iliz

n U

Reviewand discuss the potential functional consequences of thesechanges.

Identifying how the brain changes in response to par-enthood could be important to better understand mooddisturbances, including depression, which are known to beprevalent in new mothers and, as suggested by recentstudies, in fathers as well (Box 2). Postpartum mentalillness is often associated with inadequate child care,which has been linked to impaired cognitive and emotionalfunction in offspring [35], including increased likelihood

al changes that accompany the postpartum period alsooccur in fathers that display parenting behavior (Box 1).

Maternal and paternal experiences also influence brainregions that are known to be either unnecessary for thebehaviors directly associated with parenting or only in-volved in a modulatory way. Among these are effectson brain regions associated with cognition and mood,including the hippocampus and PFC (Figure 1).

Parenting and the hippocampusLesions of the hippocampus haveminimal effects on mater-nal behavior [12,13], but this brain region is nonethelessCorresponding author: Gould, E. (goulde@princeton.edu).Parenting and plastBenedetta Leuner, Erica R. Glasper and E

Department of Psychology and Neuroscience Institute, Princeto

As any new parent knows, having a baby providesopportunities for enrichment, learning and stress experiences known to change the adult brain. Yet sur-prisingly little is known about the effects of maternalexperience, and even less about the effects of paternalexperience, on neural circuitry not directly involved inparenting. Here we discuss how caregiving and theaccompanying experiential and hormonal changes influ-ence the hippocampus and prefrontal cortex, brainregions involved in cognition and mood regulation. Abetter understanding of how parenting impacts thebrain is likely to help in devising strategies for treatingparental depression, a condition that can have seriouscognitive and mental health consequences for children.

IntroductionFor all mammalian species, becoming a mother involvesremarkable behavioral change driven by a combination ofneuroendocrine and experiential factors. Considerable re-search has been devoted to understanding the neuralmechanisms of maternal care in rodents and primates.For a small minority of mammalian species (6%), includ-ing humans, fathers play a significant role in rearing young[1,2]. Less is known about the neural and hormonalmechanisms of paternal care but the limited availableevidence suggests that mothers and fathers might recruitsimilar neural circuitry, hormones and neuromodulators inthe service of parenting behavior (Box 1).

There is an increasing body of literature showing thatstructural, electrophysiological and molecular changes oc-cur in the maternal and paternal brain. These includemodifications not only in brain areas known to be involvedin the control of parental behavior, but also in regions nottraditionally associated with parenting, but that are in-stead more widely known to be involved in cognition andmood regulation. Here we highlight maternal and paternalinfluences on neuroplasticity in two such brain regions, thehippocampus and prefrontal cortex (PFC). We also consid-er the complex role that hormones and environment play inmediating the impact of parenting on these brain regions0166-2236/$ see front matter 2010 Published by Elsevier Ltd. doi:10.1016/j.tins.2010.07.003cityabeth Gould

niversity, Princeton NJ 08544, USA

of developing anxiety and depression later in life [6].Elucidating the influence of parenting on the braincould also be critical for ensuring the long-term healthof offspring.

Behavioral changes that define parentingThe postpartum period is a time of dramatic behavioralchanges for allmammalian species. In rodents, females thatwere previously unresponsive or aggressive toward pupsengage in an elaborate repertoire of caregiving activities atbirth and postpartum that includes cleaning the pups,eating the debris of birth, nursing, nest building, lickingandgrooming,pup retrieval, assuminganursing (i.e. archedback) posture over the pups and increased aggression to-ward intruders. In nonhuman primates, maternal behaviorincludes nursing, infant carrying, grooming and defendingthe infant from danger. The emergence of maternal beha-viors is stimulated by contact with offspring and a complexarrayof endocrine changes (Box1).Maternal experienceandthe accompanying hormonal alterations affect various mea-sures of neural plasticity in numerous brain regions such asthe hypothalamus [7,8], amygdala [9] and olfactory bulb[10], areas that are necessary for the full expression ofmaternal behaviors [11].

