High‐throughput analysis of vocalizations reveals sex‐specific changes in Fmr1 mutant pups

• Published in: Genes, brain and behavior Vol. 19; no. 2; pp. e12611 - n/a
• Main Authors: Nolan, Suzanne O., Hodges, Samantha L., Lugo, Joaquin N.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2020; John Wiley & Sons, Inc
• Subjects: Animal models; autism; Calling behavior; Classification; FMR1 protein; Fragile X syndrome; gender; Heterozygotes; Intellectual disabilities; MATLAB; Mutants; Neonates; Rodents; Sex; Sex differences; Taxonomy; ultrasonic vocalizations; Vocalization behavior; Fragile X syndrome; gender; ultrasonic vocalizations; MATLAB; autism
• DOI: 10.1111/gbb.12611
• ISSN: 1601-1848

There have been several reports that individuals with Fragile X syndrome (FXS) and animal models of FXS have communication deficits. The present study utilized two different call classification taxonomies to examine the sex‐specificity of ultrasonic vocalization (USV) production on postnatal day (PD8) in the FVB strain of Fmr1 knockout (KO) mice. One classification protocol requires the investigator to score each call by hand, while the other protocol uses an automated algorithm. Results using the hand‐scoring protocol indicated that male Fmr1 KO mice exhibited longer calls (P = .03) than wild types on PD8. Male KOs also produced fewer complex, composite, downward, short and two‐syllable call‐types, as well as more frequency steps and chevron call‐types. Female heterozygotes exhibited no significant changes in acoustic or temporal aspects of calls, yet showed significant changes in call‐type production proportions across two different classification taxonomies (P < .001). They exhibited increased production of harmonic and frequency steps calls, as well as fewer chevron, downward and short calls. According to the second high‐throughput analysis, female heterozygotes produced significantly fewer single‐type and more multiple‐type syllables, unlike male KOs that showed no changes in these aspects of syllable production. Finally, we correlated both scoring methods and found a high level of correlation between the two methods. These results contribute further knowledge of sex differences in USV calling behavior for Fmr1 heterozygote and KO mice and provide a foundation for the use of high‐throughput analysis of neonatal USVs. Male Fmr1 KOs demonstrate quantitative changes in vocalizations on day 8, while female Fmr1 HETs show only qualitative changes.