Acoustic alterations of ultrasonic vocalization in the autism model mice (duplication of 15 q11-13) upon maternal isolation

Objective Autism spectrum disorder (ASD) has been increasing and one of serious problems worldwide. Gene mutations are main factors to cause ASD and various model mice are developing based on gene mutations. We used the B6.129S7-Dp (7Herc2-Mkrn3)1Taku mouse model and examined whether these model pups display alterations of ultrasonic vocalizations (USVs) to call the dam, suggesting pup–dam communication disorder.

Methods The pups were individually isolated from their dam and littermates and repeatedly recorded USVs for 5 min on PNDs 4, 7, 10, 13, 16, and 19. Acoustic characteristics of USVs were compared with those produced by wild-type pups (C57BL6/J).

Results The model pups (MP) displayed remarkable increases of USVs on PNDs 10 and 13 compared with the wild-type pups (WP). MP exhibited increases of USVs with longer durations (15–100ms), frequency-modulation (more than 2 kHz), and 2 syllables on PNDs 7–13. In contrast, WP displayed increases of USVs with shorter durations (4–15ms), flat frequency (less than 2 kHz), and 1 syllable on PNDs 7–13. USVs were classified into 14 categories based on syllable, duration, and frequency-modulation. MP produced more USVs categorized into Down and Step up types, whereas WP produced more USVs categorized into Short type.

Conclusion Maternal isolation induces higher anxiety in pups because pups are unable to survive without maternal care. Reductions of brain serotonin levels were reported in MP, suggesting latent anxiety disorder. We conclude that MP produced USVs described above due to hyper-anxiety rather than communication disorder.
Keywords: ASD, mouse model, maternal isolation, ultrasonic vocalization