Vasopressin and aggression in cross-fostered California mice (Peromyscus californicus) and white-footed mice (Peromyscus leucopus)

To examine how developmental experiences alter neural pathways associated with adult social behavior, we cross-fostered pups between the more aggressive and monogamous California mouse (Peromyscus californicus) and the less aggressive and polygamous white-footed mouse (P. leucopus). Cross-fostered males became more like their foster parents when tested as adults. Male white-footed mice became more aggressive only in an aggression test in a neutral arena, whereas the territorial California mice became less aggressive in resident-intruder aggression test, as measured by attack latency. Only the species that displayed a change in resident-intruder aggression showed a change in arginine vasopressin (AVP) levels: cross-fostered California mice had significantly lower levels of AVP-immunoreactive (AVP-ir) staining than controls in the bed nucleus of the stria terminalis (BNST) and the supraoptic nucleus (SON) and a nonsignificant trend toward lower levels in the medial amygdala (MA). Neither species showed changes in AVP-ir staining in a control area, the paraventricular nucleus (PVN). The changes in AVP-ir staining in the BNST and SON may not be caused by stress because cross-fostering was not associated with changes in adult plasma concentrations of two steroid hormones, corticosterone and testosterone, that have been associated with stress-related alterations in AVP pathways. These results suggest that manipulating the early parental environment can directly alter both a neurotransmitter system and species-typical patterns of social behavior, but that these effects may vary between species and under different social contexts.     

Paternal experience and stress responses in California mice (Peromyscus californicus)

Paternal behavior greatly affects the survival, social development, and cognitive development of infants. Nevertheless, little research has been done to assess how paternal experience modifies the behavioral characteristics of fathers, including fear and stress responses to a novel environment. We investigated long-term behavioral and physiologic effects of parental experience in mice (Peromyscus californicus) and how this response activates the hypothalamic-pituitary-adrenal axis (as measured by corticosterone and dehydroepiandrosterone [DHEA] levels) and interacts with anxiety-related behaviors. Three groups of adult males were tested--fathers exposed to pups, virgins exposed to pups, and virgins never exposed to pups--in 2 environments designed to elicit anxiety response: an open field with a novel object placed in the center and a closed cage containing a sample of a component of fox feces. Behavioral responses were measured by using traditional methods (duration and frequency) and behavioral-chain sequences. Results indicated that paternal experience significantly modifies a male mouse's behavioral and physiologic responses to stress-provoking stimuli. Compared with inexperienced male mice, experienced male mice had a significant decrease in the occurrence of incomplete behavioral chains during the exposure to the novel object, an index of reduced stress. Further, even moderate pup exposure induced behavioral modifications in virgin male mice. These behavioral responses were correlated with changes in corticosterone and DHEA levels. Together, these data provide evidence that interactions between male mice and offspring may have mutually beneficial long-term behavioral and physiologic effects.     

Ultrasonic vocalizations and ontogenetic development in California mice (Peromyscus californicus)

This experiment investigated the time-course of behavioral and physical development in 18 male and 18 female pups from 18 litters of California mice. From 1 to 23 days of age animals were observed for a 6-min observation period every other day, followed by a neurobehavioral testing session. Ultrasonic vocalizations (UVs), coordinated movements, neuromotor indicators and physical parameters were measured. The production of UVs peaked during the first week of development, remained stable from 9 to 15 days of age, and decreased abruptly thereafter. Females vocalized more than males during the first 9 days after birth, although this difference only was statistically significant on the third day. There was an inverse relationship between the emission of UVs and coordinated movements. The frequency of UVs dropped significantly 1 day after the pups had displayed surface righting, were able to hear, and had begun opening their eyes compared with 1 day before. In conclusion, it appears that there is a sex difference in the emission of UVs, which is more intense at the beginning of development. Furthermore, the ontogenetic patterns of changes in the emission of UVs, by both males and females in California mice, are inversely related to the development of coordinated movements, such as rearing, locomotion and self-grooming.     

