Comprehensive characterization of motor and coordination functions in three adolescent wild-type mouse strains

Ahmed Eltokhi,Barbara Kurpiers,Claudia Pitzer

doi:10.1038/s41598-021-85858-3

Abstract

Neuropsychiatric disorders are often associated with motor and coordination abnormalities that have important implications on the etiology, pathophysiology, and management of these disorders. Although the onset of many neuropsychiatric disorders including autism spectrum disorder, schizophrenia, and attention-deficit hyperactivity disorder emerges mainly during infancy and adolescence, most of the behavioral studies in mice modeling neuropsychiatric phenotypes are performed in adult animals, possibly missing valuable phenotypic information related to the effect of synaptic maturation during development. Here, we examined which behavioral tests assessing both motor and coordination functions can be performed in mice at two different adolescent stages. As strain and sex affect mouse behavior, our experiments covered both male and female mice of three inbred wild-type strains, C57BL/6N, DBA/2, and FVB/N. Adolescent mice of both postnatal days (P)22–30 and P32–40 developmental stages were capable of mastering common motor and coordination tests. However, results differed significantly between strains and sexes. Moreover, the 10-day interval between the two tested cohorts uncovered a strong difference in the behavioral results, confirming the significant impact of maturation on behavioral patterns. Interestingly, the results of distinct behavioral experiments were directly correlated with the weight of mice, which may explain the lack of reproducibility of some behavioral results in genetically-modified mice. Our study paves the way for better reproducibility of behavioral tests by addressing the effect of the developmental stage, strain, sex, and weight of mice on achieving the face validity of neuropsychiatric disorder-associated motor dysfunctions.

Highlights

Neuropsychiatric disorders are often associated with motor and coordination abnormalities that have important implications on the etiology, pathophysiology, and management of these disorders
Coordination and motor dysfunctions have been well documented in autism spectrum disorder (ASD)2–6, schizophrenia[7,8,9,10,11], attention-deficit hyperactivity disorder (ADHD)[12,13,14], and depression[15,16,17] and have important implications for the etiology18,19, pathophysiology[20], and management[21,22] of these disorders
As we have previously shown that behavioral results including ultrasonic vocalizations (USV)[42] and home-cage a ctivity[43] are sensitive to a small developmental progress during adolescence, we performed our behavioral test battery on two cohorts of mice, one from P22 to P30 and the other from P32 to P40 in order to draw a full picture of the motor ability during adolescence

Summary

Introduction

Neuropsychiatric disorders are often associated with motor and coordination abnormalities that have important implications on the etiology, pathophysiology, and management of these disorders. As strain and sex affect mouse behavior, our experiments covered both male and female mice of three inbred wild-type strains, C57BL/6N, DBA/2, and FVB/N Adolescent mice of both postnatal days (P)[22,23,24,25,26,27,28,29,30] and P32–40 developmental stages were capable of mastering common motor and coordination tests. Coordination and motor dysfunctions have been well documented in autism spectrum disorder (ASD)2–6, schizophrenia[7,8,9,10,11], attention-deficit hyperactivity disorder (ADHD)[12,13,14], and depression[15,16,17] and have important implications for the etiology18,19, pathophysiology[20], and management[21,22] of these disorders They are considered established markers of illness episodes and severity[19]. Because the genetic background and sexes are known to influence behavioral characteristics[42,43,44,45], we performed our experiments on male and female mice of three different inbred strains, C57BL/6N, DBA/2, and FVB/N that are world-wide used in research and are the standard strains in neuroscience with their ability to discern the role of individual genes and the impact of allelic variation along with decreased v ariability[46,47,48,49]

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