ mother's brain that translate into more efficient behavior and may underlie enhanced cognition and reduced fear and anxiety. We draw attention to little-explored topics, e.g., timing and the use of maternal behavior as an animal model for exploring specific aspects of neuropsychiatric disorders such as the exaggerated expression of stereotyped motor patterns.
... Although sex differences exist in many motivated behaviors, the lack of sex differences in this paradigm is likely due to the fact that basic flexibility in foraging strategy is adaptive in both males and females. However, although no sex differences in this behavioral paradigm exist in adult virgin rats, females caring for offspring may develop a preference for the optimal choice more rapidly than males and nulliparous females, since maternal females must forage for their pups in addition to themselves (Kinsley et al., 1999;Love et al., 2005). ...
Article
Being able identify decreases in resource availability and alter motivated behavior accordingly is evolutionarily adaptive. Additionally, the neurobiological mechanisms that facilitate these basic foraging skills in animals are thought to be utilized in other forms of goal directed cognition in humans. To study how the brain mediates such behaviors, we adapt an operant behavioral task in which laboratory rats can earn food rewards from two distinct levers. We find that when one lever is extinguished, while the other lever continues to be reinforced, both male and female rats quickly identify this contingency change and develop a choice preference for the rewarded lever. Previous electrophysiology studies of putative midbrain dopamine (DA) neurons have revealed brief pauses in neuronal activity when an expected reward is omitted, which is thought to briefly decrease DA transmission in terminal regions, such as the nucleus accumbens (NAc). Additionally, decreases in DA transmission have been hypothesized to be signaled preferentially through D2 receptors. Other studies, however, have proposed that extra-cellular DA levels over longer periods of time may play a role in motivation and behavioral flexibility. To test these hypotheses, we employ one-minute sampling microdialysis and fast-scan cyclic voltammetry (FSCV) in the NAc. Microdialysis experiments reveal an increase in DA concentration, lasting multiple minutes, following the omission of an expected rewarded. These increases in DA concentration correlate to observed increases in motivational vigor and exploratory behaviors. In contrast, FSCV reveals brief decreases in DA transmission when the expected reward is omitted, consistent with previous electrophysiology studies. Furthermore, holding D2 receptor tone, through site-specific microinfusion of a D2-like agonist into the NAc, attenuates the behavioral preference for the rewarded option. Together, these experiments reveal dynamic changes in DA transmission over multiple time scales when an expected reward is omitted. Tonic increases in DA concentration may motivate the animal to employ alternate behavioral strategies, while the phasic decreases are likely involved in redirecting choice behavior away from the non-rewarded option. This series of experiments provides novel insight into the complex relationships between DA transmission and motivated behavior during negative changes in reward availability.
... Yet, the transition from nulliparous to parous female involves substantial, likely permanent, alterations to both brain and behavior. These changes are related to the simple recognition that a new set of activities emerge in the new mother, that include both behaviors directly related to pup care and maintenance (the socalled maternal behavior), and others that are ancillary to maternal behavior and allow the mother to be efficient in her search for resources (Kinsley et al., 1999;Lambert et al., 2005). ...
Article
Jay Rosenblatt effectively promoted research on rabbit maternal behavior through his interaction with colleagues in Mexico. Here we review the activities of pregnant and lactating rabbits (Oryctolagus cuniculus) , their neuro-hormonal regulation, and the synchronization of behavior between mother and kits. Changing concentrations of estradiol, progesterone, and prolactin throughout gestation regulate nest-building (digging, straw-carrying, fur-pulling) and prime the mother's brain to respond to the newborn. Nursing is the only mother-young contact throughout lactation. It happens once/day, inside the nest, with ca. 24 hr periodicity, and lasts around three minutes. Periodicity and duration of nursing depend on a threshold of suckling as procedures reducing the amount of nipple stimulation interfere with the temporal aspects of nursing, though not with the doe's maternal motivation. Synchronization between mother and kits, critical for nursing, relies on: a) the production of pheromonal cues which guide the young to the mother's nipples for suckling; b) an endogenous circadian rhythm of anticipatory activity in the young, present since birth. Milk intake entrains the kits' locomotor behavior, corticosterone secretion, and the activity of several brain structures. Sibling interactions within the huddle, largely determined by body mass at birth, are important for: a) maintaining body temperature; b) ensuring normal neuromotor and social development.. Suckling maintains nursing behavior past the period of abundant milk production but abrupt and efficient weaning occurs in concurrently pregnant-lactating does by unknown factors. female rabbits have evolved a reproductive strategy largely dissociating maternal care from maternal presence, whose multifactorial regulation warrants future investigations. Copyright © 2015. Published by Elsevier Inc.
