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.     

人为疼痛刺激下金色中仓鼠幼鼠叫声的发育过程

金色中仓鼠幼鼠可以利用可听声和超声信号与母鼠进行交流,这些声音可以反映个体的寒冷、饥饿、疼痛等不同生理状态和需求。因疼痛诱发的叫声对于维持幼鼠的存活也有着重要意义。本实验通过录制人为疼痛刺激下,不同日龄金色中仓鼠的叫声,分析并比较了5 - 30 日龄金色中仓鼠不同发声信号特征(可听声出现频次、可听声持续时程、可听声主频率、超声出现频次、超声持续时程、超声主频率)的性别差异;同时记录了幼鼠的两种发声随日龄的变化趋势。结果发现:幼鼠两种叫声的各种参数均未表现性二型现象。幼鼠超声发生频次随日龄增加而逐渐减少。而可听声却正相反,随日龄增加而逐渐上升,并在20 日龄时达到最高峰,之后逐渐下降。可听声持续时程也随日龄而增加。综上,在人为疼痛刺激下,随着日龄增加,幼鼠更倾向于使用可听 声而非超声与母兽进行交流。     

Characterizing maternal isolation-induced ultrasonic vocalizations in a gene–environment interaction rat model for autism

Deficits in social communication and language development belong to the earliest diagnostic criteria of autism spectrum disorders. Of the many risk factors for autism spectrum disorder, the contactin-associated protein-like 2 gene, CNTNAP2, is thought to be important for language development. The present study used a rat model to investigate the potential compounding effects of autism spectrum disorder risk gene mutation and environmental challenges, including breeding conditions or maternal immune activation during pregnancy, on early vocal communication in the offspring. Maternal isolation-induced ultrasonic vocalizations from Cntnap2 wildtype and knockout rats at selected postnatal days were analyzed for their acoustic, temporal and syntax characteristics. Cntnap2 knockout pups from heterozygous breeding showed normal numbers and largely similar temporal structures of ultrasonic vocalizations to wildtype controls, whereas both parameters were affected in homozygously bred knockouts. Homozygous breeding further exacerbated altered pitch and transitioning between call types found in Cntnap2 knockout pups from heterozygous breeding. In contrast, the effect of maternal immune activation on the offspring's vocal communication was confined to call type syntax, but left ultrasonic vocalization acoustic and temporal organization intact. Our results support the “double-hit hypothesis” of autism spectrum disorder risk gene–environment interactions and emphasize that complex features of vocal communication are a useful tool for identifying early autistic-like features in rodent models.     

Deficiency of the paternally inherited gene Magel2 alters the development of separation-induced vocalization and maternal behavior in mice

The behavior of offspring results from the combined expression of maternal and paternal genes. Genomic imprinting silences some genes in a parent-of-origin specific manner, a process that, among all animals, occurs only in mammals. How genomic imprinting affects the behavior of mammalian offspring, however, remains poorly understood. Here, we studied how the loss of the paternally inherited gene Magel2 in mouse pups affects the emission of separation-induced ultrasonic vocalizations (USV). Using quantitative analysis of more than 1000 USVs, we characterized the rate of vocalizations as well as their spectral features from postnatal days 6–12 (P6–P12), a critical phase of mouse development that covers the peak of vocal behavior in pups. Our analyses show that Magel2 deficient offspring emit separation-induced vocalizations at lower rates and with altered spectral features mainly at P8. We also show that dams display altered behavior towards their own Magel2 deficient offspring at this age. In a test to compare the retrieval of two pups, dams retrieve wildtype control pups first and faster than Magel2 deficient offspring. These results suggest that the loss of Magel2 impairs the expression of separation-induced vocalization in pups as well as maternal behavior at a specific age of postnatal development, both of which support the pups' growth and development.     

Prolactin levels and maternal behavior induced by ultrasonic vocalizations of the rat pup.

The relationship among ultrasonic vocalization (USV), prolactin and maternal behavior was investigated in lactating rat mothers and their pups. The lactating mother had a cannula inserted into the external jugular vein, and was exposed to USVs emitted from a pup immediately. Changes of prolactin and maternal behavior were determined. Prolactin increased dramatically during exposure to USVs, when maternal search, retrieving and nest building behavior appeared significantly. These results suggested that the relationship among USV, prolactin and maternal behavior was included in communication between lactating mother and pup.     

