Rigor and reproducibility in rodent behavioral research

Abstract

Behavioral neuroscience research incorporates the identical high level of meticulous methodologies and exacting attention to detail as all other scientific disciplines. To achieve maximal rigor and reproducibility of findings, well-trained investigators employ a variety of established best practices. Here we explicate some of the requirements for rigorous experimental design and accurate data analysis in conducting mouse and rat behavioral tests. Novel object recognition is used as an example of a cognitive assay which has been conducted successfully with a range of methods, all based on common principles of appropriate procedures, controls, and statistics. Directors of Rodent Core facilities within Intellectual and Developmental Disabilities Research Centers contribute key aspects of their own novel object recognition protocols, offering insights into essential similarities and less-critical differences. Literature cited in this review article will lead the interested reader to source papers that provide step-by-step protocols which illustrate optimized methods for many standard rodent behavioral assays. Adhering to best practices in behavioral neuroscience will enhance the value of animal models for the multiple goals of understanding biological mechanisms, evaluating consequences of genetic mutations, and discovering efficacious therapeutics.

Chronic PD-1 Checkpoint Blockade Does Not Affect Cognition or Promote Tau Clearance in a Tauopathy Mouse Model

“…In this study, we were not able to compare our JNPL3 mice to non-transgenic mice of the same strain background but based on prior historical data from the Sigurdsson lab and the literature, the JNPL3 mice appear to be impaired in novel object recognition and in the fear conditioning task. In the former test, wild-type mice, younger JNPL3 tauopathy mice, and tauopathy mice in which treatment has been effective, typically spend about 70% of their time with the novel object (Asuni et al, 2007;Boutajangout et al, 2010;Gulinello et al, 2019). In the current study, object preference in both IgG-and PD-1-treated JNPL3 mice did not significantly differ from chance performance (50%).…”

Experiments done in Black-6 mice: what does it mean?

“…In general, the phenotypic differences between the inbred strains have been shown to be stable and robust 88 . However, for obtaining such replicability (external validity), certain quality of study design and conduct (internal validity) is needed 89,90 . The phenotypic differences between the genetically close sub-strains of the C57BL/6 mice, coupled with the effect of vendor highlight the possible problems associated with choosing the background for genetically modified mice, interpretation of the results and reproducibility of the findings.…”

Systematic review of guidelines for internal validity in the design, conduct and analysis of preclinical biomedical experiments involving laboratory animalsSystematic review of guidelines for internal validity in the design, conduct and analysis of preclinical biomedical experiments involving laboratory animals

“…Of these, 62 publications were retained after full-text screening. We later identified two further duplicate publications of the same guidelines in different journals, giving a final list of 60 publications 5 7–65…”