2-Chloro-3,7,8-tribromodibenzofuran as a new environmental pollutant inducing atypical ultrasonic vocalization in infant mice
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PROVIDER: S-EPMC10615804 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Project description:Studies in rodent models suggest that calls emitted by isolated pups serve as an early behavioral manifestation of communication deficits and autistic like behavior. Previous studies in our labs showed that gestational exposure to the pesticide chlorpyrifos (CPF) and the Mthfr-knock-out mice are associated with impaired social preference and restricted or repetitive behavior. To extend these studies, we examine how pup communication via ultrasonic vocalizations is altered in these ASD models. We implemented an unsupervised hierarchical clustering method based on the spectral properties of the syllables in order to exploit syllable classification to homogeneous categories while avoiding over-categorization. Comparative exploration of the spectral and temporal aspects of syllables emitted by pups in two ASD models point to the following: (1) Most clusters showed a significant effect of the ASD factor on the start and end frequencies and bandwidth and (2) The highest percent change due to the ASD factor was on the bandwidth and duration. In addition, we found sex differences in the spectral and temporal properties of the calls in both control groups as well as an interaction between sex and the gene/environment factor. Considering the basal differences in the characteristics of syllables emitted by pups of the C57Bl/6 and Balb/c strains used as a background in the two models, we suggest that the above spectral-temporal parameters start frequency, bandwidth, and duration are the most sensitive USV features that may represent developmental changes in ASD models.
| S-EPMC8645772 | biostudies-literature
Project description:Alpha-synuclein is an abundant protein implicated in synaptic function and plasticity, but the molecular mechanism of its action is not understood. Missense mutations and gene duplication/triplication events result in Parkinson's disease, a neurodegenerative disorder of old age with impaired movement and emotion control. Here, we systematically investigated the striatal as well as the cerebellar transcriptome profile of alpha-synuclein-deficient mice via a genome-wide microarray survey in order to gain hypothesis-free molecular insights into the physiological function of alpha-synuclein. A genotype-dependent, specific and strong downregulation of forkhead box P1 (Foxp1) transcript levels was observed in all brain regions from postnatal age until old age and could be validated by qPCR. In view of the co-localization and heterodimer formation of FOXP1 with FOXP2, a transcription factor with a well established role for vocalization, and the reported regulation of both alpha-synuclein and FOXP2 expression during avian song learning, we performed a detailed assessment of mouse movements and vocalizations in the postnatal period. While there was no difference in isolation-induced behavioral activity in these animals, the alpha-synuclein-deficient mice exhibited an increased production of isolation-induced ultrasonic vocalizations (USVs). This phenotype might also reflect the reduced expression of the anxiety-related GABA-A receptor subunit gamma 2 (Gabrg2) we observed. Taken together, we identified an early behavioral consequence of alpha-synuclein deficiency and accompanying molecular changes, which supports the notion that the neural connectivity of sound or emotion control systems is affected.
2010-07-22 | GSE19534 | GEO
Project description:Recurrent deletions and duplications at chromosomal region 16p11.2 are variably associated with speech delay, autism spectrum disorder, developmental delay, schizophrenia, and cognitive impairments. Social communication deficits are a primary diagnostic symptom of autism. Here we investigated ultrasonic vocalizations (USVs) in young adult male 16p11.2 deletion mice during a novel three-phase male-female social interaction test that detects vocalizations emitted by a male in the presence of an estrous female, how the male changes its calling when the female is suddenly absent, and the extent to which calls resume when the female returns. Strikingly fewer vocalizations were detected in two independent cohorts of 16p11.2 heterozygous deletion males (+/-) during the first exposure to an unfamiliar estrous female, as compared to wildtype littermates (+/+). When the female was removed, +/+ emitted calls, but at a much lower level, whereas +/- males called minimally. Sensory and motor abnormalities were detected in +/-, including higher nociceptive thresholds, a complete absence of acoustic startle responses, and hearing loss in all +/- as confirmed by lack of auditory brainstem responses to frequencies between 8 and 100 kHz. Stereotyped circling and backflipping appeared in a small percentage of individuals, as previously reported. However, these sensory and motor phenotypes could not directly explain the low vocalizations in 16p11.2 deletion mice, since (a) +/- males displayed normal abilities to emit vocalizations when the female was subsequently reintroduced, and (b) +/- vocalized less than +/+ to social odor cues delivered on an inanimate cotton swab. Our findings support the concept that mouse USVs in social settings represent a response to social cues, and that 16p11.2 deletion mice are deficient in their initial USVs responses to novel social cues.