Acute effects of corticosterone injection on paternal behavior in California mouse (Peromyscus californicus) fathers

Glucocorticoids are thought to mediate the disruption of parental behavior in response to acute and chronic stress. Previous research supports their role in chronic stress; however, no study has experimentally tested the effects of acute glucocorticoid elevation on paternal behavior. We tested the prediction that acute corticosterone (CORT) increases would decrease paternal behavior in California mouse fathers and would lead to longer-term effects on reproductive success, as even short-term increases in CORT have been shown to produce lasting effects on the hypothalamic-pituitary-adrenal axis. First-time fathers were injected with 30 mg/kg CORT, 60 mg/kg CORT or vehicle, or left unmanipulated. Interactions between the male and its pup(s) were recorded 1.5–2 h after injection and scored for paternal and non-paternal behavior. Treatment groups were combined into control (unmanipulated + vehicle, n = 15) and CORT (30 mg/kg + 60 mg/kg, n = 16) for analysis based on resulting plasma CORT concentrations. CORT treatment did not alter paternal or non-paternal behaviors or any long-term measures (male body mass or temperature, pup growth rate, pup survival, interbirth interval, number or mass of pups born in the second litter). Fathers showed a significant rise in body mass at day 30 postpartum, followed by a decrease in body mass after the birth of the second litter; however, this pattern did not differ between the CORT and control groups. In summary, acute elevation of plasma CORT did not alter direct paternal behavior, body mass, or reproductive outcomes, suggesting that acute CORT elevation alone does not overtly disrupt paternal care in this biparental mammal.     

Testosterone, paternal behavior, and aggression in the monogamous California mouse (Peromyscus californicus)

Testosterone (T) mediates a trade-off, or negative correlation, between paternal behavior and aggression in several seasonally breeding avian species. However, the presence or absence of a T-mediated trade-off in mammals has received less attention. We examined the relationship between paternal behavior and territorial aggression in the biparental California mouse, Peromyscus californicus. In contrast to seasonally breeding birds, T maintains paternal behavior in this year-round territorial species. Castration reduced paternal behavior, whereas T replacement maintained high levels of paternal behavior. We hypothesize that T is aromatized in the brain to estradiol, which in turn stimulates paternal behavior. In contrast to paternal behavior, aggressive behavior was not reduced by castration. Interestingly, only sham males showed an increase in aggression across three aggression tests, while no change was detected in castrated or T-replacement males. Overall, trade-offs between aggression and paternal behavior do not appear to occur in this species. Measures of paternal behavior and aggression in a correlational experiment were actually positively correlated. Our data suggest that it may be worth reexamining the role that T plays in regulating mammalian paternal behavior.     

Acute effects of corticosterone injection on paternal behavior in California mouse (Peromyscus californicus) fathers

Glucocorticoids are thought to mediate the disruption of parental behavior in response to acute and chronic stress. Previous research supports their role in chronic stress; however, no study has experimentally tested the effects of acute glucocorticoid elevation on paternal behavior. We tested the prediction that acute corticosterone (CORT) increases would decrease paternal behavior in California mouse fathers and would lead to longer-term effects on reproductive success, as even short-term increases in CORT have been shown to produce lasting effects on the hypothalamic-pituitary-adrenal axis. First-time fathers were injected with 30 mg/kg CORT, 60 mg/kg CORT or vehicle, or left unmanipulated. Interactions between the male and its pup(s) were recorded 1.5–2 h after injection and scored for paternal and non-paternal behavior. Treatment groups were combined into control (unmanipulated + vehicle, n = 15) and CORT (30 mg/kg + 60 mg/kg, n = 16) for analysis based on resulting plasma CORT concentrations. CORT treatment did not alter paternal or non-paternal behaviors or any long-term measures (male body mass or temperature, pup growth rate, pup survival, interbirth interval, number or mass of pups born in the second litter). Fathers showed a significant rise in body mass at day 30 postpartum, followed by a decrease in body mass after the birth of the second litter; however, this pattern did not differ between the CORT and control groups. In summary, acute elevation of plasma CORT did not alter direct paternal behavior, body mass, or reproductive outcomes, suggesting that acute CORT elevation alone does not overtly disrupt paternal care in this biparental mammal.     

