Dataset Information

Cadm1-expressing synapses on Purkinje cell dendrites are involved in mouse ultrasonic vocalization activity.

ABSTRACT: Foxp2(R552H) knock-in (KI) mouse pups with a mutation related to human speech-language disorders exhibit poor development of cerebellar Purkinje cells and impaired ultrasonic vocalization (USV), a communication tool for mother-offspring interactions. Thus, human speech and mouse USV appear to have a Foxp2-mediated common molecular basis in the cerebellum. Mutations in the gene encoding the synaptic adhesion molecule CADM1 (RA175/Necl2/SynCAM1/Cadm1) have been identified in people with autism spectrum disorder (ASD) who have impaired speech and language. In the present study, we show that both Cadm1-deficient knockout (KO) pups and Foxp2(R552H) KI pups exhibit impaired USV and smaller cerebellums. Cadm1 was preferentially localized to the apical-distal portion of the dendritic arbor of Purkinje cells in the molecular layer of wild-type pups, and VGluT1 level decreased in the cerebellum of Cadm1 KO mice. In addition, we detected reduced immunoreactivity of Cadm1 and VGluT1 on the poorly developed dendritic arbor of Purkinje cells in the Foxp2(R552H) KI pups. However, Cadm1 mRNA expression was not altered in the Foxp2(R552H) KI pups. These results suggest that although the Foxp2 transcription factor does not target Cadm1, Cadm1 at the synapses of Purkinje cells and parallel fibers is necessary for USV function. The loss of Cadm1-expressing synapses on the dendrites of Purkinje cells may be associated with the USV impairment that Cadm1 KO and Foxp2(R552H) KI mice exhibit.

SUBMITTER: Fujita E

PROVIDER: S-EPMC3260241 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Cadm1-expressing synapses on Purkinje cell dendrites are involved in mouse ultrasonic vocalization activity.

Fujita Eriko E Tanabe Yuko Y Imhof Beat A BA Momoi Mariko Y MY Momoi Takashi T

PloS one 20120117 1

Foxp2(R552H) knock-in (KI) mouse pups with a mutation related to human speech-language disorders exhibit poor development of cerebellar Purkinje cells and impaired ultrasonic vocalization (USV), a communication tool for mother-offspring interactions. Thus, human speech and mouse USV appear to have a Foxp2-mediated common molecular basis in the cerebellum. Mutations in the gene encoding the synaptic adhesion molecule CADM1 (RA175/Necl2/SynCAM1/Cadm1) have been identified in people with autism spe ...[more]

PMID: 22272290

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Project description: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.

Dataset Information

Cadm1-expressing synapses on Purkinje cell dendrites are involved in mouse ultrasonic vocalization activity.

Publications

Cadm1-expressing synapses on Purkinje cell dendrites are involved in mouse ultrasonic vocalization activity.

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