| S-EPMC5321681 | biostudies-literature
Project description:Alpha-synuclein is an abundant protein implicated in synaptic function and plasticity, but the molecular mechanism of its action is not understood. Missense mutations and gene duplication/triplication events result in Parkinson's disease, a neurodegenerative disorder of old age with impaired movement and emotion control. Here, we systematically investigated the striatal as well as the cerebellar transcriptome profile of alpha-synuclein-deficient mice via a genome-wide microarray survey in order to gain hypothesis-free molecular insights into the physiological function of alpha-synuclein. A genotype-dependent, specific and strong downregulation of forkhead box P1 (Foxp1) transcript levels was observed in all brain regions from postnatal age until old age and could be validated by qPCR. In view of the co-localization and heterodimer formation of FOXP1 with FOXP2, a transcription factor with a well established role for vocalization, and the reported regulation of both alpha-synuclein and FOXP2 expression during avian song learning, we performed a detailed assessment of mouse movements and vocalizations in the postnatal period. While there was no difference in isolation-induced behavioral activity in these animals, the alpha-synuclein-deficient mice exhibited an increased production of isolation-induced ultrasonic vocalizations (USVs). This phenotype might also reflect the reduced expression of the anxiety-related GABA-A receptor subunit gamma 2 (Gabrg2) we observed. Taken together, we identified an early behavioral consequence of alpha-synuclein deficiency and accompanying molecular changes, which supports the notion that the neural connectivity of sound or emotion control systems is affected. Factorial design comparing SNCA knock-out mice with wild type littermates in two different tissues (striatum, cerebellum) at two different timepoints (6 and 21 month)
2010-07-21 | E-GEOD-19534 | biostudies-arrayexpress
Project description:Mouse ultrasonic vocalizations (USVs) are studied in many fields of science. However, various noise and varied USV patterns in observed signals make complete automatic analysis difficult. We improve several methods to reduce noise, detect USV calls and automatically cluster USV calls. After reduction of noise and detection of USV calls, we consider USV calls as functional data and characterize them as USV functions with B-spline basis functions. For discontinuous USV calls, breakpoints in the USV functions are defined using multiple knots in the construction of the B-spline basis functions, and a hierarchical method is used to cluster the USV functions by shape. We finally show the performance of the proposed methods with USV data recorded for laboratory mice.
| S-EPMC5942836 | biostudies-literature
Project description:Neonatal vocalization is structurally altered in mouse models of autism spectrum disorder (ASD). Our published data showed that pup vocalization, under conditions of maternal separation, contains sequences whose alterations in a genetic mouse model of ASD impair social communication between pups and mothers. We describe details of a method which reveals the statistical structure of call sequences that are functionally critical for optimal maternal care. Entropy analysis determines the degree of non-random call sequencing. A Markov model determines the actual call sequences used by pups. Sparse partial least squares discriminant analysis (sPLS-DA) identifies call sequences that differentiate groups and reveals the degrees of individual variability in call sequences between groups. These three sets of analyses can be used to identify the otherwise hidden call structure that is altered in mouse models of developmental neuropsychiatric disorders, including not only autism but also schizophrenia. © 2018 by John Wiley & Sons, Inc.
| S-EPMC6055925 | biostudies-literature
Project description:Numerous animal species emit vocalizations in response to various social stimuli. The neural basis of vocal communication has been investigated in monkeys, songbirds, rats, bats, and invertebrates resulting in deep insights into motor control, neural coding, and learning. Mice, which recently became very popular as a model system for mammalian neuroscience, also utilize ultrasonic vocalizations (USVs) during mating behavior. However, our knowledge is lacking of both the behavior and its underlying neural mechanism. We developed a novel method for head-restrained male mice (HRMM) to interact with non-restrained female mice (NRFM) and show that mice can emit USVs in this context. We first recorded USVs in a free arena with non-restrained male mice (NRMM) and NRFM. Of the NRMM, which vocalized in the free arena, the majority could be habituated to also vocalize while head-restrained but only when a female mouse was present in proximity. The USVs emitted by HRMM are similar to the USVs of NRMM in the presence of a female mouse in their spectral structure, inter-syllable interval distribution, and USV sequence length, and therefore are interpreted as social USVs. By analyzing the vocalizations of NRMM, we established criteria to predict which individuals are likely to vocalize while head fixed based on the USV rate and average syllable duration. To characterize the USVs emitted by HRMM, we analyzed the syllable composition of HRMM and NRMM and found that USVs emitted by HRMM have a higher proportion of USVs with complex spectral representation, supporting previous studies showing that mice social USVs are context dependent. Our results suggest a way to study the neural mechanisms of production and control of social vocalization in mice using advanced methods requiring head fixation.