The effects of repeated early deprivation on ultrasonic vocalizations and ontogenetic development in mandarin vole pups

Early deprivation is popularly used in rodent models as an early life social stress to investigate and determine the factors that affect the development of the brain and behavior. Ultrasonic calls made by pups play an important role in parental–pup interactions during the neonatal period. However, whether repeated early deprivation affects the properties of ultrasonic vocalizations (USVs) produced by mandarin vole (Microtus mandarinus) pups, and whether ontogenetic development is subsequently affected, remains unclear. Here we measured USVs and developmental parameters in mandarin vole pups deprived of their parents and littermates for 3 h per day (ED, which is significantly different from 5 min isolation used to induce USVs) and another pup group developed under normal nest conditions (PC). Repeated measures analysis indicated that the number of USVs from ED pups was significantly lower than those from PC pups during the postnatal period (p < 0.05). The pulse durations of ED pups were longer than those of PC pups at two (p < 0.001) and five days of age (p < 0.05), but shorter at 14 days of age (p < 0.001). Compared with PC pups, the frequency range of the ED pups was wider at 18–45 kHZ, variable during the first week, smaller and narrower at 18–30 kHZ at eight and 11 days of age, and became stable similar to PC pups at 25 kHZ after 14 days of age. ED also reduced pup body weight significantly and resulted in earlier eye opening compared with PC pups (p < 0.001). A positive relationship was also found between USV emissions and levels of parental care received by pups. It appears that pup USVs are an important age-dependent behavioral phenotype and an effective communicative method between parents and offspring. Prolonged parental and littermate deprivation (ED) may alter USVs emitted by pups and then ontogenetic development and parental care. Mandarin voles show USV properties similar to socially monogamous rodents and this add further support to the hypothesis that species with different social systems produce different patterns of ultrasonic vocalizations. USVs, ontogenetic development and parental care are closely associated.     

Isolation calls and retrieving behavior in laboratory and wild-derived golden hamsters—No sign for inbreeding depression

Isolated juvenile golden hamsters produce ultrasonic and audible vocalizations, so-called isolation calls, as a reaction to being separated from their mother and nest and their cooling down. Their aim is to stimulate mothers to search and retrieve the pups. In this work, the vocalization of juvenile laboratory (Zoh:GOHA; Institute of Zoology, Martin-Luther-University Halle-Wittenberg) and juvenile wild-derived golden hamsters (captured in northern Syria and southern Turkey) from birth up to the age of 18 days were digitally recorded, analyzed and compared using an ultrasonic microphone and the software Avisoft. Furthermore, the retrieving behavior of the mothers was observed and compared. The results showed that the number of isolation calls was age-specific and the structure of the calls was influenced by body temperature, body mass and sex of the pups. The age of the pups determined retrieval by the maternal golden hamsters; however these did not discriminate between their own pups or foreign pups. In spite of enormous genetic differences between wild-derived and laboratory golden hamsters, only minor differences between the strains were found.     

Juvenile vocalizations ofCtenomys talarum (Rodentia: Octodontidae)

We analysed the physical structure and functional interpretation of juvenile vocalizations ofCtenomys talarum Thomas, 1898. Two sounds, one true vocalization (care-elicitation call) and one mechanical sound (nursing sound) were recorded during the nestling period. Care-elicitation calls were emitted by isolated pups and caused the mother to respond by immediately approaching the pups to take care of them. This maternal response to the care-elicitation calls ofC. talarum pups, together with the production of these vocalizations during the first weeks after birth, when pups depend exclusively on their mother to obtain food and maintain their body temperature, give preliminary support for the recent theory that care-elicitation cries are honest advertisements of offspring need.     