... These parity-related organizational effects are wide ranging and include alterations in stress and anxiety behavior [161,162], as well as enhanced immediate and long-term spatial learning [163]. Interestingly, nulliparous females who were induced to show maternal behavior by exposure to foster pups learned a spatial task as quickly as reproductively experienced rats, suggesting that the act of caring for young may be in itself sufficient in inducing these longterm changes [164]. ...
Article
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Studies in both rodents and humans have made much progress in shedding light on how fluctuations in ovarian hormones can affect memory in women across the lifespan. Specifically, advances in neuroscience have identified multiple memory systems that are each mediated by different brain areas. Two memory systems used to navigate an environment are 'place' and 'response' memory. They are defined as either using an allocentric strategy: using a spatial or cognitive map of the surroundings, or an egocentric strategy: using habitual-turns/ movements, respectively. Studies in neuroendocrinology have shown that estrogen levels can bias a female to use one memory system over another to solve a task, such that high estrogen levels are associated with using place memory and low levels with using response memory. Furthermore, recent advances in identifying and localizing estrogen receptors in the rodent brain are uncovering which brain regions are affected by estrogen and providing insight into how hormonal fluctuations during the menstrual cycle, pregnancy, and menopause might affect which memory system is facilitated or impaired in women at different life stages. These studies can help point the way to improving cognitive health in women.
... Several studies have found that maternal experience elicited changes in female mammals' nonreproductive behaviour including fearfulness, sociality or cognitive skills independently of age (Agrati et al. 2008;reviewed in Macbeth & Luine 2010). For instance, parity increases rats' aggressiveness, exploration, general activity and cognitive skills, and reduces their emotional reactivity and fearfulness (Svare 1990;Kinsley et al. 1999;Wartella et al. 2003;Love et al. 2005) as in ewes (Viérin & Bouissou 2002). To our knowledge, the influence of maternal experience on fearfulness and sociality has never been investigated in birds. ...
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Brood care can improve with experience, and experience under natural conditions increases with age. We aimed to evaluate the relative effect of experience by comparing experienced and inexperienced females of the same age under controlled conditions. Using 18 experienced (XP) and 22 inexperienced (NXP) female Japanese quail, Coturnix coturnix japonica. of the same age, we monitored maternal behaviour towards foster chicks. We evaluated the social and emotional reactivity of these females before the breeding period and of the fostered chicks after separation from their mothers. Thus, we determined both how maternal experience affects adult females' nonmaternal behaviour and how potential differences in their maternal behaviour affect chicks' behavioural development. We found that although previous breeding experience per se did not influence either their general fearfulness or their sociality, it did influence the way females coped with novelty. Although most of the maternal care variables did not differ significantly between XP and NXP females, we found several differences, mainly concerning first-time female breeders' more abusive behaviour during the first few days of the breeding period. We suggest that these differences in care are related more to inexperienced females' higher neophobia than to an improvement in the quality of care with experience. In tests, chicks showed differences similar to those of their mothers: chicks brooded by inexperienced females reacted more to novelty than chicks brooded by experienced females. We consider this result to be a case of nongenomic maternal transmission.
... The lack of sex differences in this paradigm is not surprising as flexibility in foraging strategy is adaptive in both males and females. However, although no sex differences in this behavioral paradigm exist in adult virgin rats, females caring for offspring may develop a preference for the optimal choice more rapidly than males and nulliparous females, as maternal females must forage for their pups in addition to themselves (Kinsley et al., 1999;Love et al., 2005). ...
