strogen Receptor-Distribution in Male Rodents Is Associated with Social …

Estrogen Receptor-?Distribution in Male Rodents Is Associated with Social

Organization

BRUCE S.CUSHING1*AND KATHERINE E.WYNNE-EDWARDS2 1The Brain-Body Center,Department of Psychiatry,University of Illinois at Chicago,

Chicago,Illinois60612

2Department of Biology,Queen’s University,Kingston,Ontario K7L3N6,Canada

ABSTRACT

It has been hypothesized that site-speci?c reduction of estrogen receptor-?(ER?)is associ-ated with the expression of male prosocial behaviors.Speci?cally,highly social males are pre-dicted to express signi?cantly lower levels of ER?than females and less social males in brain regions associated with prosocial behavior including the bed nucleus of the stria terminalis(BST) and the medial amygdala(MeA).This hypothesis was tested by comparing ER?immunoreac-tivity(IR)in three species of microtines,the polygynous montane(Microtus montanus)and meadow(M.pennsylvanicus)voles and the monogamous pine vole(M.pinetorum),and two species of cricetines that differ in the extent of social pair-bond formation,Siberian(Phodopus sungorus)and Djungarian(P.campbelli)hamsters.As predicted,ER?-IR was sexually dimorphic in the BST and MeA of the highly social species,with females expressing more ER?-IR cells than males.Male and female montane voles did not differ.Male and female meadow voles differed in the ventromedial hypothalamus,with females expressing more ER?-IR cells.Male pine voles expressed lower levels of ER?-IR in the MeA than male montane and meadow voles and in the BST relative to montane males.Male Djungarian hamsters,which show higher levels of parental care,had fewer ER?-IR cells in the BST than male Siberian hamsters.Results indicate that the distribution of ER?differs relative to the continuum of species-typical af?liative behavior and supports the hypothesis that ER?has a signi?cant role in regulating species-speci?c social https://www.wendangku.net/doc/9b10651507.html,p.Neurol.494:595–605,2006.?2005Wiley-Liss,Inc.

Indexing terms:ER?;medial amygdala;bed nucleus of the stria terminalis;social monogamy;

Microtus;Phodopus

In contrast to most male mammals,socially monoga-mous males display high levels of prosocial behavior and low levels of aggression(Kleiman,1977).Prosocial behav-ior consists of“positive”social interactions,such as af?li-ative behavior,including the formation of long-term bonds and parental care.It has been hypothesized that a reduc-tion in expression of ER?in males plays a role in the increased expression of male prosocial behaviors(Cushing et al.,2004).During development,estrogen stimulates the initial masculinization of male neural structures and be-haviors(Kendrick and Drewett,1980;Hutchison,1997; Hans and De Vries,2003).Studies with estrogen receptor-?(ER?)knockout mice indicate that estrogen regulates a number of social behaviors,including explora-tion of novel individuals(Roselli and Chambers,1999; Wersinger and Rissman,2000),partner preference(Bak-ker et al.,2002),aggression(Ogawa et al.,1997),scent marking(Vagell and McGinnis,1998),and copulatory be-havior(Rissman et al.,1999),and that ER?typically masculinizes male behavior(Scordalakes et al.,2002; Scordalakes and Rissman,2004;Kudwa et al.,2005).In polygynous species,male typical social behavior is associ-ated with increased aggression and lower levels of proso-cial behavior.If estrogen masculinizes male behavior, then reducing the expression of ER?in regions of the brain that regulate prosocial behavior may enhance male prosocial behavior(Cushing et al.,2004).

Grant sponsor:National Institutes of Health/National Institute of Child Health and Human Development;Grant number:MH01992;Grant num-ber:HD38490.

*Correspondence to:Bruce S.Cushing,The Brain-Body Center,Depart-ment of Psychiatry,University of Illinois at Chicago,Chicago,IL60612. E-mail:bcushing@https://www.wendangku.net/doc/9b10651507.html,

Received6April2005;Revised1July2005;Accepted29August2005 DOI10.1002/cne.20826

Published online in Wiley InterScience(https://www.wendangku.net/doc/9b10651507.html,).

THE JOURNAL OF COMPARATIVE NEUROLOGY494:595–605(2006)?2005WILEY-LISS,INC.

