Pup Ultrasonic Vocalizations Research Articles

Perinatal high‐fat diet impairs pup retrieval and induces sex‐specific changes in ultrasonic vocalization characteristics of rat pups

Rodent pups emit ultrasonic vocalizations (USVs) to solicit maternal behavior, promoting their survival. Conversely, maternal behaviors affect the expression of pup USVs. We previously demonstrated that a maternal diet high in saturated fat (HFD) alters maternal behavior and is associated with early maturation of pups and their stress physiology. Here, we assessed the developmental profiles of pup USVs using quantitative and qualitative measures on postnatal days (PND)7 and 13. Quantitative measures included call counts, duration, and frequency, while qualitative measures examined calls' sonographic structures. HFD offspring lacked the typical decrease in USV numbers with age observed among control offspring. They also had shorter calls at PND7 compared to control and HFD offspring at PND13. HFD female offspring showed a greater number of one-frequency-sweep calls, while male pups showed a greater number of two-frequency-sweep calls compared to control offspring. Concomitantly, HFD dams showed impaired pup retrieval on PND7. The data suggest that fewer USVs of shorter duration in HFD offspring may alter dam solicitation and thus impair maternal pup retrieval. This study highlights the impacts of perinatal HFD exposure on the dyadic reciprocal interaction between dam and pups, which may set the stage for long-lasting effects on offspring physiology and behavior.

Ultrasonic vocalization of pup and adult fat-tailed gerbils (Pachyuromys duprasi).

Ultrasonic vocalizations (USVs) of laboratory rodents indicate animal emotional arousal and may serve as models of human disorders. We analysed spectrographically USV calls of pup and adult fat-tailed gerbils Pachyuromys duprasi during 420-s tests, including isolation, touch and handling. Based on combination of six different USV syllable contour shapes and six different note compositions, we classified 782 USV syllables of 24 pups aged 5–10 days to 18 types and 232 syllables of 7 adults to 24 types. Pups and adults shared 16 of these 26 USV types. Percentages of USV syllables with certain contour shapes differed between pups and adults. The contour shape and note composition significantly affected most acoustic variables of USV syllables in either pups or adults. The 1-note USV syllables were most common in either pups or adults. Pup USV syllables were overall longer and higher-frequency than adult ones, reminiscent of the USV ontogenetic pathway of bats and distinctive to rats and mice. We discuss that the USV syllable types of fat-tailed gerbils were generally similar in contour shapes and note compositions with USV syllable types of mice and rats, what means that software developed for automated classifying of mice ultrasound might be easily adapted or re-tuned to gerbil USV calls. However, using fat-tailed gerbils as model for biomedical research including control of USV vocalization is only possible since 6th day of pup life, because of the delayed emergence of USV calls in ontogeny of this species.

Temporal Association Cortex - A Cortical Hub for Processing Infant Vocalizations

Social interactions are mediated by sensory perception and action. Mother-infant bonding is an interaction that rapidly develops following parturition. We studied how ultrasonic vocalizations (USVs) are represented in the brain of mothers, as they start caring for their newborn pups. Using a combination of anatomical, chemogenetic, and electrophysiological techniques, we found an area associated with maternal plasticity in a high-order cortical region - the temporal association cortex (TeA). Monosynaptic connections into TeA come from diverse input sources, both cortically and subcortically. Further, we identified a circuit connecting USV-responsive neurons from primary auditory cortex to TeA. Silencing USV-responsive neurons in the A1-TeA circuit impairs auditory-driven maternal choices towards pup calls, and mothers show a unique pattern of plasticity in TeA. TeA neurons become decorrelated in mothers, improving the detection of pup USVs in TeA. We thus suggest that TeA is a hub of plasticity for auditory-driven social cues.

Subjecting Dams to Early Life Stress and Perinatal Fluoxetine Treatment Differentially Alters Social Behavior in Young and Adult Rat Offspring.