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To survive in a dynamic environment, animals must identify changes in resource availability and rapidly apply adaptive strategies to obtain resources that promote survival. We have utilised a behavioral paradigm to assess differences in foraging strategy when resource (reward) availability unexpectedly changes. When reward magnitude was reduced by 50% (receive one reward pellet instead of two), male and female rats developed a preference for the optimal choice by the second session. However, when an expected reward was omitted (receive no reward pellets instead of one), subjects displayed a robust preference for the optimal choice during the very first session. Previous research shows that, when an expected reward is omitted, dopamine neurons phasically decrease their firing rate, which is hypothesised to decrease dopamine release preferentially affecting D2-like receptors. As robust changes in behavioral preference were specific to reward omission, we tested this hypothesis and the functional role of D1- and D2-like receptors in the nucleus accumbens in mediating the rapid development of a behavioral preference for the rewarded option during reward omission in male rats. Blockade of both receptor types had no effect on this behavior; however, holding D2-like, but not D1-like, receptor tone via infusion of dopamine receptor agonists prevented the development of the preference for the rewarded option during reward omission. These results demonstrate that avoiding an outcome that has been tagged with aversive motivational properties is facilitated through decreased dopamine transmission and subsequent functional disruption of D2-like, but not D1-like, receptor tone in the nucleus accumbens.
... The concentration of pregnenolone, a progesterone precursor, in the hippocampus is inversely correlated with impairment of memory tasks in rats and a temporary improvement of performance was obtained with pregnenolone administration 16 . Progesterone is particularly abundant in pregnancy, and pregnancy has been found to improve learning and memory in rats 17 although these data could not be replicated in humans 18 . One possible explanation of these controversial ®ndings could be that the links between pregnancy and memory are, once again, multifactorial, particularly in humans and there may be several intervening factors, that may in¯uence the recollection of facts, other than hormones. ...
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To investigate the effect of progesterone on cognitive function, mood, sleep quality and libido when added to oestrogen in sequential combined hormonal replacement therapy regimens. Observational study over three hormonal replacement therapy cycles. Menopause Centre of Ospedale Maternità, Bologna, Italy. Twenty-three postmenopausal women with an average of 70 months of amenorrhoea (range 12 to 234 months) on different sequential combined hormonal replacement therapy regimen for an average of 15 months (range 3-48) months. Psychological testing for memory, mood, sleep quality and libido during the oestrogen only part of the cycle compared with the oestrogen-progestogen part of the cycle. Twenty women completed the six visits of the trial. The addition of progestogens to oestrogen appeared to benefit memory (P < 0.01) but worsened mood (P < 0.005). There was no evidence of change in other parameters such as sleep quality or libido. The addition of progestogens improved memory above what was obtained with oestrogen alone. This effect did not depend on an improvement of mood since the latter worsened during the progestogenic phase of an hormonal replacement therapy cycle. Progestogen added to oestrogen did not significantly influence sleep or libido.
... Furthermore, the experience of pregnancy, lactation, and pup exposure appears to play a pivotal role in the alterations of female brain and behavior. In fact, it has been argued that these plastic and adaptive changes are the hallmark of the female brain, as they prepare females to care for an expensive metabolic and genetic investment ( Kinsley et al., 1999;Keyser-Marcus et al., 2001). ...