For most mammalian species, raising the young isaccomplished exclusively by the mother, but for a smallminority fathers play a role. Among species in whichpaternal care occurs (Box 3), there are two general socialstrategies a biparental strategy in which the motherfather dyad care for the young and a cooperative breedingstrategy in which caregiving is shared by the mother,father, older siblings and sometimes unrelated adults.Regardless of whether the species engages in biparentalor cooperative breeding, paternal care typically involvesthe same behaviors as maternal care, with the exception ofnursing. Evidence to date suggests that the neural circuit-ry underlying paternal behavior is similar to that formaternal behavior (Box 1) in that the same brain regionsseem to be activated when fathers and mothers havecontact with infants. Moreover, many of the same hormon-Trends in Neurosciences, October 2010, Vol. 33, No. 10 465

affected by parenting. The hippocampus plays an important structural plasticity are modulated by hormones, including

Box 1. Mothers and fathers are they really so different?

Although significantly less is known about the neural mechanisms ofparenting behavior in fathers than in mothers, evidence suggestsstriking similarities between the sexes. Such similarities are particularlysurprising because maternal behavior has been linked, in part, tohormonal changes that occur with pregnancy, parturition and lactation,experiences that are not available to fathers. From studies of biparentalrodents and primate species that engage in cooperative breeding, weknow that caregiving behavior in fathers is similar to that in mothers,suggesting that the same neural pathways might be involved.Lesion studies, as well as immediate early gene and neuropeptide

distribution studies, in rodents have identified similar brain regionsinvolved in maternal and paternal behavior, including the olfactorybulb, medial preoptic area, lateral septum, bed nucleus of the striaterminalis, amygdala and PFC [8488]. Although less is known aboutthe neural circuitry of parenting in humans, exposure to crying infantsactivates the amygdala and PFC in fathers and mothers, but not innon-parents [62,63]. Given the hedonic aspects of parenting, it is notsurprising that maternal and paternal behavior in rodents involvesreward circuitry, namely dopaminergic afferents [89], suggestingneurochemical and neuroanatomical overlap between the sexes.Similar involvement of reward-related brain regions has beenobserved using neuroimaging in human mothers exposed to photo-graphs of their own happy infants [90], although no study has yetinvestigated this issue in fathers.What role do hormones, with their obvious differences between

mothers and fathers, play? Here the answer is complex. Mothers

exhibit drastic alterations in hormones including decreased estrogenand increased oxytocin and prolactin [11]. These changes are drivenby pregnancy, parturition and lactation, as well as by infant contact,and are important for maternal behavior. Glucocorticoid levels alsoincrease and although important for lactation, are not essential forother aspects of maternal behavior [25,91]. Similar but not identicalalterations in these hormones are detectable in fathers; these includeincreased estrogen, oxytocin, prolactin and glucocorticoids [11,33].Hormonal changes in fathers are induced by contact with the motherand the offspring. For instance, oxytocin levels in human fathers arepositively related to the amount of affection the father displaystoward his infant [92]. Variations in testosterone levels have also beenassociated with paternal care, although studies suggest speciesdifferences. In primate species, including humans, paternal behavioris related to reduced levels of testosterone [33,93]. The opposite is thecase in some rodents for which paternal care is associated withelevated levels of testosterone [9496]. Reduced testosterone, alongwith elevated estrogen and oxytocin levels, might facilitate affiliativebehavior in primate fathers, whereas increased testosterone levels inrodents seem to support parental aggression toward nest intruders. Itremains unclear whether differential hormone responses cause, orare caused by, variation in paternal care, because a definitive linkbetween specific hormones and paternal behavior remains uncertain[97]. Nonetheless, infant contact itself seems to modulate endocrinesystems and activate neural circuitry in fathers in a manner that isstrikingly similar to that in mothers.

Review Trends in Neurosciences Vol.33 No.10role in certain types of learning and memory, anxiety regu-lation and feedback of the stress response. In adult mam-mals, the hippocampus also exhibits a capacity for dramaticstructural reorganization in the form of adult neurogenesis,dendritic remodeling, and the formation and elimination ofdendritic spines and synapses (Figure 1). In virgin animalswithout reproductive ormaternal experience, these formsofBox 2. Depression in new parents