Prolactin and paternal behavior in the biparental California mouse, Peromyscus californicus

Relatively little is known about hormonal mechanisms underlying paternal behavior in mammals. Male California mice, Peromyscus californicus, display extensive parental care toward their young. Parental behavior of fathers, expectant fathers (males living with their pregnant partner), and virgin males was assessed in a 10-min test with a 1- to 3-day-old alien pup. Few virgin males acted parental (19%) compared to fathers one day postpartum (80%) and expectant fathers (56%). Plasma prolactin levels were significantly elevated in fathers 2 days postpartum compared to expectant fathers and virgin males. Paternal prolactin levels were similar to those of mothers. There were no differences between groups in levels of plasma testosterone. These data suggest, contrary to other reports, that prolactin is a likely correlate of paternal behavior in rodents.     

Effect of neonatal handling and paternal care on offspring cognitive development in the monogamous California mouse (Peromyscus californicus)

In the laboratory rat and mouse, neonatal handling enhances hippocampal-dependent learning in adulthood, an effect mediated by changes in maternal behavior toward the handled young. In the present study, we examined the interaction between neonatal handling and biparental care during the early postnatal period and its effect on cognitive function in adult California mice (Peromyscus californicus). We characterized the parental behavior of handled and nonhandled father-present and father-absent families over the first 15 days of life. We then assessed cognitive performance of male and female offspring in the Barnes maze and object recognition test after they were 60 days of age. We found that the amount of licking and grooming received by pups was decreased in father-absent families. By postnatal days 12-15, licking and grooming in handled, father-absent families were equivalent to that of nonhandled, father-present families. Handling enhanced novel object recognition in father-present male mice with no effect in females. In the nonhandled group, the presence of the father had no effect on object recognition learning in male or female mice. Handling also enhanced spatial learning in the Barnes maze. In nonhandled families, the presence of the father appeared to have no effect on spatial learning in the male offspring. Interestingly, spatial learning in nonhandled, father-absent, female offspring was similar to that of handled animals. The average amount of licking and grooming received by pups was negatively correlated with the average number of errors made on the first day of reversal training in the Barnes maze. These data support previous findings that neonatal handling facilitates learning and memory in adulthood, suggest that under certain environmental conditions, there is a sex difference in the response of pups to paternal care, and further demonstrate the importance of active parental investment for offspring cognitive development.     

Sex differences in offspring discrimination in the biparental California mouse (Peromyscus californicus)

Journal of Ethology - Costs of parental care can include increased physical, physiological, and behavioral demands and reduced prospects for future reproduction. Therefore, animals may benefit from...     

Heritable, diet-induced hyperlipidemia in California mice (Peromyscus californicus) is due to increased hepatic secretion of very low density lipoprotein triacylglycerol

California mice (Peromyscus californicus) develop type II diabetes mellitus when fed a high-fat diet. We undertook the current studies to determine whether hyperlipidemia precedes the development of insulin resistance and to establish breeding colonies of hyperlipidemic and normolipidemic mice. For 6 wk, mice (n = 24) received a diet containing 25.8% of energy from fat. Mice representing the upper and lower quartiles of serum triacylglycerol (TAG) response (mean, >1000 mg/dl versus <300 mg/dl, respectively; 6 mice per group) were designated as high (HR) and low (LR) responders, respectively, and were used for further study. After 12 wk of consuming the high-fat diet, HR mice remained hypertriglyceridemic and developed hyperinsulinemia (5.1 +/- 1.3 ng/ml), hypercholesterolemia (309.3 +/- 31.0 mg/dl), and hyperglycemia (205.9 +/- 30.3 mg/dl) compared with LR mice. HR mice were not hyperphagic or obese. Offspring of HR x HR mice had elevated serum TAG concentrations (mean, 1752.2 +/- 209.7 mg/dl), hypercholesterolemia, hyperinsulinemia, and mild hyperglycemia by 5.5 mo of age. Mating HR male and LR female mice produced HR, intermediate, and LR progeny. HR mice had elevated serum concentrations of cholesterol, and plasma concentrations of high density lipoprotein cholesterol, and the very low density lipoprotein TAG compared with LR mice. Lipoprotein lipase and hepatic lipase activities did not differ between HR and LR mice. Studies of in vivo hepatic TAG production indicated that the hyperlipidemia of HR mice is a consequence of TAG hypersecretion.     

