Combinatorial Behavioural Phenotyping of Mouse Models of Schizophrenia

Abstract

Schizophrenia is a severe and incurable mental disorder with a complex multigenetic nature that interacts with pathogenic environmental factors. The biggest challenge is to understand the molecular–cellular and behavioural changes that precede the onset of schizophrenia, which could open possibilities for preventive therapies to “re-wire” the neuronal plasticity of the brain and overcome the full expression of this mental disorder. Mouse behavioural phenotyping is an essential part of this research. However, there is a need to optimize the design of longitudinal behavioural experiments to compare findings across independent research groups and generate generalizable conclusions with translational values. Here we discuss the main principles of how to design behavioural experiments to study “pre-schizophrenia”-relevant phenotypes in mice, including the order of tests across the lifespan, application of new analytic tools, and parametric manipulations to adjust the sensitivity of tests for adolescent animals. We highlight the integration of image recognition tools into the behavioural pipeline which shows a high sensitivity for the detection of behaviour in young mice. Accumulated information acquired during early postnatal and adolescent periods in mice will help to determine biomarkers related to schizophrenia in genetic mouse lines. Altogether, longitudinal phenotyping of mice for schizophrenia should integrate cognitive assessments with sensory, metabolic, and circadian tests coupled with modern analytic tools. Systematic collection of phenotyping data will allow the generation of a schizophrenia animal model database to facilitate our understanding of mouse behaviour and the underlying molecular and cellular changes during critical periods of neurodevelopment.