In the US, an estimated 1015% of new mothers experiencepostpartum depression [98]; a slightly lower percentage of men (612%) also experience depression shortly after the birth of a child[99,100]. Among men whose partners have postpartum depression,the rate is even higher, suggesting a link between maternal andpaternal depression [101].Early parental depression is a significant problem, not just for the

afflicted, but also for those in their care. Depression in mothers hasbeen related to persistent disturbances in cognitive and emotionalfunction in offspring [35], including increased likelihood of developinganxiety and depression later in life [6]. Depression in fathers can alsonegatively affect infant development; it has been associated withgreater risk of later emotional, behavioral and cognitive difficulties[100,102,103].Depressed parents seem to provide inadequate care to their

offspring, which in turn impairs emotional and cognitive develop-ment [104]. Parents with depression are less emotionally attached totheir infants, display less affection and interact less overall [3,105],qualities that infants seem to be able to detect. For example, babiesbecome noticeably distressed when an adult (mother, father orunrelated caregiver) maintains a non-interactive still face [106,107].Lack of social interaction during early life probably contributes heavilyto emotional problems that emerge later in the children of depressedparents. Moreover, depressed parents read less often to their childrenthan non-depressed parents, a difference that leads to smallervocabularies in youngsters [100,103].The neural mechanisms by which inadequate parental care

contributes to negative emotional and cognitive outcomes in off-spring are incompletely understood, but animal studies have

466estrogen and glucocorticoids [1419], levels of which arealtered in mothers and fathers (Box 1). Moreover, severalexperiences that seem intrinsic to parenting, such as stress,learning and environmental enrichment, also influence hip-pocampal structure in virgins [1921]. Perhaps it is notsurprising that parental experience alters structural plas-ticity in the hippocampus, although the manner in whichprovided some suggestions. Early postnatal maternal separation isa widely used paradigm to study maternal influence over offspringdevelopment in rats. In adulthood, rat pups subjected to maternalseparation exhibit increased anxiety-like behavior, impaired cognitivecapabilities and dysregulation of the hypothalamuspituitaryadrenalaxis [108]. These effects stem not from maternal separation itself, butindirectly from abnormal parenting behavior exhibited by mothers onreturn to their pups [108]. Similar outcomes have been reported in theoffspring of mother rats that naturally display low levels of maternalcare [109].Maternal separation is associated with diminished structural

plasticity in brain regions linked to cognition and mood regulation,including the hippocampus and PFC. In the hippocampus, maternalseparation and low levels of maternal care lead to suppressedpostnatal neurogenesis [110,111], reduced dendritic spine density[109,112], and reduced hippocampal BDNF expression and choliner-gic innervation [109]. In the PFC, maternal separation, as well aspaternal separation (in biparental species), is associated with changesin dendritic spines and synapses [113115]. If structural changescontribute to behavioral problems associated with inadequateparenting, then the potential to repair these abnormalities bymodulating ongoing plastic processes, including adult neurogenesisand dendritic remodeling, might exist. Indeed, studies have shownthat environmental enrichment, an experience that enhances struc-tural plasticity in adulthood [28,29,47], restores many of thebehavioral abnormalities arising from maternal separation and lowmaternal care during early life [116,117]. Future studies will benecessary, however, to forge the translational link between animalmodels of early inadequate parenting and depressed human parents.

Box 3. Some mammalian species that engage in paternal

care

[(Figure_1)TD$FIG]

Figure 1. Parental experience produces changes in structural plasticity in the

hippocampus and PFC. Top: Schematic diagram of the hippocampus showing the

dentate gyrus, the location of adult neurogenesis (boxed area indicates region

from which photomicrographs were obtained). Mother rats exhibit suppressed

adult neurogenesis in the dentate gyrus prior to weaning of their offspring. (a)

Virgin female rats have more proliferating cells, labeled here with the thymidine

analog bromodeoxyuridine (BrdU) (arrows), compared with postpartum rats (b).

BrdU-labeled cells are stained brown and cells labeled for Nissl are stained purple.

Scale bar, 20 mm. Bottom: Schematic diagram of cortical layers (IVI) in the PFC

showing the neuron type affected by parenting (boxed area indicates layers II/III,

where changes were detected in pyramidal neurons). Father marmosets exhibit

enhanced dendritic spine density on pyramidal neurons of layer II/III PFC

compared to non-fathers. (c) Layer II/III PFC pyramidal cell of a marmoset father

labeled with the lipophilic tracer DiI (fluorescent green). Magnified views of DiI

Review Trends in Neurosciences Vol.33 No.10this occurs seems tobecomplex,mostprobably reflecting themultitude of hormonal and experiential changes associatedwith parenting.