Sex differences in ultrasonic vocalizations and coordinated movement in the California mouse (Peromyscus californicus)

Geyer [Am. Zool. 21 (1981) 117] hypothesized that infant rodents increased the number of ultrasonic vocalizations when they moved in and out of the nest in order to elicit extended care from parents. We tested these hypotheses by recording ultrasonic vocalizations (USVs) and coordinated movements (locomotion and grooming) in California mouse and by recording USVs from pups before and after their parents retrieved them. In Experiment 1, USVs and coordinated movements were recorded from 2 to 30 days of age, in female and male Peromyscus californicus pups. USVs at 37, 42, 47, and 52kHz were digitized and recorded by computer and an event recorder program which was simultaneously used to record coordinated movement. Vocalizations persisted to 30 days of age. Vocalizations increased for both males and females after they spent more than 180s in coordinated movement and females vocalized more than males. Females also displayed more coordinated movement and earlier development of coordinated movement than males. There was no effect of litter size on USVs. In Experiment 2, the number of USVs emitted by pups and the latency of dams and sires to contact their pups and retrieve them was measured. There was no significant correlation between the number of USVs emitted by pups and the latency for a parent to contact or retrieve a pup. Results from Experiment 1 provided some support for Geyer's (1981) hypothesis and results from Experiment 2 did not support the hypothesis that the main function of USVs in California mouse pups was to elicit parental care.     

Effects of repeated pup exposure on behavioral,neural, and adrenocortical responses to pups in male California mice (Peromyscus californicus)

In biparental mammals, the factors facilitating the onset of male parental behavior are not well understood. While hormonal changes in fathers may play a role, prior experience with pups has also been implicated. We evaluated effects of prior exposure to pups on paternal responsiveness in the biparental California mouse (Peromyscus californicus). We analyzed behavioral, neural, and corticosterone responses to pups in adult virgin males that were interacting with a pup for the first time, adult virgin males that had been exposed to pups 3 times for 20 min each in the previous week, and new fathers. Control groups of virgins were similarly tested with a novel object (marble). Previous exposure to pups decreased virgins' latency to approach pups and initiate paternal care, and increased time spent in paternal care. Responses to pups did not differ between virgins with repeated exposure to pups and new fathers. In contrast, repeated exposure to a marble had no effects. Neither basal corticosterone levels nor corticosterone levels following acute pup or marble exposure differed among groups. Finally, Fos expression in the medial preoptic area, ventral and dorsal bed nucleus of the stria terminalis was higher following exposure to a pup than to a marble. Fos expression was not, however, affected by previous exposure to these stimuli. These results suggest that previous experience with pups can facilitate the onset of parental behavior in male California mice, similar to findings in female rodents, and that this effect is not associated with a general reduction in neophobia.     

Developmental plasticity in aerobic performance in deer mice (Peromyscus maniculatus)

While several studies have examined the abiotic effects of altitude (low ambient temperatures and hypoxia) on the aerobic performance of small mammals, few have explored the effects of development and maturation at different altitudes on aerobic performance as adults. We examined the basal metabolism and aerobic performance of deer mice (Peromyscus maniculatus) under four different developmental and testing regimes: (1) reared (gestation through weaning) and tested at high altitude; (2) reared and tested at low altitude; (3) reared at low altitude and tested at high altitude after acclimation; and (4) reared at low altitude and tested in hypoxia without acclimation. We found that mice that developed and were tested at low altitudes had a higher aerobic capacity (both aerobic performance and basal metabolic rate) than those that developed, or were acclimated as adults, at high altitudes. In addition, we found that mice that developed at high altitude did not have a higher aerobic capacity than those that developed at low altitude and were acclimated to high altitude as adults. Both groups tested at high altitudes had higher hematocrits (% red blood cells) and hemoglobin than mice tested at low altitudes. Surprisingly, mice acclimated to low altitudes and given an instantaneous exposure to hypoxia did not suffer a depression in aerobic performance.     

