Computational Analysis of Neonatal Mouse Ultrasonic Vocalization

Broin, Pilib Ó; Beckert, Michael; Takahashi, Tomohisa; Izumi, Tohru; Ye, Kenny; Kang, Gina; Pouso, Patricia; Topolski, Mackenzie A.; Peña, Jose L.; Hiroi, Noboru

doi:10.1002/cpmo.46

“…Because we find that the organization of a spatial auditory map in the SC is abnormal in these mice, we predict that even at two to four months of age, C57BL/6 mice may have sound recognition or localization defects. A number of important naturalistic sounds for mice are in the high-frequency range, such as pup calls and mating vocalizations ( Neunuebel et al, 2015 ; Ó Broin et al, 2018 ). This raises an interesting ethological question of whether and how C57BL/6 mice compensate for this high-frequency response deficit.…”

Section: Discussionmentioning

confidence: 99%

High-Frequency Hearing Is Required to Compute a Topographic Map of Auditory Space in the Mouse Superior Colliculus

Si

¹

,

Ito

²

,

Litke

³

et al. 2022

eNeuro

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A topographic map of auditory space is a feature found in the superior colliculus (SC) of many species, including CBA/CaJ mice. In this genetic background, high-frequency monaural spectral cues and interaural level differences (ILDs) are used to compute spatial receptive fields (RFs) that form a topographic map along the azimuth. Unfortunately, C57BL/6 mice, a strain widely used for transgenic manipulation, display age-related hearing loss (AHL) because of an inbred mutation in the Cadherin 23 gene ( Cdh23 ) that affects hair cell mechanotransduction. To overcome this problem, researchers have used young C57BL/6 mice in their studies, as they have been shown to have normal hearing thresholds. However, important details of the auditory response characteristics of the SC such as spectral responses and spatial localization, have not been characterized in young C57BL/6 mice. Here, we show that two- to four-month C57BL/6 mice lack neurons with frontal auditory RFs and therefore lack a topographic representation of auditory space in the SC. Analysis of the spectrotemporal RFs (STRFs) of the SC auditory neurons shows that C57BL/6 mouse SC neurons lack the ability to detect the high-frequency (>40 kHz) spectral cues that are needed to compute frontal RFs. We also show that crossing C57BL/6 mice with CBA/CaJ mice or introducing one copy of the wild-type Cdh23 to C57BL/6 mice rescues the high-frequency hearing deficit and improves the topographic map of auditory space. Taken together, these results demonstrate the importance of high-frequency hearing in computing a topographic map of auditory space.

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“…Because we find that the organization of a spatial auditory map in the SC is abnormal in these mice, we predict that even at 2-4 months of age, C57BL/6 mice may have sound recognition or localization defects. A number of important naturalistic sounds for mice are in the high-frequency range, such as pup calls and mating vocalizations (Neunuebel et al, 2015;Ó Broin et al, 2018). This raises an interesting ethological question of whether and how C57BL/6 mice compensate for this high-frequency response deficit.…”

Section: Discussionmentioning

confidence: 99%

High-frequency hearing is required for generating a topographic map of auditory space in the mouse superior colliculus