Recently, the putative association between selective serotonin reuptake inhibitor (SSRI) exposure during pregnancy and the development of social disorders in children has gained increased attention. However, clinical studies struggle with the confounding effects of maternal depression typically co-occurring with antidepressant treatment. Furthermore, preclinical studies using an animal model of maternal depression to study effects of perinatal SSRI exposure on offspring social behavior are limited. Therefore, the aim of this study was to investigate effects of perinatal fluoxetine exposure on juvenile and adult social behavior in male and female rat offspring, using an animal model of maternal vulnerability. We exposed heterozygous serotonin transporter (SERT) deficient female rats to early life maternal separation stress, and used this as a model for maternal vulnerability. Control and early life stressed heterozygous serotonin transporter knockout (SERT) dams were treated with the SSRI fluoxetine or vehicle throughout gestation and lactation. Subsequently, both male and female wildtype (SERT+/+) and heterozygous (SERT+/-) rat offspring were tested for pup ultrasonic vocalizations (USVs), juvenile social play behavior and adult social interaction. Fluoxetine treatment of the dams resulted in a reduced total USV duration in pups at postnatal day 6, especially in SERT+/+ males. Perinatal fluoxetine exposure lowered social play behavior in male offspring from both control and early life stressed dams. However, in females a fluoxetine-induced reduction in juvenile play behavior was only present in offspring from control dams. Offspring genotype did not affect juvenile play behavior. Despite fluoxetine-induced behavioral effects at juvenile age, fluoxetine reduced male adult social behavior in offspring from control dams only. Effects of fluoxetine on female adult social behavior were virtually absent. Interestingly, early life stress in dams increased adult social exploration in vehicle exposed SERT+/+ female offspring and total social behavior in fluoxetine exposed adult SERT+/- male offspring. Furthermore, SERT+/- males appeared less social during adulthood compared to SERT+/+ males. Overall, the present study shows that chronic blockade of the serotonin transporter by fluoxetine during early development has a considerable impact on pup USVs, juvenile social play behavior in both male and female offspring, and to a lesser extent on male social interaction in adulthood.

Oxytocin receptor knockout prairie voles generated by CRISPR/Cas9 editing show reduced preference for social novelty and exaggerated repetitive behaviors

Behavioral neuroendocrinology has benefited tremendously from the use of a wide range of model organisms that are ideally suited for particular questions. However, in recent years the ability to manipulate the genomes of laboratory strains of mice has led to rapid advances in our understanding of the role of specific genes, circuits and neural populations in regulating behavior. While genome manipulation in mice has been a boon for behavioral neuroscience, the intensive focus on the mouse restricts the diversity in behavioral questions that can be investigated using state-of-the-art techniques. The CRISPR/Cas9 system has great potential for efficiently generating mutants in non-traditional animal models and consequently to reinvigorate comparative behavioral neuroendocrinology. Here we describe the efficient generation of oxytocin receptor (Oxtr) mutant prairie voles (Microtus ochrogaster) using the CRISPR/Cas9 system, and describe initial behavioral phenotyping focusing on behaviors relevant to autism. Oxtr mutant male voles show no disruption in pup ultrasonic vocalization, anxiety as measured by the open field test, alloparental behavior, or sociability in the three chamber test. Mutants did however show a modest elevation in repetitive behavior in the marble burying test, and an impairment in preference for social novelty. The ability to efficiently generate targeted mutations in the prairie vole genome will greatly expand the utility of this model organism for discovering the genetic and circuit mechanisms underlying complex social behaviors, and serves as a proof of principle for expanding this approach to other non-traditional model organisms.

Examining the Reversibility of Long-Term Behavioral Disruptions in Progeny of Maternal SSRI Exposure.

Serotonergic dysregulation is implicated in numerous psychiatric disorders. Serotonin plays widespread trophic roles during neurodevelopment; thus perturbations to this system during development may increase risk for neurodevelopmental disorders. Epidemiological studies have examined association between selective serotonin reuptake inhibitor (SSRI) treatment during pregnancy and increased autism spectrum disorder (ASD) risk in offspring. It is unclear from these studies whether ASD susceptibility is purely related to maternal psychiatric diagnosis, or if treatment poses additional risk. We sought to determine whether maternal SSRI treatment alone or in combination with genetically vulnerable background was sufficient to induce offspring behavior disruptions relevant to ASD. We exposed C57BL/6J or Celf6+/- mouse dams to fluoxetine (FLX) during different periods of gestation and lactation and characterized offspring on tasks assessing social communicative interaction and repetitive behavior patterns including sensory sensitivities. We demonstrate robust reductions in pup ultrasonic vocalizations (USVs) and alterations in social hierarchy behaviors, as well as perseverative behaviors and tactile hypersensitivity. Celf6 mutant mice demonstrate social communicative deficits and perseverative behaviors, without further interaction with FLX. FLX re-exposure in adulthood ameliorates the tactile hypersensitivity yet exacerbates the dominance phenotype. This suggests acute deficiencies in serotonin levels likely underlie the abnormal responses to sensory stimuli, while the social alterations are instead due to altered development of social circuits. These findings indicate maternal FLX treatment, independent of maternal stress, can induce behavioral disruptions in mammalian offspring, thus contributing to our understanding of the developmental role of the serotonin system and the possible risks to offspring of SSRI treatment during pregnancy.