Article
Reproductive experience (RE), i.e. pregnancy and lactation, induces physiological changes in mammals. Recent data show that neuroimmune interactions are modulated by a diversity of events involving neurotransmitters and neuropeptides. These molecules, particularly dopamine (DA), were reported to mediate the relevant cross talk between immune and neuroendocrine systems. Moreover, DA-mediated regulation of leukocyte function is a reasonable approach to investigate the DA-operated regulatory switch for immune-competent cells, such as macrophages. Therefore, the goals of the present study were to determine the effects of RE on: (1) dopaminergic function through hypothalamic levels of DA, dihydroxyphenylacetic acid (DOPAC), homovanilic acid (HVA), serotonin (5-HT), and 5-hydroxyindole acetic acid (5-HIAA); (2) basal levels of circulating prolactin (PRL); and (3) activity of peritoneal macrophage (phagocytosis and oxidative burst). A total of 16 adult (200-250 g) female Wistar rats were used, divided in two groups: nulliparous and primiparous. Approximately 2-3 weeks after weaning pups from the primiparous group, both groups of rats were tested. The findings indicate that: (1) DOPAC concentrations, DOPAC/DA and HVA+DOPAC/DA ratios decreased in primiparous rats as compared to virgin rats, (2) primiparous rats showed significantly lower serum PRL levels, and (3) phorbol miristate acetate (PMA)-induced oxidative burst was decreased in peritoneal macrophage from primiparous rats as compared to virgin rats. To test the possible positive correlation between serum levels of PRL and the intensity of oxidative burst by peritoneal macrophage, an extra experiment was done with adult virgin female rats treated with domperidone, an antagonist of DA receptors. Domperidone-treated animals showed increased serum levels of PRL and simultaneous increase in peritoneal macrophage oxidative burst. Thus, suggesting an indirect participation of hyperprolactinemia, induced by this treatment in peritoneal macrophage activity of female rats. These results suggest that a previous RE can modulate the activity of dopaminergic hypothalamic systems, while decreasing PRL serum levels and the oxidative burst of peritoneal macrophage. The neurochemical and hormonal RE-induced changes correlate with the immune alterations.
Article
Because many threats exist in an animal's natural habitat, it is important to understand the impact of environmental challenges on maternal-offspring interactions and outcomes. In the current study, a rodent model incorporating the presence of restricted resources and an environmental threat (e.g. predator-related odors and sounds) was investigated. Specifically, pregnant females were assigned to one of four treatments: standard resources, without threat (SR; n = 7); standard resources plus threat (SR-T; n = 8); restricted resources, without threat (RR; n = 7); and restricted resources plus threat (RR-T; n = 6). Maternal rats were moved into the assigned conditions on postnatal day 2 and remained until pups were weaned. Following a standard pup retrieval task on postnatal days 2 and 6, maternal rats were exposed to a retrieval challenge task on postnatal day 8 in which each rat had to traverse a novel barrier to retrieve pups. For neurobiological measures of stress/resilience responsiveness, fecal samples were collected for detection of corticosterone and DHEA metabolites; additionally, immunohistochemistry was conducted on the maternal brains to indicate the presence of Neuropeptide Y (NPY) and Brain Derived Neurotrophic Factor (BDNF) immunoreactivity in the hippocampus, amygdala and hypothalamus. Pup development measures, including body weight and tail length, were also collected. Results suggest that maternal rats with restricted resources exhibited diminished maternal responsiveness that resulted in altered pup development measures; further, restricted resource rats exhibited endocrine markers of compromised emotional resilience (lower DHEA) and decreased neural markers of neuroplasticity (BDNF) and emotional resilience (NPY). Interestingly, predator threat affected various aspects of maternal-pup interactions but had no effect on neurobiological variables, suggesting that restricted resources had a more negative impact on maternal-related outcomes than the presence of predator threat.
