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NS-Pten adult knockout mice display both quantitative and qualitative changes in urine-induced ultrasonic vocalizations.

ABSTRACT: The NS-Pten knockout (KO) mouse exhibits hyperactivity of the mammalian target of rapamycin (mTOR) and is a model of autism spectrum disorder (ASD). ASD presents with marked deficits in communication which can be elucidated by investigating their counterpart in mice, ultrasonic vocalizations (USVs). While USVs have been found to be altered in NS-Pten KO pups, no study has assessed whether this communication deficit persists into adulthood. In the present study, we investigate female urine-induced USVs, scent marking behavior, and open field activity in NS-Pten KO and wildtype (WT) adult male mice. Results showed that there was no difference in the quantity of vocalizations produced between groups, however, there were extensive alterations in the spectral properties of USVs. KO mice emitted vocalizations of a lower peak frequency, shorter duration, and higher peak amplitude compared to WT mice. KO animals also emitted a significantly different distribution of call-types relative to controls, displaying increased complex and short calls, but fewer upward, chevron, frequency steps, and composite calls. No significant differences between groups were observed for scent marking behavior and there was no difference between groups in the amount of time spent near the female urine. Overall, this study demonstrated that mTOR hyperactivity contributes to communication deficits in adult mice.

SUBMITTER: Binder MS

PROVIDER: S-EPMC7000110 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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NS-Pten adult knockout mice display both quantitative and qualitative changes in urine-induced ultrasonic vocalizations.

Binder Matthew S MS Jones Dalton G DG Hodges Samantha L SL Lugo Joaquin N JN

Behavioural brain research 20191003

The NS-Pten knockout (KO) mouse exhibits hyperactivity of the mammalian target of rapamycin (mTOR) and is a model of autism spectrum disorder (ASD). ASD presents with marked deficits in communication which can be elucidated by investigating their counterpart in mice, ultrasonic vocalizations (USVs). While USVs have been found to be altered in NS-Pten KO pups, no study has assessed whether this communication deficit persists into adulthood. In the present study, we investigate female urine-induce ...[more]

PMID: 31586563

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Project description:Objective:The goal of this study was to identify changes in quantitative and qualitative aspects of neonatal ultrasonic vocalizations USVs in neuron-subset specific (NS-Pten) knockout males and females when compared with wild-type male and female mice. Background:One signaling cascade that plays a crucial role in the development of an autistic-like phenotype is the PI3K/Akt/mTOR pathway. Mouse models that illustrate this connection include Fmr1, Tsc1, and NS-Pten-deficient mice. While numerous studies have investigated ultrasonic vocalizations in Fmr1 knockout and Tsc1 heterogenous mice, none have investigated USVs in NS-Pten knockout mice using a full spectrum recording system. Methods:We recorded ultrasonic vocalizations from NS-Pten wild-type and knockout male and female mice on postnatal days 8 and 11. On these days, we measured the number and quality of calls emitted from pups when they were removed from their mothers. Results:We found that knockout pups emitted fewer vocalizations for both sexes (p < .05). Knockout males had calls of a shorter duration and lower peak amplitude on day 8, while showing a shorter duration, lower peak amplitude, and higher peak and fundamental frequency on day 11 (p < .001). Knockout females vocalized at a lower peak amplitude and fundamental frequency, and a higher peak frequency on day 8, while showing a shorter duration and a higher peak and fundamental frequency on day 11 (p < .001). Spectrographic analyses also revealed significant differences in call type for both genotypes and sexes (p < .05). Conclusions:These findings demonstrate that deletion of NS-Pten results in significant decreases in vocalizations across both sexes. Additionally, our findings indicate that the aberrant vocalizations and increased call duration seen in other mTOR models are also present in NS-Pten knockout mice. Our study provides evidence of a connection between hyperactive mTOR signaling and neonatal ultrasonic vocalizations.

Dataset Information

NS-Pten adult knockout mice display both quantitative and qualitative changes in urine-induced ultrasonic vocalizations.

Publications

NS-Pten adult knockout mice display both quantitative and qualitative changes in urine-induced ultrasonic vocalizations.

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