Genetic tagging of active neurons in auditory cortex reveals maternal plasticity of coding ultrasonic vocalizations

Cortical neurons are often functionally heterogeneous even for molecularly defined subtypes. In sensory cortices, physiological responses to natural stimuli can be sparse and vary widely even for neighboring neurons. It is thus difficult to parse out circuits that encode specific stimuli for further experimentation. Here, we report the development of a Cre-reporter mouse that allows recombination for cellular labeling and genetic manipulation, and use it with an activity-dependent Fos-CreERT2 driver to identify functionally active circuits in the auditory cortex. In vivo targeted patch recordings validate our method for neurons responding to physiologically relevant natural sounds such as pup wriggling calls and ultrasonic vocalizations (USVs). Using this system to investigate cortical responses in postpartum mothers, we find a transient recruitment of neurons highly responsive to USVs. This subpopulation of neurons has distinct physiological properties that improve the coding efficiency for pup USV calls, implicating it as a unique signature in parental plasticity.

Ultrasonic communication in rats: appetitive 50-kHz ultrasonic vocalizations as social contact calls

Rats are highly social animals, with a rich social behavioral repertoire, including the emission of so-called ultrasonic vocalizations (USV). Typically, three main types of USV can be distinguished based on a number of acoustic features, such as call duration, peak frequency, and frequency modulation: (I) isolation-induced 40-kHz USV in pups, as well as (II) aversive 22-kHz USV and (III) appetitive 50-kHz USV in juvenile and adult rats. In this review, evidence from selective breeding, devocalization, and playback studies is summarized and discussed, and it is concluded that appetitive 50-kHz USV serve as situation-dependent socio-affective signals with important communicative functions, for instance as play signals and/or social contact calls.

Effects of maternal or paternal bisphenol A exposure on offspring behavior

Bisphenol A (BPA) is an endocrine disrupting chemical used in the production of polycarbonate plastics and resins. Exposure to BPA during gestation has been proposed as a risk factor for the development of neurobehavioral disorders, such as autism spectrum disorder. To address the behavioral impact of developmental exposure to BPA, we tested offspring of mice exposed to a daily low dose of BPA during pregnancy. We also asked if preconception exposure of the sire affected behaviors in offspring. Sires that consumed BPA for 50days prior to mating weighed less than controls, but no effects on any reproductive measures were noted. Juvenile offspring exposed to BPA maternally, but not paternally, spent less time in the open arms of the elevated plus maze than controls, indicating increased anxiety-like behavior. However, neither parental exposure group differed significantly from controls in the social recognition task. We also assessed the behaviors of maternally exposed offspring in two novel tasks: ultrasonic vocalizations (USVs) in pups and operant reversal learning in adults. Maternal BPA exposure increased the duration and median frequency of USVs emitted by pups during maternal separation. In the reversal learning task, females responded more accurately and earned more rewards than males. Additionally, control females received more rewards than BPA females during the acquisition phase of the task. These are among the first studies conducted to ask if BPA exposure via the sire affects offspring behavior and the first study to report effects of gestational BPA exposure on pup USVs and adult operant responding.

Characterization of early communicative behavior in mouse models of neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a common neurogenetic disorder caused by mutation of the NF1 gene, in which 80% of affected children exhibit cognitive and behavioral issues. Based on emerging evidence that NF1 may be an autism predisposition gene, we examined autism spectrum disorder (ASD)-relevant early communicative behavior in Nf1 mouse models and observed alterations in both models. The changes in early communicative behavior in Nf1 mutant mice should motivate further studies into the causative factors and potential treatments for ASD arising in the context of NF1.

Does Size Really Matter? The Role of Tonotopic Map Area Dynamics for Sound Learning in Mouse Auditory Cortex.

This commentary centers on the novel findings by Shepard et al. (2016) published in eNeuro. The authors interrogated tonotopic map dynamics in auditory cortex (ACtx) by employing a natural sound-learning paradigm, where mothers learn the importance of pup ultrasonic vocalizations (USVs), allowing Shepard et al. to probe the role of map area expansion for auditory learning. They demonstrate that auditory learning in this paradigm does not rely on map expansion but is facilitated by increased inhibition of neurons tuned to low-frequency sounds. Here, we discuss the findings in light of the emerging enthusiasm for cortical inhibitory interneurons for circuit function and hypothesize how a particular interneuron type might be causally involved for the intriguing results obtained by Shepard et al.