Thesis
Der Morbus Alzheimer gehört zum Feld der neurodegenerativen Erkrankungen und äußert sich durch kognitive, vor allem Hippocampus-abhängige Fähigkeiten betreffende, Defizite. Als Ursache werden unter anderem die Amyloid-b-(Ab)-Plaqueablagerungen und eine Störung der adulten hippocampalen Neurogenese vermutet. Epidemiologischen Studien zufolge sind Frauen von einem höheren Morbus-Alzheimer- Erkrankungsrisiko betroffen als Männer. Hormonelle Schwankungen im Leben der Frau, z.B. während der Schwangerschaft, könnten dafür verantwortlich sein. In der vorliegenden Arbeit sollte durch die Beobachtung der Wechselwirkungen zwischen Trächtigkeit und Aβ-Aggregation bzw. adulter Neurogenese ein möglicher Einfluss der Gravidität auf Morbus Alzheimer detektiert werden. Dazu wurden transgene 5xFAD-Mäuse verwendet, welche fünf Mutationen in den Genen für das Amyloid-Vorläufer-Protein (APP) und Präsenilin-1 (PS1) exprimieren. Um Aussagen über den Einfluss von Gravidität auf die Aβ-Aggregation und die adulte Neurogenese machen zu können, wurden 13 bzw. 14 Wochen alte trächtige 5xFAD-Weibchen an Gestationstag 5 bzw. 10 getötet und untersucht. Zur Analyse des Einflusses mehrmaliger Gravidität auf die Morbus-Alzheimer-Pathologie wurden 10 Monate alte 5xFAD-Weibchen, die vier Mal, einmal oder nie trächtig gewesen waren, mit vier Mal und nie trächtig gewesenen Wildtyp-Weibchen ohne familiäre Morbus-Alzheimer-Mutationen verglichen. Zur Quantifizierung der Ab-Aggregation wurden Ab-Immunfloureszenz-Färbungen sowie Kresyl-Violett-Färbungen der Hirnschnitte angefertigt und ein repräsentativer Western-Blot für die in den Hippocampi abgelagerten Ab-Peptide durchgeführt. Die adulte Neurogenese wurde mittels Immunfloureszenz-Färbungen gegen Zellproliferationsmarker (Ki67) und Neurogenesemarker (Doublecortin, DCX) quantifiziert. Ergänzt wurden die Untersuchungen durch einen repräsentativen Western-Blot für das von Neuroblasten und unreifen Neuronen exprimierte DCX. In den jungen 13 bzw. 14 Wochen alten Tieren konnte eine vermehrte Ab-Plaquebildung und zudem eine tendenziell erhöhte Zellproliferation beobachtet werden. Dies spricht für das Vorhandensein modulierender Einflüsse auf die Morbus-Alzheimer-Pathologie während der ersten Hälfte der Trächtigkeit. In den 10 Monate alten Tieren konnten weder in der Ab- Aggregation noch in der adulten Neurogenese Unterschiede zwischen den Gruppen festgestellt werden. Dies lag vermutlich an der weit fortgeschrittenen Ab-Ablagerung und dem Alter der Tiere. Zusammenfassend weisen die Ergebnisse auf eine durch die Trächtigkeit erhöhte Ab- Aggregation und eine zumindest anfänglich erhöhte adulte Neurogenese hin. Vor allem das Fortschreiten der Krankheit scheint somit negativ beeinflusst zu werden. Im Alter scheinen die reproduktiven Erfahrungen jedoch keine Rolle mehr zu spielen.
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and policy discussions on education’s future and so is a natural component of CERI’s “Schooling for Tomorrow” programme. It springs from the awareness that “one-size-fits-all” approaches to school knowledge and organisation are illadapted both to individuals’ needs and to the knowledge society at large. But “personalisation” can mean many things and raises profound questions about the purposes and possibilities for education. The importance of airing these issues led to an international seminar – “Personalised Learning: the Future of Public Service Reform” – held in London in May 2004 bringing together the UK Department for Education and Skills (DfES), the think-tank Demos, and OECD/CERI. The key conference contributions have been elaborated into the chapters that make up this report.