This hypothesis was initially tested by comparing the expression of ER?between two behaviorally distinct pop-ulations of prairie voles(Microtus ochrogaster;Cushing et al.,2004).Although they are classi?ed as socially monog-amous(Getz et al.,1981),there are signi?cant interpopu-lational differences in the degree of sociality,with prairie voles from Kansas being much less social than Illinois prairie voles and displaying a number of characteristics typically associated with polygyny(for review see Cushing and Kramer,2005).The?ndings indicated two major dif-ferences.First,Illinois prairie voles displayed a greater degree of sexual dimorphism in ER?-IR,females more than males.Second,Illinois males expressed signi?cantly lower levels of ER?-IR in the bed nucleus of the stria terminalis(BST)and medial amygdala(MeA)than Kan-sas males(Cushing et al.,2004).Other studies with prai-rie voles also suggest that ER?distribution is associated with male prosocial behavior.Neonatal castration signif-icantly increased the expression of ER?in the BST and MeA(Cushing and Kramer,2005).In both of these stud-ies,changes in the expression of ER?were observed in the BST and the MeA.These two brain regions regulated the expression of a number of sociosexual behavior,including af?liation and aggression behavior(Wang and De Vries, 1993;De Vries and Villalba,1997;Wang et al.,1997; Newman,1999).Therefore,changes in these regions could directly affect the expression of prosocial behavior,and neonatal castration inhibited the expression of alloparen-tal parental behavior(Lonstein et al.,2002)and inhibited the formation of partner preferences(Cushing et al., 2003).Finally,a comparison of ER?between female meadow and prairie voles indicated that less social meadow vole expressed higher levels of ER?(Fowler et al., 2005).

Therefore,the purpose of this study was to determine whether the relationship between ER?and degree of so-ciality,especially in males,could be extended to other species and whether the same regions of the brain were involved.This was accomplished by comparing the expres-sion of ER?within two distinct groups of rodents.First, ER?was compared in three microtine species:two polyg-ynous species,montane(M.montanus;Jannet,1980)and meadow(M.pennsylvanicus;Madison,1980)voles,and the monogamous pine vole(M.pinetorum;Dewsbury, 1981).Although the behavior of male meadow voles is usually typical of polygynous males(an absence of pair bonds,high levels of aggression,and no parental care), there are conditions under which male meadow voles dis-play signi?cant prosocial behavior,including parental care(Storey et al.,1994;Parker and Lee,2001).Based on the varying degrees of prosocial behaviors typical of these species-speci?c predictions about the expression of ER?were:1)montane voles would display the least female-biased sexual dimorphism and pine voles the most;2)pine voles would express this sexual dimorphism in the BST and MeA;3)montane males would have signi?cantly higher numbers of ER?-immunoreactive(-IR)cells in the BST and MeA than pine voles;and4)ER?-IR in meadow voles would be intermediate,but,based on their classi?-cation as polygynous,ER?-IR would be more similar to that in montane than in pine voles.

The second test of the hypothesis was conducted by using two species of dwarf hamsters,Siberian(Phodopus sungorus)and Djungarian(P.campbelli)hamsters.Male Djungarian hamsters provide extensive paternal care that includes midwife behavior,whereas Siberian hamster males have only seasonal opportunities to interact with pups and provide little direct paternal care(Wynne-Edwards,1995,1998;Jones and Wynne-Edwards,2000; Schum and Wynne-Edwards,2003).In contrast to the voles,na?¨ve adult males of both species of dwarf hamster have circulating levels of estradiol as high as those of females(Schum and Wynne-Edwards,2003).High male estradiol might in?uence ER?expression and therefore provides a robust second test of the generality of the hypotheses.Thus,we predicted that expression of ER?-IR would be sexually dimorphic in both species in the BST and MeA;females were expected to express signi?cantly more ER?than males.Furthermore,we predicted that male Siberian hamsters would express higher levels of ER?than Djungarian males in these regions.

MATERIALS AND METHODS

We conducted two experiments to determine whether the relationship between ER?and the degree of sociality observed between populations of prairie voles could be generalized to other species.In experiment1,ER?-IR was compared in three species of voles,polygynous montane, polygynous/conditionally social meadow,and monoga-mous pine voles.Meadow voles were obtained from a stock that originated in Tennessee,pine voles from a stock that originated in North Carolina,and montane voles from Idaho.Animals were housed in the same colony for at least 2months on a14/10-hour light dark cycle prior to collec-tion of tissue.Brains were collected from sexually na?¨ve adults during the summer.All males were scrotal.Female voles do not experience a spontaneous estrous cycle,in-stead requiring exposure to a novel male to stimulate the onset of estrus.Therefore,all females were in the same reproductive state at the time of collection.However,a vaginal lavage was performed on all females at the time brains were collect to con?rm their reproductive state. Animals were housed in accordance with the USDA and NIH guidelines,and prior to any research all procedures were approved by the University Animal Care and Use Committee.