Adult neurogenesisThe dentate gyrus of the hippocampus continues to pro-duce several thousand new neurons each day in youngadulthood [22]. Adult neurogenesis in the hippocampushas been documented in manymammalian species, includ-ing humans [23]. The regulation of adult neurogenesis byhormones and experience has been the subject of intensiveinvestigation [19]. Ovarian steroids enhance [15], whereasadrenal steroids suppress [14,18], cell proliferation in thedentate gyrus of virgin rats. Postpartum female rats ex-hibit decreased estrogen levels [24] and increased gluco-

Rodents Primates

[TD$INLINE] [TD$INLINE]

California mouse Marmoset

Djungarian hamster Owl monkey

Dwarf hamster Siamang

Mongolian gerbil Tamarin

Prairie vole Humancorticoid levels [24,25], suggesting that new neuronproduction might be impaired in mothers. The postpartumperiod is associated not just with hormonal changes, butalso with experiential changes that might impact adultneurogenesis. Stress is known to inhibit, whereas learningand environmental enrichment are known to enhance,adult neurogenesis [1921]. Despite the fact that some ofthe stimuli inherent to parenting seem to enhance adultneurogenesis, available evidence suggests that maternalexperience is associated with suppression of cell prolifera-tion during the postpartum period [2426].

In mother rats, decreased cell proliferation is evident asearly as 1 day after parturition and occurs in both first-time mothers (primiparous) (Figure 1) and females thathave produced more than one litter (multiparous) [2426].By the time of weaning and beyond, cell proliferation isrestored in postpartum females [25]. Thus, maternal expe-rience has a suppressive, albeit temporary, effect on cellproduction in the hippocampus that does not seem to be

labeled dendritic segments showing dendritic spines (arrows) in a control (right

upper) and a father (right lower). Scale bar, 30 mm for cell, 5 mm for dendritic

segments. Adapted, with permission, from Ref. [25,73].

467

modulated by repeated reproductive experience. The sup-pressive effect of maternal experience on adult neurogen-esis seems to be linked to both hormonal changes andinteraction with offspring. Reduced cell proliferation dur-ing the postpartum period is dependent on elevated basalglucocorticoid levels associated with lactation; removal ofnursing pups reduces corticosterone levels and preventsthe decrease in number of proliferating cells [25]. More-over, prevention of increased basal corticosterone levels inpostpartum mothers by means of adrenalectomy and low-dose corticosterone replacement eliminates the reductionin cell proliferation. Thus, it seems that in postpartumfemales, offspring interactions inhibit hippocampal cellproduction through changes in adrenal steroids (Figure2). It should be noted that elevated adrenal steroid levelsmight not be the sole factor involved and that decreasedestradiol levels, which are known to reduce adult neuro-genesis, might participate as well [24,27].

Postpartum-induced suppression of adult neurogenesisis linked to glucocorticoid elevations that occur along withlactation, so it seems likely that this effect might be specificto lactating mothers. The glucocorticoid-induced decrease

in cell proliferation in lactating females suggests thatother aspects of maternal experience, such as enrichingeffects, which would be expected to enhance adult neuro-genesis, are secondary to glucocorticoid changes. Indeed,pup exposure in virgin female rats stimulates adult neu-rogenesis, an effect that might reflect environmental en-richment in the absence of hormonal changes associatedwith pregnancy, parturition and lactation [26]. Studieshave shown that environmental enrichment stimulatesnew neuron production in the dentate gyrus of virgin maleand female rodents [28,29]. Males do not lactate, so itseems reasonable to predict that fathers would displayadult neurogenesis changes that are more akin to enrichedenvironment effects, such as those observed in virginfemales. Consistent with this, brief exposure to pupsincreases cell proliferation in the dentate gyrus of virginmale prairie voles [30]. A similar stimulatory effect of pupexposure on adult neurogenesis has been observed inlaboratory mouse fathers, which do not normally engagein parental behavior, but do so after repeated interactionwith their offspring [31]. By contrast, in Californiamice fathers that naturally demonstrate paternal care

[(Figure_2)TD$FIG]

thro

the d

he C

s of

Review Trends in Neurosciences Vol.33 No.10Figure 2. Parenting can alter anxiety and cognition by inducing structural changes

structural changes that occur with parenting, including suppressed neurogenesis in

the hippocampus, and enhanced dendritic spine density in pyramidal cells of t

glucocorticoid levels might underlie changes in the dentate gyrus and CA3 regionchanges in the CA1 region and PFC. Changes in the structure of the hippocampus and P

with these brain regions, including reduced anxiety-like behavior and enhanced cognit

