Abnormal whisker movements in the 3xTg‐AD mouse model of Alzheimer's disease

Abstract

Alzheimer's disease is the most frequent form of dementia in elderly people. The triple transgenic (3xTg‐AD) mouse model of Alzheimer's Disease is important in biomedical research as these mice develop both neuropathological and behavioural phenotypes. However, their behavioural phenotype is variable, with findings depending on the specific task, as well as the age and sex of the mice. Whisker movements show motor, sensory and cognitive deficits in mouse models of neurodegenerative disease. Therefore, we examined whisker movements in 3, 12.5 and 17‐month‐old female 3xTg‐AD mice and their B6129S/F2 wildtype controls. Mice were filmed using a high‐speed video camera (500 fps) in an open arena during a novel object exploration task. Genotype and age differences were found in mice exploring the arena prior to object contact. Prior to whisker contact, the 3‐month‐old 3xTg‐AD mice had smaller whisker angles compared with the wildtype controls, suggesting an early motor phenotype in these mice. Pre‐contact mean angular position at 3 months and whisking amplitude at 17 months of age differed between the 3xTg‐AD and wildtype mice. During object contact 3xTg‐AD mice did not reduce whisker spread as frequently as the wildtype mice at 12.5 and 17 months, which may suggest sensory or attentional deficits. We show that whisker movements are a powerful behavioural measurement tool for capturing behavioural deficits in mouse models that show complex phenotypes, such as the 3xTg‐AD mouse model.

Maternal immune activation affects female offspring whisker movements during object exploration in a rat model of neurodevelopmental disorders

“…Measures of the PC whisker variables were analysed first. Changes in whisker movements during object exploration were analysed by subtracting the DC measures from the PC measures (PC-DC), as per Simanaviciute et al (2022) . Examining PC- metrics reveals common contact-related whisker behaviours ( Fig.…”

“…This is in contrast to counts and durations which are more common in behavioural testing, such as the tasks recommended for measuring attention by Lustig et al (2013) . Measuring rodent whisker movements has previously revealed motor, sensory and cognitive deficits in mouse models of neurodegenerative disease ( Grant ; Garland et al, 2018 ; Simanaviciute et al, 2020 , 2022 ), although it is probably not possible to disentangle these factors using the current set up. This method has also identified behavioural phenotypes earlier than any other behavioural test, e.g., in a R62 Huntington's Disease mouse model ( Garland et al, 2018 ).…”

“…We posit that measuring whisker movements could be such a robust test. Whiskers are an established sensorimotor model in neuroscience (see Adibi, 2019 for a recent review), and the precise measurement of whisker movements can be captured quickly without any animal training ( Simanaviciute et al, 2022 ), unlike in many other behavioural tasks. Furthermore, measurements are highly granular, including angles and speed.…”

“…This method has also identified behavioural phenotypes earlier than any other behavioural test, e.g., in a R62 Huntington's Disease mouse model ( Garland et al, 2018 ). Measuring whisker movements during object exploration can identify sensory and attentional deficits (5xFAD mice in Grant et al, 2018; 3xTg-AD mice in Simanaviciute et al, 2022 ), and reveal sex differences in mouse models of Alzheimer's (Grant et al, 2018) and Huntington's disease ( Simanaviciute et al, 2020 ), which makes it especially aligned for the study of NDDs. Indeed, Lins et al (2019) specifically recommend investigating sex differences in MIA research, since rat models of NDDs exhibit sex-dependent phenotypes ( Snigda et al, 2011 ; Leger and Neill, 2016 ; Nikolić et al, 2017 ; Casquero-Veiga et al, 2023 ; Potter et al, 2023 ).…”

“…Here, we applied our established mouse whisker measurement protocol ( Simanaviciute et al, 2020 , 2022 ) to the rat Poly I:C model to investigate the effects of in utero exposure to MIA on whisker movements in offspring at postnatal day (P) 50. We investigated whisker movements before and during object exploration, and examined differences between treatment, sex and object texture.…”