Dopamine receptor D2 deficiency reduces mouse pup ultrasonic vocalizations and maternal responsiveness

Dopamine signalling facilitates motivated behaviours, and the D2 dopamine receptor (D2R) is important in mother–infant interactions. D2R antagonists disrupt maternal behaviour and, in isolated rat pups, reduce ultrasonic vocalizations (USVs) that promote maternal interaction. Here, we examined the effects of genetic D2R signalling deficiency on pup‐dam interaction with Drd2 knockout (D2R KO) mice. Using heterozygous (HET) cross littermates, the effect of pup genotype on isolation‐induced USVs was quantified. Independent of parental genotype, D2R‐deficient pups emitted fewer USVs than wild type (WT) littermates in a gene dose‐dependent manner. Using reciprocal D2R KO‐WT crosses, we examined how parental genotype affects pup USVs. Heterozygous pups from D2R KO dams produced fewer USVs than HET pups from WT dams. Also, exposure to USV‐emitting pups increased plasma prolactin levels in WT dams but not in D2R KO dams, and KO dams showed delayed pup retrieval and nest building. These findings indicate the importance of the interaction between pup and dam genotypes on behaviour and further support the role of D2R signalling in maternal care.     

Comprehensive Analysis of Ultrasonic Vocalizations in a Mouse Model of Fragile X Syndrome Reveals Limited, Call Type Specific Deficits

Fragile X syndrome (FXS) is a well-recognized form of inherited mental retardation, caused by a mutation in the fragile X mental retardation 1 (Fmr1) gene. The gene is located on the long arm of the X chromosome and encodes fragile X mental retardation protein (FMRP). Absence of FMRP in fragile X patients as well as in Fmr1 knockout (KO) mice results, among other changes, in abnormal dendritic spine formation and altered synaptic plasticity in the neocortex and hippocampus. Clinical features of FXS include cognitive impairment, anxiety, abnormal social interaction, mental retardation, motor coordination and speech articulation deficits. Mouse pups generate ultrasonic vocalizations (USVs) when isolated from their mothers. Whether those social ultrasonic vocalizations are deficient in mouse models of FXS is unknown. Here we compared isolation-induced USVs generated by pups of Fmr1-KO mice with those of their wild type (WT) littermates. Though the total number of calls was not significantly different between genotypes, a detailed analysis of 10 different categories of calls revealed that loss of Fmr1 expression in mice causes limited and call-type specific deficits in ultrasonic vocalization: the carrier frequency of flat calls was higher, the percentage of downward calls was lower and that the frequency range of complex calls was wider in Fmr1-KO mice compared to their WT littermates.     

Chronic REM Sleep Restriction in Juvenile Male Rats Induces Anxiety-Like Behavior and Alters Monoamine Systems in the Amygdala and Hippocampus

Adolescence is marked by major physiological changes, including those in the sleep-wake cycle, such as phase delay, which may result in reduced sleep hours. Sleep restriction and/or deprivation in adult rats activate stress response and seem to be a risk factor for triggering emotional disorders. In the present study, we sought to evaluate the behavioral and neurobiological consequences of prolonged REM sleep restriction in juvenile male rats. Immediately after weaning, on postnatal day 21, three males from each litter were submitted to REM sleep deprivation and the other three animals were maintained in their home-cages. REM sleep restriction (REMSR) was accomplished by placing the animals in the modified multiple platform method for 18 h and 6 h in the home-cage, where they could sleep freely; the sleep restriction lasted 21 consecutive days, during which all animals were measured and weighed every 3 days. After the end of this period, all animals were allowed to sleep freely for 2 days, and then the behavioral tests were performed for evaluation of depressive and anxiety-like profiles (sucrose negative contrast test and elevated plus maze, EPM). Blood sampling was performed 5 min before and 30 and 60 min after the EPM for determination of corticosterone plasma levels. The adrenals were weighed and brains collected and dissected for monoamine levels and receptor protein expression. REMSR impaired the physical development of adolescents, persisting for a further week. Animals submitted to REMSR exhibited higher basal corticosterone levels and a greater anxiety index in the EPM, characteristic of an anxious profile. These animals also exhibited higher noradrenaline levels in the amygdala and ventral hippocampus, without any change in the expression of β1-adrenergic receptors, as well as higher serotonin and reduced turnover in the dorsal hippocampus, with diminished expression of 5-HT1_A. Finally, greater concentration of BDNF was observed in the dorsal hippocampus in chronically sleep-restricted animals. Chronic REMSR during puberty impaired physical development and induced anxiety-like behavior, attributed to increased noradrenaline and serotonin levels in the amygdala and hippocampus.     

Comparative study on isolation calls emitted from hamster pups.

