Tauopathy in the periaqueductal gray, kölliker-fuse nucleus and nucleus retroambiguus is not predicted by ultrasonic vocalization in tau-P301L mice

Abstract

Upper airway and vocalization control areas such as the periaqueductal gray (PAG), kölliker-fuse nucleus (KF) and nucleus retroambiguus (NRA) are prone to developing tauopathy in mice expressing the mutant human tau P301L protein. Consequently, impaired ultrasonic vocalization (USV) previously identified in tau-P301L mice at the terminal disease stage of 8–9 months of age, was attributed to the presence of tauopathy in these regions. Our aim was to establish whether the onset of USV disorders manifest prior to the terminal stage, and if USV disorders are predictive of the presence of tauopathy in the PAG, KF and NRA. USVs produced by tau-P301L and wildtype mice aged 3–4, 5–6 or 8–9 months were recorded during male-female interaction. Immunohistochemistry was then performed to assess the presence or degree of tauopathy in the PAG, KF and NRA of mice displaying normal or abnormal USV patterns. Comparing various USV measurements, including the number, duration and frequency of calls, revealed no differences between tau-P301L and wildtype mice across all age groups, and linear discriminant analysis also failed to identify separate USV populations. Finally, the presence of tauopathy in the PAG, KF and NRA in individual tau-P301L mice did not reliably associate with USV disorders. Our findings that tauopathy in designated mammalian vocalization centres, such as the PAG, KF and NRA, did not associate with USV disturbances in tau-P301L mice questions whether USV phenotypes in this transgenic mouse are valid for studying tauopathy-related human voice and speech disorders.