468ugh potentially different mechanisms. This model diagram illustrates some of the

entate gyrus, reduced dendritic complexity in the CA3 pyramidal cell population of

A1 hippocampal region and layer 23 of the PFC. Parenting-induced elevated

the hippocampus, whereas the enriching aspects of infant contact might produceFC might be responsible for parenting-induced alterations in behaviors associated

ion. Photo credit: J. Alberts (University of Indiana).

behaviors, a reduction in new cell production, similar tothat detected in mother rats, has been observed [32]. Thiseffect is probably linked to hormonal changes that occur infathers. For example, fathers exhibit elevated glucocorti-coids [33], although this hormonal change is not associatedwith lactation.

Many of the behavioral and neuroendocrine adaptationsof the postpartum period are also evident during latepregnancy [34]. Thus, it seems plausible that suppressionof the production of new neurons would emerge beforeparturition. Decreased hippocampal volume has been ob-served in pregnant rats and humans [35,36], suggestingthat reduced adult neurogenesis contributes to these volu-metric changes. Cell proliferation in the hippocampus doesnot seem to be altered during pregnancy in rats or mice[10,3739] and the current evidence on pregnancy-inducedalterations in cell survival is mixed, with some worksuggesting a possible enhancement [37] and other studiesshowing a decrease [40] or no effect [39]. It is possible thatthese inconsistencies are related to the different gestation-al timepoints examined and could suggest that neurogen-esis is altered, but only at specific times during pregnancy.

Despite the unresolved effects of pregnancy, some evi-dence suggests that maternal experience has a lastingeffect on progenitor cells in the dentate gyrus that extendsinto aging. Whereasmiddle-aged virgin female rats exhibitno change in cell proliferation with estrogen treatment,middle-aged mothers exhibit an increase in cell prolifera-tion, an effect similar to that observed in young adults [41].This suggests that maternal experience slows the agingprocess, at least insofar as estrogen sensitivity of progeni-tor cells is concerned. The duration of this effect remainsunknown. Long-term benefits of being a mother on age-related cognitive decline and othermeasures of brain aginghave also been reported [42].

It is important to note thatmaternal experience also haseffects on neurogenesis in the subventricular zone (SVZ),an area that gives rise to neurons of the olfactory bulb, abrain region important for maternal care [43]. Increasedneurogenesis has been reported in mice and rats duringpregnancy and the early postpartum period [10,38]. Pupexposure in virgin female rats also stimulates neurogen-esis in the SVZ [44]. In contrast to the involvement ofglucocorticoids in the postpartum reduction in neurogen-esis in the hippocampus, increased neurogenesis in theSVZ seems to be mediated by prolactin [10]. Thus, mater-nal experience can have opposite effects on the same formof structural plasticity in two different brain regionsthrough distinct mechanisms.

Dendritic and synaptic remodelingThe effects of parenting on hippocampal plasticity are notlimited to alterations in cell proliferation and neurogen-esis, but also extend to dendritic spines and architecture.Like the effects of maternal experience on adult neurogen-esis, changes in thesemorphological measures are complex(Figure 2).

Increased spine densities on apical dendrites of hippo-campal CA1 pyramidal neurons have been reported in late

Reviewpregnant and postpartum (primiparous) rats [45,118]. Thepostpartum period is also associated with increases inspine density on dendrites of dentate gyrus granule cells[118]. Hippocampal dendritic spine density is controlled bycirculating levels of ovarian hormones [17], so enhancedspine density in late pregnancy might be related to elevat-ed estrogen levels that occur at this time. In support of this,virgin females treated with a pregnancy-like regimen ofestradiol and progesterone exhibit similar spine enhance-ments [45]. Estrogen levels are low after birth, so it is likelythat estrogen does not mediate the enhanced spine densitypostpartum. It is possible that the spines generated duringlate pregnancy are maintained postpartum or that thelatter diminish and new spines are generated [46]. Thespecific hormonal or environmental stimuli that maintainor induce spine growth postpartum have yet to be deter-mined. One possibility is that postpartum increases inspine density result from the enriching effects of maternalexperience (Figure 2). In addition to its positive effect onthe production of new neurons, environmental enrichmentis known to have a beneficial effect on dendritic spines inthe hippocampus [19,47].