Waveforms of isolation calls emitted from hamster pups, which were Syrian hamsters, Djungarian hamsters, and Chinese hamsters, were compared in a basic study on improving reproduction by decrease of cannibalism, because it was reported that maternal behavior was induced by isolation calls in rodents. Isolation calls of hamster pups, isolated from their mother and receiving cold stress, were collected by Real-Time Spectrogram (RTS), and calculated to spectrograms and power spectra by SIGNAL. Isolation calls consisted of ultrasonic vocalizations (USVs) and audible vocalizations (ADVs) in each species. Waveforms of isolation calls emitted by the hamster pups, were shown to have several characteristic features. In this study, the species specificity of isolation calls was shown in hamster pups. It would seem that the species specificity originates in the differences of sensitivity to cold stress via the autonomic nerve in hamsters.     

Discrimination of Ultrasonic Vocalizations by CBA/CaJ Mice (Mus musculus) Is Related to Spectrotemporal Dissimilarity of Vocalizations

The function of ultrasonic vocalizations (USVs) produced by mice (Mus musculus) is a topic of broad interest to many researchers. These USVs differ widely in spectrotemporal characteristics, suggesting different categories of vocalizations, although this has never been behaviorally demonstrated. Although electrophysiological studies indicate that neurons can discriminate among vocalizations at the level of the auditory midbrain, perceptual acuity for vocalizations has yet to be determined. Here, we trained CBA/CaJ mice using operant conditioning to discriminate between different vocalizations and between a spectrotemporally modified vocalization and its original version. Mice were able to discriminate between vocalization types and between manipulated vocalizations, with performance negatively correlating with spectrotemporal similarity. That is, discrimination performance was higher for dissimilar vocalizations and much lower for similar vocalizations. The behavioral data match previous neurophysiological results in the inferior colliculus (IC), using the same stimuli. These findings suggest that the different vocalizations could carry different meanings for the mice. Furthermore, the finding that behavioral discrimination matched neural discrimination in the IC suggests that the IC plays an important role in the perceptual discrimination of vocalizations.     

Subchronic 17alpha-ethinyl estradiol differentially affects subtypes of sleep and wakefulness in ovariectomized rats

In ovariectomized (OVX) Sprague-Dawley rats, estradiol benzoate (EB) has been reported to decrease rapid eye movement (REM) and non-REM (NREM) sleep during the dark phase for up to 3 days. It is unknown, however, if estrogenic effects on sleep extend beyond 3 days or if other estrogens could induce the same changes. Furthermore, it is unclear whether the increased wakefulness in the dark phase was due to changes in active or quiet wakefulness. Therefore, we examined the effects of daily injections of 17alpha-ethinyl estradiol (EE) for 6 days on sleep and wakefulness in the OVX rat. After 3 days of baseline recording using a telemetric system, rats were administered sesame oil (sc) for 3 days followed by injection with EE (20 mug/rat/day, sc) for 6 days. After treatment, sleep was recorded during hormone withdrawal for an additional 5 days. A few sporadic but statistically significant increases in light phase sleep occurred during the last 3 days of EE treatment. Starting on day 2 of the study, EE caused statistically significant decreases in dark phase REM sleep that were maintained throughout the treatment period and persisted until the 3rd day of hormone withdrawal. During the dark phase, statistically significant decreases in NREM sleep and increases in active wakefulness started on the second day of treatment and abated by the end of treatment. This study demonstrated that EE had similar effects on sleep-wakefulness to EB and demonstrates the utility of telemetric polysomnographic recording of the female OVX rat as a model for understanding the estrogen-induced changes on sleep-wakefulness.     

Ultrasonic isolation calls in genetically high- and low-emotional rat pups.

The present study was undertaken to investigate the relationship between the emotionality and the modulation of ultrasonic vocalizations in Tsukuba High Emotional (THE) and Tsukuba Low Emotional (TLE) strain rat pups 3-18 days old. The THE pups, while isolated from their dam and littermates and placed in a cold environment, emitted ultrasonic isolation calls at a high rate until day 15. In contrast, ultrasound production was at a consistently low level throughout the test period in the TLE pups. The ultrasonic isolation calls of THE pups were attenuated to the same level as those of the TLE pups after administration of diazepam (1 mg/kg, s.c.), a benzodiazepine receptor agonist, at 6 and 12 days of age. These findings suggest that the high emotionality of the rat pups was reflected largely by the emission of ultrasounds in response to isolation distress rather than the number of the benzodiazepine receptors in the brain that might play a role in physiologic mediation of the rat pup isolation call.     