In experiment2,ER?-IR was compared within and be-tween Siberian and Djungarian hamsters.Dwarf ham-sters were obtained from an established colony at Queens University,Kingston,Ontario,Canada(Wynne-Edwards, 1998,2003).All subjects were sexually na?¨ve adults. Males were scrotal.In females,a vaginal lavage was per-formed prior to collection,and tissue was collected only when diestrus cytology was evident.During perfusion, conditions of oviduct and uterus were examined to con?rm the results of the vaginal lavage.

Localization of ER?-IR

To compare and contrast the distribution of neurons expressing ER?-IR within and between species,brains were collected and the expression of ER?-IR compared in males and females(n?4–7per species and sex).The following is a brief description of tissue?xation and im-munocytochemistry(for complete details see Cushing et al.,2004).Brains were?xed via transcardial perfusion with4%buffered paraformaldehyde and2.5%acrolein. Fixed brains were stored in25%sucrose at4°C until they were sectioned at30?m on a freezing sliding microtome. Sections were stored at–20°C in cryoprotectant(Watson

596 B.S.CUSHING AND K.E.WYNNE-EDWARDS

et al.,1986)until they were processed by ABC immuno-

cytochemistry(ICC)staining for ER?.Prior to incubation

in the primary antibody,tissue was rinsed in0.05M

KPBS and then10%sodium borohydride.Next,sections

were incubated with rabbit ER?polyclonal antibody

C1355,which is directed against the last14amino acids of

the rat ER?(Upstate Biotechnology,Whaltham,MA;anti-

ER?C1355)at a dilution of1:100,000in0.05M KPBS-

0.4%Triton X-100for48hours.The antibody was gener-

ated against the last15C-terminal amino acids of the rat

ER?protein,a region that shares no homology with ER?,

and it binds to both free and bound receptors,reducing

variation in staining resulting from potential differences

in circulating hormone levels(Murphy et al.,1995).The

speci?city of C1355was originally tested/veri?ed by using

preadsorption with the synthetic peptide used to produce

the C1355ER?antibody(Moffatt et al.,1998)and immu-

noblot with rat ER?transfected Cos-1cells(Schreihofer et

al.,1999).We con?rmed speci?city in voles and dwarf

hamsters by performing ICC after preadsorption with the

synthetic peptide(ten times the concentration of antibody)

against which the antibody was raised and also by omit-

ting the primary antibody from the ICC procedure.No

staining was observed in either case.

After incubation in C1355,tissue was rinsed in KPBS

and then incubated for1hour at room temperature in

biotinylated goat anti-rabbit IgG(1:600dilution in0.4%

Triton X-100).Sections were then incubated in an avidin-

biotin peroxidase complex(Vectastain ABC Kit-Elite pk-

6100standard;Vector,Burlingame,CA;4.5?l A and4.5?l B per1ml solution)for1hour.Sections were then rinsed in KPBS,followed by0.175M sodium acetate.

Finally,ER?was visualized by using a nickel sulfate-

diaminobenzine chromogen solution(250mg nickel II sul-

fate2mg DAB,8.3?l3%H

2O

2

in10ml sodium acetate).

Sections were mounted onto subbed glass slides and air dried overnight.To aid in identifying speci?c brain re-gions,slides were counterstained with neutral red prior to dehydration in ascending ethanol solutions,cleared in Histoclear,and coverslipped with Histomount.Image analysis was used to determine the number of cells ex-pressing ER?-IR in the medial preoptic area(MPOA),bed nucleus of the stria terminalis(BST),arcuate nucleus (ARC),ventromedial nucleus of the hypothalamus(VMH), and medial amygdala(MeA).These areas were chosen because they are involved in a variety of aspects of repro-duction and social behavior.

Image analysis

The number of cells expressing ER?-IR was determined in IPLab(Scanalytics,Inc.,Fairfax,VA)image analysis software at?40.Slides were coded and scored and cells counted bilaterally and then averaged,by an experimen-tally blind scorer.Cells with levels of nickel-DAB staining that were greater than background were classi?ed as ex-pressing ER?.Background levels were established by us-ing adjacent areas that do not contain ER?,and IPLab was then adjusted to count only cells with levels above background staining.Photomicrographs(see Figs.2,4) were captured in IPLab and then converted to gray scale, sized/cropped,and labeled in Abode Photoshop7.0.

Statistical analysis

Between-population differences were determined in voles by using a one-way ANOVA for each sex and region.Sexes were analyzed separately because a priori we ex-pected there to be signi?cant differences between males and females and did not want to confound treatment ef-fects with this difference.When the overall ANOVA was signi?cant,a Fisher’s PLSD was used to make post-hoc pairwise comparisons.A t-test was used to test for differ-ences in ER?-IR between sexes within species and to test for differences between hamster species.Statistical tests were conducted separately for each brain region.Results were considered signi?cant at P?0.05.