Si¹,

Ito

²

,

Litke³

et al. 2021

Preprint

0

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A topographic map of auditory space is a feature found in the superior colliculus (SC) of many species, including CBA/CaJ mice. In this genetic background, high-frequency monaural spectral cues and interaural level differences are used to generate spatial receptive fields (RFs) that form a topographic map along the azimuth. Unfortunately, C57BL/6 mice, a strain widely used for transgenic manipulation, display age-related hearing loss (AHL) due to an inbred mutation in the Cadherin 23 gene (Cdh23) that affects hair cell mechanotransduction. To overcome this problem, researchers have used young C57BL/6 mice in their studies, as they have been shown to have normal hearing thresholds. However, important details of the auditory response characteristics of the SC such as spectral responses and spatial localization, have not been characterized in young C57BL/6 mice.Here we show that 2-4-month C57BL/6 mice lack neurons with frontal auditory RFs and therefore lack a topographic representation of auditory space in the SC. Analysis of the spectrotemporal receptive fields (STRFs) of the SC auditory neurons shows that C57BL/6 mouse SC neurons lack the ability to detect the high-frequency (>40kHz) spectral cues that are needed to compute frontal RFs. We also show that crossing C57BL/6 mice with CBA/CaJ mice or introducing one copy of the wild-type Cdh23 to C57BL/6 mice rescues the high-frequency hearing deficit and improves the topographic map of auditory space. Taken together, these results demonstrate the importance of high-frequency hearing in computing a topographic map of auditory space.Significance StatementDespite the strain’s age-dependent hearing loss, C57BL/6 mice are widely used in auditory studies because of the development of transgenic reporter and Cre lines in this genetic background. Here we examined the topographic map of auditory space and spectrotemporal properties of neurons in the SC of C57BL/6 mice. We found an early-onset high-frequency hearing deficit that results in the loss of SC neurons with frontal RFs and, consequently, an absence of a topographic map of auditory space. These findings stress the importance of high-frequency hearing in generating spatially restricted receptive fields and serve as a caution to researchers that doing auditory-related research using the C57BL/6 genetic background may not be representative of true wild-type mice.

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“…We developed a coisogenic mouse model of 16p11.2 deletion (see Supplementary Information (SI) , Mouse and RNA-seq ). We recorded and analyzed their behaviors during the neonatal period (P8 and P12) [ 24 ], and during the postpubertal period starting at the age of 1 month (see SI , Behavioral Analyses ). The minimal sample size was determined by power analyses based on our previous study [ 16 ].…”

Section: Methodsmentioning

confidence: 99%

Computational identification of variables in neonatal vocalizations predictive for postpubertal social behaviors in a mouse model of 16p11.2 deletion

Nakamura

¹

,

Ye

²

,

Silva

³

et al. 2021

Self Cite

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Autism spectrum disorder (ASD) is often signaled by atypical cries during infancy. Copy number variants (CNVs) provide genetically identifiable cases of ASD, but how early atypical cries predict a later onset of ASD among CNV carriers is not understood in humans. Genetic mouse models of CNVs have provided a reliable tool to experimentally isolate the impact of CNVs and identify early predictors for later abnormalities in behaviors relevant to ASD. However, many technical issues have confounded the phenotypic characterization of such mouse models, including systematically biased genetic backgrounds and weak or absent behavioral phenotypes. To address these issues, we developed a coisogenic mouse model of human proximal 16p11.2 hemizygous deletion and applied computational approaches to identify hidden variables within neonatal vocalizations that have predictive power for postpubertal dimensions relevant to ASD. After variables of neonatal vocalizations were selected by least absolute shrinkage and selection operator (Lasso), random forest, and Markov model, regression models were constructed to predict postpubertal dimensions relevant to ASD. While the average scores of many standard behavioral assays designed to model dimensions did not differentiate a model of 16p11.2 hemizygous deletion and wild-type littermates, specific call types and call sequences of neonatal vocalizations predicted individual variability of postpubertal reciprocal social interaction and olfactory responses to a social cue in a genotype-specific manner. Deep-phenotyping and computational analyses identified hidden variables within neonatal social communication that are predictive of postpubertal behaviors.

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Computational Analysis of Neonatal Mouse Ultrasonic Vocalization

Cited by 7 publications

References 71 publications

High-Frequency Hearing Is Required to Compute a Topographic Map of Auditory Space in the Mouse Superior Colliculus

High-Frequency Hearing Is Required to Compute a Topographic Map of Auditory Space in the Mouse Superior Colliculus

High-frequency hearing is required for generating a topographic map of auditory space in the mouse superior colliculus

Computational identification of variables in neonatal vocalizations predictive for postpubertal social behaviors in a mouse model of 16p11.2 deletion

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