Silent or Vocalizing Rats Copulate in a Similar Manner

Both male and female rats produce 50 kHz ultrasonic vocalizations (USVs) in the presence of a sexual partner and during copulation. Previous studies showed that USVs have no incentive value for rats. In this study, we evaluated the role of USVs in behavior during copulation. Three groups of rats were used: sham males paired with sham females, devocalized females paired with sham males, and sham females paired with devocalized males. During the copulation test, the USVs emitted by the sham rat were recorded and the sexual behavior of both the male and the female were observed. The results revealed that devocalized and sham females showed similar patterns of sexual behavior and no difference was found in the copulatory behavior of devocalized and sham males. Also the behavior of the partner of a sham rat was comparable to the partner of a devocalized rat. In addition, almost no changes in USVs emission were found in the 5 seconds before and/or after a copulatory behavior. It can be concluded that USVs play no important role in rat copulatory behavior at least in sexually naïve rats.     

Selection on ultrasonic call rate in neonatal rats affects low frequency,but not ultrasonic,vocalizations in adults

In this experiment, we studied a rodent model selected over 57 generations for high or low rates of ultrasonic vocalizations (USVs) during maternal separation as pups. We investigated the influence of this breeding on the adult animals’ subsequent vocal output, comparing acoustic variables across developmental stages. We hypothesized that selection on pup USV rate would impact adult USV production without affecting lower frequency calls. Contrary to this hypothesis, we found neither number of USV calls or other acoustic variables to differ among selected adult lines. Instead, we found that pup USV selection mainly affected adults’ low-frequency (human-audible) calls. Furthermore, low-frequency vocalizations did not fully fit a predicted correlation between body weight and fundamental frequency: high line males, although the heaviest on average, did not produce the lowest fundamental frequencies. Our findings suggest that selection for early ultrasonic vocal behaviour pleiotropically results in changes in anatomical production mechanisms and/or neural control affecting low-frequency calls.     

Phenomenology of rapid eye movement (REM) sleep behavior disorder in Parkinson’s disease: A descriptive study using the REM sleep behavior disorder severity scale (RBDSS)

Using the rapid eye movement (REM) sleep behavior disorder severity scale (RBDSS) as a reliable clinical tool we further assessed the phenomenology of REM sleep behavior disorder (RBD) in 56 Parkinson’s disease patients with RBD. The scale uses phenomenological categories based on the localization of movements in the distal or proximal extremities and/or involving the trunc and on the presence or absence of vocalizations. Interrater reliability has been published previously. In the current study we looked into the distribution of motor and vocal phenomena. We identified a small percentage of patients with only vocalizations (4/56), and 8/56 patients with and 10/56 patients without vocalizations and small nonviolent movements of the distal extremities or facial jerks. Ten patients showed more forceful movements of the proximal extremities, 11 patients with movements involving the proximal extremities had additional vocalizations, 5 patients were recorded with axial involvement, and 12 patients with axial movements and vocalizations. These findings underline the clinical variety of RBD manifestation in Parkinson’s disease patients without a certain pattern. However, both extreme variants, the mild one and the violent one, are rare. The RBDSS facilitates the risk estimate for harmful behaviors and may be recommended for comparative studies on RBD and its pharmacotherapy.

     

A comparative study of isolation-induced ultrasonic vocalization in rodent pups.

The purpose of this study was to determine whether species differences in neonatal vocalizations of rodent pups could be observed. Ultrasonic vocalizations of pups of 5 rodent species, mouse (ICR), vole (Microtus arvalis), Syrian hamster, rat (Wistar-Imamichi), and Mongolian gerbil were recorded from 3 to 15 or 21 days of age. Recordings were made under conditions of separation from mothers and litter mates in a cooled chamber (approximately 10 degrees C). The major species differences observed were age specific and species specific frequencies. The Mongolian gerbil displayed a different frequency change with age. Namely, the day on which ultrasonic vocalizations ceased was delayed in Mongolian gerbil compared with the other rodents. The modal peak frequencies of ultrasound emitted from pups at 3 days of age were low (around 35 kHz) in the vole and the Syrian hamster, medium (around 45 kHz) in the rat and the Mongolian gerbil, and high (around 55 kHz) in the mouse.