Spectral and temporal properties of calls reveal deficits in ultrasonic vocalizations of adult Fmr1 knockout mice

Abstract

The Fmr1 knockout (KO) mouse has commonly been used to investigate communication impairments, one of the key diagnostic symptoms observed in Fragile X syndrome (FXS) and Autism spectrum disorder (ASD). Many studies have found alterations in ultrasonic vocalizations (USVs) in neonatal Fmr1 KO mice, however, there is limited research investigating whether these deficits continue into adulthood. In the present study, we examine differences in female urine-induced ultrasonic vocalizations, scent marking behavior, odor discrimination, and open field activity in adult male Fmr1 KO and wildtype (WT) mice. Overall, we found extensive alterations between genotypes in both spectral and temporal properties of ultrasonic vocalizations. There was no difference in the average number of calls emitted by both genotypes, however, Fmr1 KO mice emitted calls of a higher frequency, decreased amplitude, and shorter duration than WT mice. Spectrographic analyses revealed statistically significant differences between genotypes in the types of calls emitted. Contrastingly, we found no differences in scent marking behavior, a form of social communication, or in odor discrimination and activity levels of the mice. The results corroborate previous studies emphasizing the importance of qualitative differences observed in vocalization behavior of Fmr1 KO mice, rather than quantitative measurements such as number of calls emitted. Overall, the study confirms the presence of abnormalities in vocalization behavior in adult Fmr1 KO mice that we believe are consistent with communication deficits seen in the syndrome.

Specific profile of ultrasonic communication in a mouse model of neurodevelopmental disorders

“…Furthermore, other call-typologies specific deficits are present in the literature, such as increased number of frequency jump calls on PND 7 50 , and decreased number of downward calls on PND 8 in Fmr1-KO compared to their WT pups 18 . Also at adulthood, during courtship Fmr1-KO mice emitted a higher proportion of upward syllables 19 , complex, chevron and flat , and a reduced number of composite and frequency steps than control mice 51 . In addition, as ultrasonic communication specific deficit, in another model of NDDs, Shank1 −/− mice, a categorical shift in the proportions of two clusters of frequency (first cluster between 50 and 80 kHz and second cluster between 80 and 100 kHz) was observed 22,52 .…”

Activity-dependent neuroprotective protein deficiency models synaptic and developmental phenotypes of autism-like syndrome

“…Adnp +/genotype exhibits significant decreases in ultrasonic vocalizations and developmental milestone delays, and daily NAP treatment partially reverses the phenotype. Ultrasonic vocalization (USV) calls of distress (40-70 kHz) were induced on P8 following separation from the dams (46,47). Results showed a 2-fold reduction in the number of all USVs in the Adnp +/mice, which was dramatically 117, P = 0.008] effects were found.…”

A neurophysiological model of speech production deficits in fragile X syndrome

“…Of note, several recent studies have documented that transcranial direct current stimulation over left IFG including Broca’s area reduced articulation errors and increased speech output in both individuals with autism spectrum disorder ( Schneider and Hopp, 2011 ) and individuals with chronic aphasia ( Fiori et al , 2011 ; Marangolo et al , 2011 , 2013 ; Mandelli et al , 2018 ). FMR1 KO mice demonstrate altered spectral and temporal properties of and reduced rate of ultrasonic vocalizations compared with wild type ( Roy et al , 2012 ; Hodges et al , 2017 ; Toledo et al , 2019 ), the latter which was rescued following drug treatment with minocycline in a recent study ( Toledo et al , 2019 ). The link between abnormal ultrasonic vocalizations and disrupted feedforward control/fronto-temporal connectivity remains to be determined; however, this suggests that pharmacological interventions also may useful in enhancing speech production in FXS.…”