To date, no time-course studies have examined theduration of dendritic spine changes throughout the post-partum period. It does not seem that spine density remainselevated in primiparous females at the time of weaning,indicating that enhanced dendritic spine density might betransient and dependent on the presence of offspring [48].Another possibility is that the persistence of dendriticspines may be modulated by reproductive experience. Con-sistent with this are data showing that unlike primiparousfemales, multiparous females at weaning have more hip-pocampal dendritic spines compared to virgins, althoughthis effect is specific to CA1 basal dendrites [48,49].

Dendritic architecture in the hippocampus is also influ-enced by maternal experience. Primiparous rats exhibitdecreased dendritic length and fewer dendritic branchpoints on pyramidal neurons in both the CA1 and CA3regions of the hippocampus relative to virgin and multipa-rous females [48]. It is important to note that these resultswere observed in postpartum females after weaning, leav-ing open the possibility that alterations in dendritic archi-tecture emerge earlier in the postpartum periodwhen pupsare present. The factors responsible for dendritic treeshrinkage have yet to be determined. High levels of circu-lating glucocorticoids have been associated with dendriticatrophy of pyramidal cells in the hippocampus [16,50], butdid not correlate with hippocampal dendritic remodelingaround the postpartum period [48]. A role for glucocorti-coids cannot be ruled out because levels were measured atthe time of weaning and not during pregnancy or postpar-tum, when hormonal changes are likely to be more evidentand contribute to dendritic remodeling.

Synaptic plasticity and gene expressionIn addition to structural changes, alterations in hippocam-pal synaptic plasticity also occur in the postpartum period.Compared to virgin females, long-term potentiation (LTP)is enhanced in hippocampal slices from multiparous miceduring the early postpartum period of their second litter[51]. Oxytocin might be an important mediator of this

Trends in Neurosciences Vol.33 No.10effect, because LTP was also enhanced in hippocampalslices of virgins treated with this neuropeptide [51].

469

Similarly, anenhancement inLTP is evident inprimiparousfemales after weaning [52]. These effects are surprisingbecause other hormonal changes associated with the post-partum period, such as reduced estrogen and increasedglucocorticoid levels, have been linked to impaired LTP[53,54]. Taken together, the results suggest that factorsin the maternal brain might buffer against some of thenegative influences associated with hormonal changes.

Maternal experience is also associated with changes inthe expression of genes, such as those encoding GABAAreceptor subunits and neuropeptides, in the hippocampusand other brain regions that are likely to influence synapticplasticity [5557]. Whether parenting-induced changeshave a positive, neutral or negative effect on behaviorremains largely undetermined, although a recent studyhas demonstrated abnormal postpartum behaviors in micewith deficiencies in d-subunit-containing GABAA receptors[58].

Parenting and the prefrontal cortexThe PFC is activated by parenting behavior in both rodentsand humans [5963]. Lesions of the PFC do not have aprofound effect on the initiation of parenting behavior,although some evidence in rodents suggest that pup re-trieval can be affected [64]. The PFChas been implicated inmany functions that might indirectly influence parenting,including working memory, cognitive flexibility and moodregulation [65,66].

Structural reorganization has been observed in the PFCof rodents and primates. As in the hippocampus, thesechanges can be induced by alterations in hormones andexperience. Manipulation of estrogen and glucocorticoidsaffects dendritic architecture and dendritic spine densityon pyramidal neurons of the medial PFC [6770]. More-over, experiences that seem to be related to parenting, suchas stress and enriched environment living, also alter den-dritic complexity and spine density in this brain region[47,71,72].

Structural reorganization occurs in the PFC of marmo-set fathers. Marmoset fathers engage in extensive caregiv-ing behavior by carrying, protecting and feeding the young(Box 3) [73]. Marmoset fathers, regardless of whether theyare first-time or experienced, have enhanced dendriticspine density on pyramidal neurons of the PFC [73]. Apossible involvement of vasopressin, a neuropeptide impli-cated in paternal care [33], was also suggested by thedemonstration that parallel increases in the abundanceof vasopressin V1a receptors, and the proportion of den-dritic spines that were labeled for this receptor, occurred inthe PFC of fathers. The abundance of V1a receptors corre-lated negatively with offspring age, so these effects mightnot be permanent, but instead might be driven by fatheroffspring interactions, which lessen as offspring mature.As with some of the effects of maternal experience onhippocampal structure, hormones and offspring probablywork together in some way to alter the PFC of fathers. Inthis regard, it is worth noting that living in an enrichedenvironment, in the absence of caregiving experience, issufficient to induce similar changes in dendritic spine

Reviewdensity of pyramidal neurons in the PFC of marmosets[47]. These findings suggest that the enriching aspect of

470parenting might be important for driving changes in thebrains of marmoset fathers (Figure 2).