Article
There is a marked increase in the maternal behavior displayed by a female rat following pregnancy—due primarily to exposure to the gonadal hormones progesterone and estradiol (P and E2, respectively). We examined Golgi-Cox silver-stained, Vibratome-sectioned neurons visualized and traced using computerized microscopy and image analysis. In Part One, we examined the hormonal-neural concomitants in the medial preoptic area (mPOA), an area of the brain that regulates maternal behavior, by comparing cell body size (area in μm2; also referred to as soma and perikaryon) in the mPOA and cortex of five groups (n = 4–6/group) of ovariectomized (OVX-minus), diestrous, sequential P and E2-treated (P+E2), late-pregnant, and lactating rats; for Part Two, we examined a subset of mPOA neurons, which were traced in their entirety, from these same subjects. In Part One, whereas there was no difference between OVX-minus and diestrous females, both had smaller somal areas compared to OVX+P+E2-treated and late-pregnant females. The area of the soma returned to diestrous/OVX-minus levels in the lactating females. We found no change among the five groups in area of cell body in cortical neurons, which generally lack steroid receptors. In Part Two, which included a more detailed morphometric analysis of mPOA neurons, we examined several additional measures of dendritic structure, including number of proximal dendritic branches (the largest proximal dendrite was defined as the one with the largest diameter leaving the soma); cumulative length of the largest proximal dendrite; area of the cell body; number of basal dendrites; cumulative basal dendritic length; number of basal dendritic branches; and branch-point (distance from cell body to first branch of largest proximal dendrite). Again, we found similar effects on cell body size as in Part One, together with effects on number of basal dendritic branches and cumulative basal dendritic length in pregnant and P+E2-treated groups compared to OVX, diestrous, and lactating. An increase in somal area denotes increased cellular activity, and stimulatory effects on additional neuronal variables represents modifications in information processing capacity. Pregnancy and its attendant hormonal exposure, therefore, may stimulate neurons in the mPOA, which then contribute (in an as yet undetermined manner) to the display of maternal behavior. During the postpartum lactational period, when cues from pups primarily maintain maternal attention, the neuronal soma appears to return to a pre-pregnancy, non-hormonally dependent state, whereas other aspects of the dendrite remain altered. Collectively, these data demonstrate a striking plasticity in the brains of females that may be reflected in modifications in behavior.
Article
Although aging is inexorable, aging well is not. From the perspective of research in rats and complementary models, reproductive experience has significant effects; indeed, benefits, which include better-than-average cognitive skills, a slowing of the slope of decline, and a healthier brain and/or nervous system well later into life. Work from our lab and others has suggested that the events of pregnancy and parturition, collectively referred to as reproductive experience-an amalgam of hormone exposure, sensory stimulation, and offspring behavioral experience and interaction-may summate to flatten the degree of decline normally associated with aging. Mimicking the effects of an enriched environment, reproductive experience has been shown to: enhance/protect cognition and decrease anxiety well out to two-plus years; result in fewer hippocampal deposits of the Alzheimer's disease herald, amyloid precursor protein (APP); and, in general, lead to a healthier biology. Based on a suite of recent work in organisms as diverse as nematodes, flies, and mammals, the ubiquitous hormone insulin and its large family of related substances and receptors may play a major role in mediating some of the effects of RE on the parameters of aging studied thus far. We will discuss the current set of data that suggest mechanisms for successful biological and neurobiological aging, and the implications for understanding aging and senescence in their broadest terms.
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A key question concerns the extent to which sexual differentiation of human behavior is influenced by sex hormones present during sensitive periods of development (organizational effects), as occurs in other mammalian species. The most important sensitive period has been considered to be prenatal, but there is increasing attention to puberty as another organizational period, with the possibility of decreasing sensitivity to sex hormones across the pubertal transition. In this paper, we review evidence that sex hormones present during the prenatal and pubertal periods produce permanent changes to behavior. There is good evidence that exposure to high levels of androgens during prenatal development results in masculinization of activity and occupational interests, sexual orientation, and some spatial abilities; prenatal androgens have a smaller effect on gender identity, and there is insufficient information about androgen effects on sex-linked behavior problems. There is little good evidence regarding long-lasting behavioral effects of pubertal hormones, but there is some suggestion that they influence gender identity and perhaps some sex-linked forms of psychopathology, and there are many opportunities to study this issue.