RESULTS

Experiment1:ER?-IR in voles Expression of ER?-IR was species and site speci?c. Across vole species,males differed in the number of cells expressing ER?-IR in the BST[F(2,17)?9.8,P?0.01] and the MeA[F(2,16)?7.7,P?0.01;Figs.1,2].In the BST,male montane and meadow voles had more cells expressing ER?-IR than male pine voles(Fisher’s PLSD mean diff?447,P?0.001;mean diff?307,P?0.05, respectively),whereas,in the MeA,montane males had more ER?-IR cells than pine voles(Fisher’s PLSD mean diff?247,P?0.005).Among females,there were no signi?cant species differences in any brain region(Figs.1, 2).Within species,the degree of sexual dimorphism in the expression of ER?-IR differed between species(Figs.1,2). There were no signi?cant differences between male and female montane voles.In meadow voles,females ex-pressed signi?cantly more ER?-IR in the VMH than males (t

10?3.5,P?0.001),whereas,in pine voles,females expressed more ER?-IR than males in the BST(t

7?12.1, P?0.0001),VMH(t

7?2.52,P?0.05),and MeA(t7?8.7, P?0.0001).

Experiment2:ER?-IR in dwarf hamsters Male Djungarian hamsters had signi?cantly fewer

ER?-IR cells in the BST(t

10?2.57,P?0.05)and the MeA(t

9?2.72,P?0.05)than females,whereas male Siberian hamsters had fewer ER?-IR cells in the BST

(t

10?2.67,P?0.05),MeA(t10?4.02,P?0.05),ARC (t

10?2.74,P?0.05),and VMH(t10?4.54,P?0.05)than females(Figs.3,4).In regions where there were signi?-

cant intrasexual differences between Djungarian and Si-berian,Djungarian expressed less ER?-IR than Siberian. Male Djungarian expressed lower levels of ER?in the BST (t

10?3.05,P?0.05),whereas female Djungarian had lower levels in the ARC(t

10?3.56,P?0.05)than their Siberian counterparts.

DISCUSSION

The results from this study supported the two main predictions.First,males of highly social rodents display lower site-speci?c levels of ER?-IR than polygynous males,and,second,ER?-IR is sexually dimorphic in highly social species.The socially monogamous male pine voles displayed signi?cantly lower levels of ER?-IR in the BST and MeA than the polygynous montane vole and in the MeA compared with male meadow voles.Additionally ER?-IR was sexually dimorphic in the three social species, pine voles and Djungarian and Siberian hamsters,with males expressing signi?cantly fewer ER?-IR cells in the BST and MeA than females.

597

ER?AND SOCIAL ORGANIZATION

ER ?patterns and the expression of male

prosocial behavior

Until recently,the main focus of study of the regulation of monogamous social behavior has been on the neuropep-tides oxytocin and vasopressin.Neuropeptides play a role in regulating a variety of social behaviors (Insel et al.,1998;Young and Wang,2004);there are signi?cant differ-ences in the distribution of oxytocin and vasopressin re-ceptors between monogamous and polygynous rodent

spe-

Fig.1.a–e:Expression of ER ?in the brains of montane,meadow,and pine voles.Data are presented from the least social species to the most social.There were no signi?cant differences in ER ?-IR between males and females in montane voles,whereas ER ?-IR is sexually dimorphic in the ventromedial nucleus of the hypothalamus (VMH)of meadow voles and the bed nucleus of the stria terminalis (BST)and medial amygdala (MeA)in pine voles.Male pine voles express signif-icantly lower levels than montane and meadow vole males in the BST and male montane voles in the MeA.ARC,arcuate nucelus,MPOA,medial preoptic area.Different letters indicate signi?cant same-sex differences.*Signi?cant within-population difference between males and females.

598 B.S.CUSHING AND K.E.WYNNE-EDWARDS

cies (Insel et al.,1991;Insel and Shapiro,1992);and viral vector enhancement of vasopressin receptors (V1a)can alter behavioral af?liation (Lim et al.,2004).Although there is no doubt that the oxytocinergic and vasopressin-ergic systems play an important role in regulating social behavior,changes in these systems may not be suf?cient to explain the evolution of social monogamy.