Female rats also exhibit increased dendritic spine den-sity on pyramidal neurons of the medial PFC during thepostpartum period [118]. In addition, glial changes havebeen reported in specific PFC regions of postpartum rats[74]. The extent to which these structural changes directlyinfluence cognitive function remains unknown, but recentevidence indicates that mother rats perform better thanvirgins on attentional set shifting, a cognitive behavioraltask that requires the PFC [118].

Functional consequences of parenting-inducedneuroplasticityThe fact that maternal and paternal experience can re-model neural systems not directly related to parental caresuggests that functions mediated by these brain regionsmight also be altered. Numerous studies in non-parentshave linked adult neurogenesis and dendritic remodelingto hippocampal functions, including learning and memory,anxiety regulation and stress responses [19,21,75,76]. Anincreasing body of evidence suggests that maternal expe-rience alters behaviors associated with the hippocampus,including enhanced spatial navigation learning and re-duced anxiety-like behaviors [24,52,7782]. The extent towhich maternal experience-induced changes in hippocam-pal structure contribute to changes in hippocampal func-tion, however, remains unexplored. Likewise, the influenceof paternal experience on hippocampal function has beenalmost completely ignored, but given the similarities ob-served between mothers and fathers, it seems likely thatchanges in hippocampal function occur. Recent evidencesuggests that changes in adult neurogenesis in fathersmight be linked to kin recognition, at least in some species[31]. It is also likely that functionsmediated by the PFC arealtered by parenting, because structural plasticity in thisbrain region has been linked to alterations in PFC-depen-dent cognitive behavior [72,118]. Finally, given the con-nections between the hippocampus and the PFC, as well asthe involvement of this pathway in the regulation of anxi-ety-like behavior [83], it is possible that the combinedaction of parenting on structural plasticity in both thehippocampus and the PFC could mediate modulation ofmood in mothers and fathers.

ConclusionAlthough it has long been recognized that parental carecan have a profound influence on offspring wellbeing, onlyrecently has there been an appreciation of the impact ofoffspring on parents. The brains of parents are clearlydifferent from those of non-parents, having been changedby the presence of offspring and corresponding hormonalfluctuations. Available evidence suggests that structuralreorganization occurs in the hippocampus and PFC ofmothers and fathers, but these studies are incompleteand the link between changes in brain structure andfunction remains unexplored (Box 4). Future studies fo-cused on identifying brain changes, as well as the relatedbehaviors, that are influenced in both mothers and fathers

Trends in Neurosciences Vol.33 No.10will fill the gaps in our knowledge of how the brain isinfluenced by childrearing.

Review Trends in Neurosciences Vol.33 No.10AcknowledgmentsThis work was supported by grants from the National Institute of MentalHealth (MH54970 to E.G. and MH084148 to B.L), a NARSAD YoungInvestigator Award (B.L.) and a Ruth L. Kirschstein postdoctoral NRSAfellowship from the National Institute on Aging (E.R.G.).

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Box 4. Unanswered questions

What are the hormonal and neural mechanisms that underliereduced anxiety and improved cognition in parenting?

How do changes in structural plasticity influence brain function inparents?

Are there fundamental differences in the brains of mothers andfathers and, if so, to what extent are these differences driven byexperience and hormones?

Do experienced parents undergo additional modifications in brainstructure or are parenting-related brain changes specific to first-time parents?

How does the parenting brain cope with high levels of glucocorti-coids?

Are parenting changes induced primarily by newborn cues or doolder offspring elicit similar changes?

Do changes in brain structure contribute to mood disorders inparents?revealed by the Golgi method. Neuroscience 126, 83984710 Shingo, T. et al. (2003) Pregnancy-stimulated neurogenesis in the

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Review Trends in Neurosciences Vol.33 No.10473

Parenting and plasticityIntroductionBehavioral changes that define parentingParenting and the hippocampusAdult neurogenesisDendritic and synaptic remodelingSynaptic plasticity and gene expression

Parenting and the prefrontal cortexFunctional consequences of parenting-induced neuroplasticityConclusionAcknowledgmentsReferences