The Pox in the North American Backyard: Volepox Virus Pathogenesis in California Mice (Peromyscus californicus)

Volepox virus (VPXV) was first isolated in 1985 from a hind foot scab of an otherwise healthy California vole (Microtus californicus). Subsequent surveys in San Mateo County, CA, revealed serological evidence suggesting that VPXV is endemic to this area, and a second viral isolate from a Pinyon mouse (Peromyscus truei) was collected in 1988. Since then, few studies have been conducted regarding the ecology, pathology, and pathogenicity of VPXV, and its prevalence and role as a potential zoonotic agent remain unknown. To increase our understanding of VPXV disease progression, we challenged 24 California mice (Peromyscus californicus) intranasally with 1.6×10(3) PFU of purified VPXV. By day five post infection (pi) we observed decreased activity level, conjunctivitis, ruffled hair, skin lesions, facial edema, and crusty noses. A mortality rate of 54% was noted by day eight pi. In addition, internal organ necrosis and hemorrhages were observed during necropsy of deceased or euthanized animals. Viral loads in tissues (brain, gonad, kidney, liver, lung, spleen, submandibular lymph node, and adrenal gland), bodily secretions (saliva, and tears), and excretions (urine, and/or feces) were evaluated and compared using real time-PCR and tissue culture. Viral loads measured as high as 2×10(9) PFU/mL in some organs. Our results suggest that VPXV can cause extreme morbidity and mortality within rodent populations sympatric with the known VPXV reservoirs.     

Social and physical environments as a source of individual variation in the rewarding effects of testosterone in male California mice (Peromyscus californicus)

Despite extensive research revealing the occurrence of testosterone (T) pulses following social encounters, it is unclear how they lead to varied behavioral responses. We investigated the influence of residency (home versus unfamiliar environment) and social/sexual experience (pair-bonded, isolated or housed with siblings) on the plasticity of T's rewarding effects by measuring the development of conditioned place preferences (CPPs), a classical paradigm used to measure the rewarding properties of drugs. For pair-bonded males, T-induced CPPs were only produced in the environment wherein the social/sexual experience was accrued and residency status had been achieved. For isolated males, the T-induced CPPs only occurred when the environment was unfamiliar. For males housed with a male sibling, the T-induced CPPs were prevented in both the home and unfamiliar chambers. Our results reveal the plasticity of T's rewarding effects, and suggest that the behavioral functions of T-pulses can vary based on social/sexual experience and the environment in which residency was established. The formation of CPPs or reward-like properties of drugs and natural compounds can therefore exhibit malleability based on past experience and the current environment.     

Sex differences in social interaction behavior following social defeat stress in the monogamous California mouse (Peromyscus californicus)

Stressful life experiences are known to be a precipitating factor for many mental disorders. The social defeat model induces behavioral responses in rodents (e.g. reduced social interaction) that are similar to behavioral patterns associated with mood disorders. The model has contributed to the discovery of novel mechanisms regulating behavioral responses to stress, but its utility has been largely limited to males. This is disadvantageous because most mood disorders have a higher incidence in women versus men. Male and female California mice (Peromyscus californicus) aggressively defend territories, which allowed us to observe the effects of social defeat in both sexes. In two experiments, mice were exposed to three social defeat or control episodes. Mice were then behaviorally phenotyped, and indirect markers of brain activity and corticosterone responses to a novel social stimulus were assessed. Sex differences in behavioral responses to social stress were long lasting (4 wks). Social defeat reduced social interaction responses in females but not males. In females, social defeat induced an increase in the number of phosphorylated CREB positive cells in the nucleus accumbens shell after exposure to a novel social stimulus. This effect of defeat was not observed in males. The effects of defeat in females were limited to social contexts, as there were no differences in exploratory behavior in the open field or light-dark box test. These data suggest that California mice could be a useful model for studying sex differences in behavioral responses to stress, particularly in neurobiological mechanisms that are involved with the regulation of social behavior.