First,the effects of both oxytocin and vasopressin are steroid dependent (De Vries et al.,1984,1985;Arletti and Bertolini,1985;Caldwell et al.,1986),with estrogen

hav-

Fig.2.a–l:Representative photomicrographs of ER ?-IR in bed nucleus of the stria terminalis (BST)and medial amygdala (MeA)of male and female montane (female a and g,male d and j),meadow (female b and h,male e and k),and pine voles (female c and i,male f and l).Scale bars ?100?m in d (applies to a–f),j (applies to g–l).

599

ER ?AND SOCIAL ORGANIZATION

ing a direct effect on the expression of oxytocin receptors (Coirini et al.,1989;Johnson,1992)and the V1a vasopres-sin receptor (Funabashi et al.,2000).Estrogen also can directly in?uence the production of oxytocin and vasopres-sin (Plumari et al.,2002),in that there is an estrogen response element in the promoter region of both oxytocin and vasopressin genes (Bale and Dorsa,1997;Shapiro et al.,2000).This suggests the possibility that estrogen could play a role in the establishment of the response to neu-ropeptides.Second,studies using ER ?knockout mice or aromatase inhibitors indicate that estrogen plays a direct role in regulating many of the same social behaviors as-sociated with the oxytocin and vasopressin,including partner preference (Bakker et al.,2002),

aggression

Fig. 3.a–e:Expression of ER ?in the brains of Siberian and Djungarian hamsters.The expression of ER ?-IR was sexually dimor-phic in both hamsters.Females expressed more ER ?-IR than males in the bed nucleus of the stria terminalis (BST)and medial amygdala (MeA),whereas in Siberian hamsters females also expressed more than males in the ventromedial nucleus of the hypothalamus (VMH)and arcuate nucleus (ARC).Male Djungarian hamsters expressed

signi?cantly lower levels of ER ?-IR than male Siberian hamsters in the BST,whereas female Djungarian expressed signi?cantly lower levels in the ARC than female Siberian hamsters.MPOA,medial preoptic area.Horizontal lines indicate signi?cant within-sex differ-ences.*Signi?cant within population difference between males and females.

600 B.S.CUSHING AND K.E.WYNNE-EDWARDS

Fig.4.a–h:Representative photomicrographs of ER?-IR in female and male Siberian(female a and e,male c and g)and Djungarian(female b and f,male d and h)hamsters in the bed nucleus of the stria terminalis(BST;a–d)and the medial amygdala(MeA;e–h).Scale bars?100?m in c(applies to a–d), g(applies to e–h).601

ER?AND SOCIAL ORGANIZATION

(Ogawa et al.,1997),and parental behavior(Ogawa et al., 1998;Trainor and Marler,2002).Third,although there are signi?cant species differences,the expression of OT and the V1a vasopressin receptor is not sexually dimor-phic(Insel and Shapiro,1992;Insel et al.,1994).The similarity in the distribution of receptors fails to explain why it has been repeatedly demonstrated that oxytocin plays a greater role in the regulation of female behavior, whereas vasopressin is more important in males(Winslow et al.,1993;Williams et al.,1994;Insel and Hulihan,1995; Insel et al.,1998;Cushing and Carter,2000;Cushing et al.,2001).The similar pattern,but differential response, suggests that other factors are involved in regulating the overall response to these neuropeptides.Finally,many male-typical behaviors associated with polygyny are reg-ulated by estrogen rather than neuropeptides.Taken to-gether,these facts suggest that altering the response to estrogen could play a critical role in regulating both the decrease in male-typical behaviors and the increased prosocial behavior associated with social monogamy. Reduction in ER?-IR and the expression of

male prosocial behavior

Early studies that manipulated circulating levels of tes-tosterone in males demonstrated that testosterone was suf?cient and necessary for the expression of male“typi-cal”behavior and reproductive physiology.However,more recent studies have demonstrated that many of the effects initially attributed to testosterone do not result from an-drogens,but instead are mediated by estrogen formed by intracellular aromatization of testosterone(Ogawa et al., 1997;Vagell and McGinnis,1998;Rissman and Wers-inger,1999;Roselli and Chambers,1999;Wersinger and Rissman,2000;Bakker et al.,2002).Intracellularly,es-trogen acts via one of two ER subtypes,?or?.Studies using ER?and ER?knockout mice indicate that the two subtypes may play different roles in the expression of male-typical behavior,with ER?acting to masculinize male behavior(Scordalakes et al.,2002;Scordalakes and Rissman,2004),whereas ER?may be involved in defem-inizing male behavior(Kudwa et al.,2005).These studies further support the hypothesis that changes in the expres-sion of ER?would alter the expression of masculine be-havior,permitting a greater expression of prosocial behav-ior.