M9 - Sex-Specific Foxp1 And Foxp2 Expression In The Developing Mouse Brain And Its Impact on Vocal Communication

Background Men are more susceptible to neurodevelopmental diseases such as autism and language deficits than women however, the underlying factors remain unclear. FOXP1 is associated with autism, intellectual disability and speech and language deficits, while FOXP2 is exclusively involved in speech and language disorder. FOXP1 and FOXP2 together form heterodimers for transcriptional regulation. Methods Generation of mouse models, Quantitative real-time PCR, Protein, antibodies and western blotting, Pup ultrasonic vocalization recordings, Immunofluorescence. Results In this study, we analyzed Foxp1 and Foxp2 expression in the developing mouse brain and observed sex-biased expression of Foxp1 and Foxp2 in the striatum at embryonic day (E) 17.5 and postnatal day (P) 7.5. Since the striatum is implicated in social and vocal communication, we investigated isolation-induced ultrasonic vocalization in brain-specific Foxp1NesCre mice. Foxp1NesCre pups had strongly reduced ultrasonic vocalization and lacked the sex-specific call rate from wild type pups, indicating that Foxp1 is important for normal ultrasonic vocalization. In addition, Foxp1 expression was reduced in the striatum of brain-specific androgen receptor KO mice at E17.5 and P7.5, suggesting that androgens significantly contribute to the sex-specific differences in Foxp1 expression and sex-dimorphic ultrasonic vocalization. Discussion Our findings demonstrate a spatio-temporal pattern of Foxp1 and Foxp2 expression at distinct stages in the developing mouse brain, directly or indirectly regulated by androgens. This regulation seems to mediate sex-specific differences in USV, commonly used as a readout for social behavior. The present study contributes to the understanding how testosterone may influence gene expression during human brain development, and helps to assess its impact on the etiology of social and communicative behavior in autism spectrum disorder.

Contrast Enhancement without Transient Map Expansion for Species-Specific Vocalizations in Core Auditory Cortex during Learning

Tonotopic map plasticity in the adult auditory cortex (AC) is a well established and oft-cited measure of auditory associative learning in classical conditioning paradigms. However, its necessity as an enduring memory trace has been debated, especially given a recent finding that the areal expansion of core AC tuned to a newly relevant frequency range may arise only transiently to support auditory learning. This has been reinforced by an ethological paradigm showing that map expansion is not observed for ultrasonic vocalizations (USVs) or for ultrasound frequencies in postweaning dams for whom USVs emitted by pups acquire behavioral relevance. However, whether transient expansion occurs during maternal experience is not known, and could help to reveal the generality of cortical map expansion as a correlate for auditory learning. We thus mapped the auditory cortices of maternal mice at postnatal time points surrounding the peak in pup USV emission, but found no evidence of frequency map expansion for the behaviorally relevant high ultrasound range in AC. Instead, regions tuned to low frequencies outside of the ultrasound range show progressively greater suppression of activity in response to the playback of ultrasounds or pup USVs for maternally experienced animals assessed at their pups' postnatal day 9 (P9) to P10, or postweaning. This provides new evidence for a lateral-band suppression mechanism elicited by behaviorally meaningful USVs, likely enhancing their population-level signal-to-noise ratio. These results demonstrate that tonotopic map enlargement has limits as a construct for conceptualizing how experience leaves neural memory traces within sensory cortex in the context of ethological auditory learning.

Analysis of within Subjects Variability in Mouse Ultrasonic Vocalization: Pups Exhibit Inconsistent, State-Like Patterns of Call Production.