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The present work examines the relationship between reproductive experience (comprising breeding, parturition, and lactation) and the behavioral and hormonal processes of fear and stress in the female laboratory rat. Previous research has indicated that reproductive experience functions to decrease the female's stress response in potentially harmful environments, thereby providing her with numerous survival benefits, including decreased fearfulness, increased aggression, and refined hunting skills. This study was designed to determine how nulliparous (no reproductive experience), primiparous (1 reproductive experience) and multiparous (at least 2 reproductive experiences) rats respond to a Pavlovian paradigm of learned fear, involving the pairing of a neutral stimulus (conditioned stimulus) with an aversive stimulus (unconditioned stimulus). We report evidence that reproductive experience is linked with fear-response and anxiety-like behaviors. Our findings indicate that reproductive experience has an additive effect: primiparous mothers showed a different response to the paradigm of conditioned fear not only compared with those of nulliparous rats as well as multiparous mothers. Assessing the complex interconnections among the behavioral and physiologic measures recorded in this study, multidimensional scaling confirmed a clear separation among the 3 groups of rats in terms of the behavioral and physiologic responses to the experimental paradigm, supporting the conclusion that reproductive experience influences the maternal mind.
Article
The female brain is a dynamic structure, which expresses its plasticity most readily following reproductive experience (RE). In Experiment 1, we generated nulliparous (NP), primiparous (PP), and multiparous (MP) females (none, one, and two litters, respectively). Two weeks following the weaning of the first/second six-pup litters, the age-matched MP and PP and the non-pup-exposed NP animals were subjected to a 60-min restraint stress paradigm (enclosure in a Plexiglas restraint tube). The brains were removed and processed for c-fos immunoreactivity (c-fos-IR) in CA3 region of the hippocampus (HI) and in basolateral amygdala (BLA). MP and PP females had very similar numbers of c-fos-IR neurons in both HI and BLA, whereas both were lower than NPs. In a second experiment, the same groups were generated, together with primigravid (PG; first pregnancy) and multigravid (MG; second pregnancy) females, tested in late pregnancy. The animals were exposed to a 30-min trial in an open field and were killed, and the brains were again examined for c-fos-IR. The parous and gravid animals displayed less reactivity to the stress of the open field (i.e., reductions in behavioral measures of anxiety) and significantly less c-fos expression in both CA3 and BLA. The gravid animals displayed significantly less c-fos expression in CA3 and BLA compared to parous females, although neither group differed as a result of a second RE. The data suggest that reproductive (viz., hormonal) and/or maternal (viz., pup exposure) experience may inure a female and her brain to stress, rendering her less susceptible to the behavioral-or other-disruptions that stress sensitivity can produce. Together, these data suggest that the experiences of motherhood (pregnancy, pup exposure, suckling stimulation, etc.) summate to produce reductions in anxiety and stress responsiveness that start before and last long after pup exposure and care. Such reductions may be adaptive in the face of demands placed upon the parous vs. the NP female.
Article
The role of maternal experience (i.e., pregnancy and pup exposure) on rats' performance in a foraging task was assessed. Primiparous (P) and nulliparous (N) animals were either exposed to pups for 21 days (+) or received no pup exposure (-). Following habituation trials, all animals were tested in spatial and cued versions of the dry land maze (DLM) for three days (three trials per day). In the spatial DLM, the presence of pups decreased latencies in both N and P groups in Trial 5 and P+ rats exhibited shorter latencies to baited food wells than P- animals on Trial 6. In the subsequent probe trial, P+ animals spent significantly more time in proximity to the previously baited well than P- rats. Pups enhanced performance of both P+ and N+ groups in trial 6 of the cued test. Thus, in the spatial task, the individual components of the maternal experience (e.g., pregnancy, parturition, lactation, and pup exposure) converge to produce behavioral modifications in the DLM spatial and probe tasks that enable the female to care for her offspring, in this case, by enhancing foraging behavior. Further, in one trial of each version of the task, pup exposure enhanced performance in N animals suggesting that, in isolation, pup exposure may be a more important influence on ancillary maternal behavior than the pregnancy itself.