Sexually dimorphic ER?and social behavior The results from this study and comparison of ER?between two behaviorally distinct populations of prairie voles(Cushing et al.,2004)indicate that a reduction in the occurrence of ER?is associated with increased expression of prosocial behavior.However,species differences in the level of ER?occur primarily in males.This suggests two things:?rst,that monogamy involves a greater change in male behavior than in female behavior and,second,that these changes resulted in increased sexual dimorphism in receptor expression.In rats and the polygynous voles ex-amined here,the expression and distribution of ER?in the brains of males and females are similar(Simmerly et al.,1990;Lauber et al.,1991;Kuhnemann et al.,1995; Yokosuka et al.,1997;Kawata et al.,1998;La?amme et al.,1998),especially in the BST and MeA.Taken together, these?ndings support a recent hypothesis that sexually dimorphic expression of receptor patterns may produce similar behavioral patterns,whereas similar patterns of receptors may produce sexually dimorphic behavior(De Vries and Villalba,1997).The basis of this hypothesis is that masculine behavioral patterns are established during development,perinatally and/or neonatally(Han and De Vries,2003).During development,males have higher lev-els of circulating steroids and aromatase activity.There-fore,during development,males have effectively higher levels of estrogen than females.This means that males with the same pattern of ER as females would be more affected by estrogen than females.If males have a reduc-tion in ER,then the masculinizing effects would be re-duced or eliminated,producing more female-like behav-iors.If this hypothesis is correct,then sexual differences in ER should exist during the developmental period.Re-sults from prairie voles support this prediction,in that ER?expression in the BST and MeA is sexually dimorphic prior to weaning(Yamamoto et al.,in press).Also,neona-tal castration of prairie voles signi?cantly increases ER?in adulthood,producing a pattern that is very similar to that observed in females(Cushing and Kramer,2005),and reduces male prosocial behavior(Cushing et al.,2003). Site-speci?c ER?-IR and the expression of

male social behavior

Given that estrogen is involved in the regulation of a variety of behavioral and physiological responses,it seems unlikely that the evolution of monogamy would be associ-ated with an overall reduction in ER?,insofar as this would alter behaviors and physiological responses not as-sociated with monogamous behavior.Instead,monogamy should be achieved through site-speci?c changes in re-gions of the brain that regulate af?liation and aggression. One of the primary neural circuits playing a critical role in regulating social/sociosexual interactions consists of the MeA,BST,MPOA,LS,and VMH(Newman,1999).Re-sults form the current study are consistent with previous ?ndings in prairie voles and suggest a role of the BST and MeA in regulating species differences in the expression of male prosocial behavior.In polygynous species,such as rats,mice,and hamsters,the BST and MeA regulate the expression of social preference,af?liation,and aggression (Newman,1999;Rasia-Filho et al.,2000;Ferguson et al., 2001).Therefore,a reduction in ER?in these regions would be predicted to alter the expression of these behav-iors.Male prairie voles,which are monogamous,express low levels of ER?in the BST and MeA(Hnatczuk et al., 1994;Cushing et al.,2004),and the BST and MeA have been shown to play a critical role in regulating parental behavior and aggression in prairie voles(Wang and De Vries,1993;De Vries and Villalba,1997;Wang et al., 1997).

Changes in the expression of ER?may be limited to the BST and MeA for several reasons.First,as stated above, these regions play a critical role in the expression of af?l-iation and aggression.Second,they receive direct input form the vomeronasal organ and the olfactory bulb,so that the response of these regions to initial olfactory stimulus could in turn regulate the overall response by directly or indirectly affecting the response of other portions of the neural circuit.Third,changes in the expression of other regions,such as the MPOA,might adversely impact other aspects of sociosexual behavior.For example,the MPOA plays a major role in reproduction and sexual behavior.A reduction in the sensitivity to estrogen in the MPOA might interfere with the expression of male reproductive

602 B.S.CUSHING AND K.E.WYNNE-EDWARDS

behavior,such as mounting or intromission.However,the MPOA,LS,and VMH do regulate sociosexual behavior, and it is possible that,in other species,differences in ER?in the MPOA or other portions of the sociosexual neural circuit may be correlated with differential expression of male social behavior.Finally,although everything was done to minimize the potential effects associated with species-speci?c responses to housing,acclimation of ani-mals,and similar reproductive status,there is still a pos-sibility that the expression of ER?was associated with differential response to the effects of the stress of housing.