Mice produce ultrasonic vocalizations (USV) in multiple communicative contexts, including adult social interaction (e.g., male to female courtship), as well as pup calls when separated from the dam. Assessment of pup USV has been widely applied in models of social and communicative disorders, dozens of which have shown alterations to this conserved behavior. However, features such as call production rate can vary substantially even within experimental groups and it is unclear to what extent aspects of USV represent stable trait-like influences or are vulnerable to an animal's state. To address this question, we have employed a mixed modeling approach to describe consistency in USV features across time, leveraging multiple large cohorts recorded from two strains, and across ages/times. We find that most features of pup USV show consistent patterns within a recording session, but inconsistent patterns across postnatal development. This supports the conclusion that pup USV is most strongly influenced by “state”-like variables. In contrast, adult USV call rate and call duration show higher consistency across sessions and may reflect a stable “trait.” However, spectral features of adult song such as the presence of pitch jumps do not show this level of consistency, suggesting that pitch modulation is more susceptible to factors affecting the animal's state at the time of recording. Overall, the utility of this work is three-fold. First, as variability necessarily affects the sensitivity of the assay to detect experimental perturbation, we hope the information provided here will be used to help researchers plan sufficiently powered experiments, as well as prioritize specific ages to study USV behavior and to decide which features to consider most strongly in analysis. Second, via the mouseTube platform, we have provided these hundreds of recordings and associated data to serve as a shared resource for other researchers interested in either benchmark data for these strains or in developing algorithms for studying features of mouse song. Finally, we hope that this work informs both interpretation of USV studies in models of developmental disorder, and helps to further research into understanding the neural processes that contribute to the production and predictability of USV behavior.

Mutual mother-infant recognition in mice: The role of pup ultrasonic vocalizations

The importance of the mother-infant bond for the development of offspring health and sociality has been studied not only in primate species but also in rodent species. A social bond is defined as affiliative behaviors toward a specific partner. However, controversy remains concerning whether mouse pups can distinguish between their own mother and an alien mother, and whether mothers can differentiate their own pups from alien pups. In this study, we investigated whether mutual recognition exists between mother and infant in ICR mice. Furthermore, we studied pup ultrasonic vocalizations (USVs), which are emitted by pups when isolated from their mothers, to determine whether they constituted an individual signature used by the mother for pup recognition. We conducted a variety of two-choice tests and selective-retrieving tests. In a two-choice test for mother recognition by the pup, pups between the ages of 17 and 21days preferred their own mothers to alien mothers. In a two-choice test for pup recognition by its mother, the mothers located their own pups faster than alien pups at the beginning of the test, yet displayed similar retrieving activity for both their own and alien pups in the subsequent selective-retrieving test. Furthermore, after recording USVs from pups from subject and alien mothers, then playing them simultaneously, subject mothers displayed a preference for pup USVs emitted by their own pups. Overall, our findings support the existence of mother-infant bonding in mice and suggest that pup USVs contribute to pup recognition by mothers.

Maternal Deprivation Influences Pup Ultrasonic Vocalizations of C57BL/6J Mice.

Maternal deprivation (MD) is frequently used as an early life stress model in rodents to investigate behavioral and neurological responses under stressful conditions. However, the effect of MD on the early postnatal development of rodents, which is when multiple neural systems become established, is rarely investigated due to methodological limitations. Ultrasonic vocalizations (USVs) are one of the few responses produced by neonatal rodents that can be quantitatively analyzed, and the quantification of USVs is regarded as a novel approach to investigate possible alterations in the neurobehavioral and emotional development of infant rodents under stress. To investigate the effect of MD on pup mice, we subjected C57BL/6J mice to MD and recorded the USVs of pups on postnatal days 1, 3, 7, 8, and 14. To determine whether the effect of MD on USVs was acute or cumulative, pre- and post-separation USV groups were included; sex differences in pup USV emission were also investigated. Our results suggest that (i) USV activity was high on postnatal days 3–8; (ii) the MD effect on USVs was acute, and a cumulative effect was not found; (iii) the MD mice vocalized more and longer than the controls at a lower frequency, and the effect was closely related to age; and (iv) female pups were more susceptible than males to the effect of MD on USV number and duration between postnatal days 3–8.

Recording Mouse Ultrasonic Vocalizations to Evaluate Social Communication

Mice emit ultrasonic vocalizations in different contexts throughout development and in adulthood. These vocal signals are now currently used as proxies for modeling the genetic bases of vocal communication deficits. Characterizing the vocal behavior of mouse models carrying mutations in genes associated with neuropsychiatric disorders such as autism spectrum disorders will help to understand the mechanisms leading to social communication deficits. We provide here protocols to reliably elicit ultrasonic vocalizations in pups and in adult mice. This standardization will help reduce inter-study variability due to the experimental settings. Pup isolation calls are recorded throughout development from individual pups isolated from dam and littermates. In adulthood, vocalizations are recorded during same-sex interactions (without a sexual component) by exposing socially motivated males or females to an unknown same-sex conspecific. We also provide a protocol to record vocalizations from adult males exposed to an estrus female. In this context, there is a sexual component in the interaction. These protocols are established to elicit a large amount of ultrasonic vocalizations in laboratory mice. However, we point out the important inter-individual variability in the vocal behavior of mice, which should be taken into account by recording a minimal number of individuals (at least 12 in each condition). These recordings of ultrasonic vocalizations are used to evaluate the call rate, the vocal repertoire and the acoustic structure of the calls. Data are combined with the analysis of synchronous video recordings to provide a more complete view on social communication in mice. These protocols are used to characterize the vocal communication deficits in mice lacking ProSAP1/Shank2, a gene associated with autism spectrum disorders. More ultrasonic vocalizations recordings can also be found on the mouseTube database, developed to favor the exchange of such data.