| S-EPMC5165246 | biostudies-literature
Project description:Mice produce ultrasonic vocalizations (USVs) in a wide variety of social contexts, including courtship, investigation, and territorial defense. Despite the belief that mouse USVs are innate, social experience may be necessary for mice to learn the appropriate situation to emit USVs. Mouse USVs have been divided into categories based on their spectrotemporal parameters, but it is currently unclear if social experience changes these parameters (e.g., frequency and duration) or the proportion of calls from each category produced. Social isolation has been found to influence USV production in male mice. To investigate the influence of social isolation on vocal behavior in female mice, recordings were made of USVs emitted to unfamiliar male and female mice by subjects with one of three types of social experience. Twenty-four adult female CBA/CaJ mice either lived alone, lived with other females only, or lived with other females and had limited access to a male. Mice were recorded while in isolation, ensuring all recorded USVs were from the female of interest. Vocalizations were separated into nine categories and peak frequency, duration, and bandwidth were measured for every call. Socially isolated mice did not produce significantly more USVs or USV types than socially experienced mice. Social isolation did not have a significant effect on the features of USVs, suggesting production of USVs may not be learned in female mice.
| S-EPMC6400338 | biostudies-literature
Project description:Throughout life, rats emit ultrasonic vocalizations (USV) when confronted with an aversive situation. However, the conditions classically used to elicit USV vary greatly with the animal's age (isolation from the dam in infancy, versus nociceptive stimulation in adults). The present study is the first to characterize USV responses to the same aversive event throughout development. Specifically, infant, juvenile and adult rats were presented with mild foot-shocks and their USV frequency, duration, and relationship with respiration and behavior were compared. In juvenile and adult rats, a single class of USV is observed with an age-dependent main frequency and duration (30 kHz/400 ms in juveniles, 22 kHz/900 ms in adults). In contrast, infant rat USV were split into two classes with specific relationships with respiration and behavior: 40 kHz/300 ms and 66 kHz/21 ms. Next, we questioned if these infant USV were also emitted in a more naturalistic context by exposing pups to interactions with the mother treating them roughly. This treatment enhanced 40-kHz USV while leaving 66-kHz USV unchanged suggesting that the use of USV goes far beyond a signal studied in terms of amount of emission, and can inform us about some aspects of the infant's affective state.
| S-EPMC5647438 | biostudies-literature
Project description:Previous studies have demonstrated that mutation in the forkhead domain of the forkhead box P2 (FOXP2) protein (R553H) causes speech-language disorders. To further analyze FOXP2 function in speech learning, we generated a knockin (KI) mouse for Foxp2 (R552H) [Foxp2 (R552H)-KI], corresponding to the human FOXP2 (R553H) mutation, by homologous recombination. Homozygous Foxp2 (R552H)-KI mice showed reduced weight, immature development of the cerebellum with incompletely folded folia, Purkinje cells with poor dendritic arbors and less synaptophysin immunoreactivity, and achieved crisis stage for survival 3 weeks after birth. At postnatal day 10, these mice also showed severe ultrasonic vocalization (USV) and motor impairment, whereas the heterozygous Foxp2 (R552H)-KI mice exhibited modest impairments. Similar to the wild-type protein, Foxp2 (R552H) localized in the nuclei of the Purkinje cells and the thalamus, striatum, cortex, and hippocampus (CA1) neurons of the homozygous Foxp2 (R552H)-KI mice (postnatal day 10), and some of the neurons showed nuclear aggregates of Foxp2 (R552H). In addition to the immature development of the cerebellum, Foxp2 (R552H) nuclear aggregates may further compromise the function of the Purkinje cells and cerebral neurons of the homozygous mice, resulting in their death. In contrast, heterozygous Foxp2 (R552H)-KI mice, which showed modest impairment of USVs with different USV qualities and which did not exhibit nuclear aggregates, should provide insights into the common molecular mechanisms between the mouse USV and human speech learning and the relationship between the USV and motor neural systems.
| S-EPMC2268594 | biostudies-literature