ER?:microtines and dwarf hamsters

A comparison of the pattern of distribution of ER?-IR among the three species of voles reveals a signi?cant pattern and provides further support for a role of ER?in establishing male prosocial behavior associated with mo-nogamy.Species differences were observed only in males. Differences were limited to the BST and MeA,meaning that differences between highly social males and less so-cial males were observed only in regions that are associ-ated with the expression of af?liation and aggression(see above).Pine voles,which are socially monogamous,dis-played signi?cantly lower levels of ER?-IR than polygy-nous montane voles.The comparison of the expression of ER?in meadow voles with these two species is particu-larly relevant.Meadow voles have been classi?ed as po-lygynous,but there is evidence that the expression of male prosocial behavior is variable and that they can display parental behavior and reduced pup-directed aggression (McGuire,1988;Storey et al.,1994;Parker and Lee,2001), which are typically associated with monogamy.The pat-tern of the distribution of ER??ts with the intermediate pattern of social behavior of male meadow voles;ER?-IR expression in the BST and MeA is intermediate to that of montane and pine voles.This suggests that intermediate patterns may be involved in the expression of behavioral plasticity.This also may explain why meadow vole males treated with vasopressin display parental behavior, whereas central vasopressin does not affect af?liation in montane males(Young et al.,1999),despite the fact that both display the polygynous vasopressin receptor pattern (Insel and Shapiro,1992;Insel et al.,1994;Young et al., 1997).

Comparison of ER?in the two hamster species,paral-leling the social differences between meadow and pine voles,also supported the hypotheses.The sexually dimor-phic expression,low levels of ER?-IR in males in the BST and MeA,suggests the potential for high levels of af?lia-tive behavior in males of both species.Djungarian ham-sters are considered to display obligate social monogamy (Wynne-Edwards,1995),with the male playing an active role in care of the offspring,because his presence signi?-cantly increases the survival of his offspring(Walton and Wynne-Edwards;1998;Reburn and Wynne-Edwards, 1999;Jones and Wynne-Edwards,2000;McInroy et al., 2000).In contrast,male participation in Siberian ham-sters appears to be seasonal,with males found in the nest along with newborn pups late in the breeding season (Wynne-Edwards,1995).The expression of ER?in male Siberian hamsters may therefore re?ect the potential to express the prosocial behavior associated with facultative social monogamy.

Unlike most male rodents,Siberian and Djungarian males have high circulating levels of estrogen(Schum and Wynne-Edwards,2005).This suggests that the expression of prosocial behavior could be regulated through the in-teraction of ER?and estrogen levels,with circulating lev-els of estrogen potentially modulating the behavioral re-sponses of males.Because Djungarian males express very low levels of ER?in the MeA and BST,estrogen,even at high levels,may have a minimal effect on af?liation and aggression.In contrast,the higher expression of ER?in Siberian males could facilitate the expression of“male-typical”behavior rather than the more“feminized”paren-tal behaviors seen in Djungarian hamsters in response to high levels of estrogen.Differences in the BST may ex-plain differences in parental behavior,insofar as the BST has been shown to in?uence the expression of male paren-tal behavior(Wang and De Vries,1993;Bamshad et al., 1994).Thus,in the Siberian hamster,environmental or social conditions that reduced circulating levels of estro-gen could stimulate the facultative expression of prosocial behaviors,including paternal behaviors.

Differences in ER?expression in hamsters were not restricted to males.Female Siberian hamsters had higher expression of ER?-IR in the ARC than female Djungarian hamsters.Although the current study did not reveal between-species differences in female voles,there were signi?cant differences in ER?in the MPOA of females from two behaviorally distinct populations of prairie voles, with the less social females displaying higher levels of ER?-IR(Cushing et al.,2004).Differences in expression of ER?between females suggest the intriguing possibility that ER?could play a role in female regulation of paternal involvement.In meadow voles,the female is actively in-volved in determining whether males are allowed to enter the nest(Storey et al.,1994),and female Siberian ham-sters may be doing the same thing(Wynne-Edwards, 1995,2003).If females are determining whether the male is allowed to participate in caring for the young,then it is possible that females with higher levels of ER?would be less likely to allow males to enter the nest.This may also explain why Siberian hamsters displayed sexually dimor-phism in the ARC and VMH,in that the differences in these areas appear to be associated with higher levels of ER?-IR in females compared with Djungarian hamsters, rather than a decrease in males.The current results, showing hamster species differences,even among females, are likely to be related to differences between obligate and facultative social af?liation.