Recording Mouse Ultrasonic Vocalizations to Evaluate Social Communication.

Mice emit ultrasonic vocalizations in different contexts throughout development and in adulthood. These vocal signals are now currently used as proxies for modeling the genetic bases of vocal communication deficits. Characterizing the vocal behavior of mouse models carrying mutations in genes associated with neuropsychiatric disorders such as autism spectrum disorders will help to understand the mechanisms leading to social communication deficits. We provide here protocols to reliably elicit ultrasonic vocalizations in pups and in adult mice. This standardization will help reduce inter-study variability due to the experimental settings. Pup isolation calls are recorded throughout development from individual pups isolated from dam and littermates. In adulthood, vocalizations are recorded during same-sex interactions (without a sexual component) by exposing socially motivated males or females to an unknown same-sex conspecific. We also provide a protocol to record vocalizations from adult males exposed to an estrus female. In this context, there is a sexual component in the interaction. These protocols are established to elicit a large amount of ultrasonic vocalizations in laboratory mice. However, we point out the important inter-individual variability in the vocal behavior of mice, which should be taken into account by recording a minimal number of individuals (at least 12 in each condition). These recordings of ultrasonic vocalizations are used to evaluate the call rate, the vocal repertoire and the acoustic structure of the calls. Data are combined with the analysis of synchronous video recordings to provide a more complete view on social communication in mice. These protocols are used to characterize the vocal communication deficits in mice lacking ProSAP1/Shank2, a gene associated with autism spectrum disorders. More ultrasonic vocalizations recordings can also be found on the mouseTube database, developed to favor the exchange of such data.

A Mutation Associated with Stuttering Alters Mouse Pup Ultrasonic Vocalizations

A promising approach to understanding the mechanistic basis of speech is to study disorders that affect speech without compromising other cognitive or motor functions. Stuttering, also known as stammering, has been linked to mutations in the lysosomal enzyme-targeting pathway, but how this remarkably specific speech deficit arises from mutations in a family of general "cellular housekeeping" genes is unknown. To address this question, we asked whether a missense mutation associated with human stuttering causes vocal or other abnormalities in mice. We compared vocalizations from mice engineered to carry a mutation in the Gnptab (N-acetylglucosamine-1-phosphotransferase subunits alpha/beta) gene with wild-type littermates. We found significant differences in the vocalizations of pups with the human Gnptab stuttering mutation compared to littermate controls. Specifically, we found that mice with the mutation emitted fewer vocalizations per unit time and had longer pauses between vocalizations and that the entropy of the temporal sequence wassignificantly reduced. Furthermore, Gnptab missense mice were similar to wild-type mice on an extensive battery of non-vocal behaviors. We then used the same language-agnostic metrics for auditory signal analysis of human speech. We analyzed speech from people who stutter with mutations in this pathway and compared it to control speech and found abnormalities similar to those found in the mouse vocalizations. These data show that mutations in the lysosomal enzyme-targeting pathway produce highly specific effects in mouse pup vocalizations and establish the mouse as an attractive model for studying this disorder.

Vocal coselection in rat pup ultrasonic vocalizations.

Selective breeding and natural selection that select for one trait often bring along other correlated traits via coselection. Selective breeding for an infantile trait, high or low call rates of isolation‐induced ultrasonic vocalization of rat pups, also alters functions of some brain systems and emotional behaviors throughout life. We examined the effect of breeding for call rate on acoustic parameters that are of communicative significance. Selecting for higher call rate produced calls of significantly increased amplitude and bandwidth relative to a randomly bred line. Selecting for lower rate produced calls of decreased duration. These nonmorphological, functional trait changes demonstrate enhanced communicatory potential and energy expenditure for the High line and the opposite for the Low line. This demonstration of coselection in a communicatory system suggests an underlying heritable suite of linked acoustic vocalization characteristics that in noisy environments could enhance dam–pup communication and lead to selection of emotionality traits with beneficial responses to stress.