Article
The current work examined spatial learning and memory (i.e., latencies to find a baited food well) in age-matched nulliparous, primiparous and multiparous (NULL, PRIM and MULT, zero, one or two pregnancies and lactations, respectively). We tested at 6, 12, 18 and 24 months of age in a dry land version of the Morris water maze (Main task), and at 12, 18 and 24 months in the same task in which the original location of the baited well was changed (Reversal task). We show that PRIM/MULT rats, compared to the age-matched NULL females, learned the spatial tasks significantly better and exhibited attenuated memory decline, up to 24 months of age. Furthermore, at the conclusion of behavioral testing, we investigated levels of these animals' hippocampal (CA1 and dentate gyrus) immunoreactive amyloid precursor protein (APP), a marker of neurodegeneration and age-related cognitive loss. MULTs had significantly reduced APP in both CA1 and DG, relative to PRIMs and NULLs, and PRIMs had a trend (p<0.06) toward a reduction in APP compared to NULLs in DG. Further, level of APP was negatively correlated with performance in the two tasks (viz., more APP, worse maze performance). Reproduction, therefore, with its attendant natural endocrine and postpartum sensory experiences, may facilitate lifelong learning and memory, and may mitigate markers of neural aging, in the rat. Combining natural hormonal exposure with subsequent substantial experience with stimuli from the offspring may preserve the aged parous female brain relative to that of NULL females.
Article
Short-term fluctuations in steroid hormones such as estradiol (E2) and progesterone (P) can affect the concentration of hippocampal dendritic spines in adult, cycling nulliparous female rats. Pregnancy is characterized by a significantly longer duration of substantially elevated E2 and P compared to the estrous cycle. Thus, even greater changes than those reported during estrus may be evident. In two experiments, we examined the extent to which reproductive and hormonal state altered the concentration of apical neuronal dendritic spines of the CA1 region of the hippocampus in the following age-matched groups (N's = 7-10/group) of rats: in Exp. 1., CA1 dendritic spine density was examined in nulliparous diestrus (DES), proestrus (PRO), and estrus (ES) females, and late-pregnant (LP) (day 21) and lactating (day 5-6; LACT) females. In Exp. 2, the effects on spine density of a regimen mimicking pregnancy (and that stimulates maternal behavior) were examined, using ovariectomized, no hormone-exposed (OVX-minus) vs. sequential P&E(2)-treated (OVX + P&E2) groups. For both experiments, brains were removed, Golgi-Cox-stained and the most lateral tertiary branches of the apical dendrite of completely-stained hippocampal CA1 pyramidal neurons were traced with oil-immersion at x 1600 and dendritic spine density (# spines/10 micro dendritic segment) recorded. In Exp. 1, spine density was increased in LP and LACT females (which were not different) compared to the other virgin groups, including PRO females, who had more spines than DES and ES. In Exp. 2, OVX + P&E2 displayed significantly more dendritic spines per 10 micro than OVX-minus females (and had numbers that were similar to those of LP and LACT from Exp. 1). Pregnancy and its attendant hormonal fluctuations, therefore, may alter hippocampal neurons that regulate some non-pup-directed components of maternal behavior (e.g., nest building) or behaviors that support maternal behavior (e.g., foraging, associative memory).
Article
Benzodiazepines are frequently prescribed to women for both their anxiolytic and hypnotic effects. Previous studies in rodents have demonstrated reproductive experience, i.e. pregnancy and lactation, can alter sensitivity to certain drugs, such as morphine. The purpose of the present study was to determine whether reproductive experience alters sensitivity to the benzodiazepine, diazepam. Two groups of subjects were generated, a primparous group (pregnancy+21 days of lactation) and an age-matched, nulliparous group. All subjects were injected with diazepam (0.0, 0.5, 2.0 or 2.5 mg/kg) at least 6 weeks after primiparous females weaned their litters. Twenty minutes post-injection, subjects were place in an activity chamber and locomotor behavior was measured. Thirty minutes post-injection, subjects were tested on an automated elevated plus maze. In addition to behavioral testing, diazepam's effects on corticosterone levels were measured. Overall, diazepam's sedative effects on locomotor activity were significantly reduced in primiparous females when compared to nulliparous controls as determined both in the activity chamber and on the elevated plus maze. There was, however, no significant effect of reproductive experience on the anxiolytic effects of diazepam in the elevated plus maze. Finally, while diazepam increased corticosterone in both groups, primiparous females were less sensitive to the effects of the drug on corticosterone secretion. These results indicate that the effects of diazepam on locomotor activity and corticosterone secretion are attenuated following reproductive experience.
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