In conclusion,the results from this study provide fur-ther support for the hypothesis that ER?expression and thus estrogen play an important role in determining the expression of male behavior in microtines,with a reduc-tion in the expression of ER?in the MeA and/or the BST being associated with males of species that can dsiplay high levels of prosocial behavior.The fact that a similar pattern occurs in dwarf hamsters suggests that reduction of ER?in males may be associated with the evolution of social monogamy in rodents.Although we believe that changes in responses to estrogen are necessary for the expression of social monogamy,we are not proposing that changes in ER?alone are suf?cient to create social mo-nogamy.We believe that social monogamy is the result of the interaction of steroidal responses and neuropeptide regulation,speci?cally oxytocin and vasopressin.This view supports the recent proposal that social recognition is the product of a four-gene interaction involving ER, oxytocin,and oxytocin receptors(Choleris et al.,2003).

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ACKNOWLEDGMENTS

We thank Dr.Kristin Kramer and Nancy Cushing for their critical review of this article and Dr.Michael Ferkin (University of Memphis)and Dr.Nancy Solomon(Miami University of Ohio)for supplying voles for this study.

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香港中文大学2012-2013汉语语言学与语言习得专业ma笔试题

2012-13 CUHK Recruitment Test MA in Linguistics MA in Chinese Linguistics and Language Acquisition Name __________________________ Email __________________________ Phone __________________________ University __________________________ City __________________________ Province __________________________

Section One Answer all the questions in this section. Question 1 Analyze the following data and decide if [s] and [z] are allophones of the same phoneme or belong to different phonemes.

Look at the following data involving allomorphic variation: i.lokanta ‘a restaurant’lokantada ‘in/at a restaurant’ ii.kap?‘a door’kap?da ‘in/at a door’ iii.randevu ‘an appointment’randevuda ‘in/at an appointment’iv.ba?‘a head’ba?ta ‘in/at a head’ v.kitap ‘a book’kitapta ‘in/at a book’ vi.koltuk ‘an armchair’koltukta ‘in/at an armchair’ vii.taraf ‘a side’tarafta ‘in/at a side’ (note: ? is a high back unrounded vowel) (a) What kind of morphological means does this language employ to express the meaning ‘in/at’? (b) What are the allomorphs of this morpheme? (c) Describe their distribution in the data. (d) What phonological process is involved in such distribution? Question 3 What are the possible meanings of ‘unlearnable’ and ‘undoable’? Draw tree diagrams to explain their possible meanings.

通达信均线粘合选股公式

创作编号： GB8878185555334563BT9125XW 创作者：凤呜大王* 通达信均线选股指标公式 MA10:=MA(C,10); MA30:=MA(C,30); MA60:=MA(C,60); LL:=MIN(MIN(MA10,MA30),MA60); 选股:COUNT(MA30>REF(MA30,1),2)=2 AND MA60>REF(MA60,1) AND MA10=LL AND CROSS(C,MA10); 通达信均线粘合选股公式 MA1:=MA(CLOSE,5); MA2:=MA(CLOSE,10); MA3:=MA(CLOSE,20); MA4:=MA(CLOSE,60); MA5:=MA(CLOSE,120); MA6:=MA(CLOSE,250); A:MAX(MAX(MA1,MA2),MA3),LINETHICK0; B:MIN(MIN(MA1,MA2),MA3),LINETHICK0; 三线粘合:IF(RANGE(100*(A-B)/B,0,5),100*(A-B)/B,DRAWNULL),LINETHICK0; SA:MAX(MAX(MA1,MA2),MAX(MA3,MA4)),LINETHICK0; SB:MIN(MIN(MA1,MA2),MIN(MA3,MA4)),LINETHICK0; 成本价均线 AMOV:=VOL*(OPEN+CLOSE)/2; AMV1:SUM(AMOV,M1)/SUM(VOL,M1);

AMV2:SUM(AMOV,M2)/SUM(VOL,M2); AMV3:SUM(AMOV,M3)/SUM(VOL,M3); AMV4:SUM(AMOV,M4)/SUM(VOL,M4) AMOV:=VOL*(OPEN+CLOSE)/2; AMV1:SUM(AMOV,5)/SUM(VOL,5); AMV2:SUM(AMOV,13)/SUM(VOL,13); AMV3:SUM(AMOV,34)/SUM(VOL,34); AMV4:SUM(AMOV,60)/SUM(VOL,60); A:MAX(MAX(AMV1, AMV2), AMV3); B:MIN(MIN(AMV1, AMV2), AMV3); 三线粘合:IF(RANGE(100*(A-B)/B,0,5),100*(A-B)/B,DRAWNULL); SA:MAX(MAX(AMV1, AMV2),MAX(AMV3, AMV4)); SB:MIN(MIN(AMV1, AMV2)),MIN(AMV3, AMV4)); 创作编号： GB8878185555334563BT9125XW 创作者：凤呜大王*

托拉塞米片说明书

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