Analysis of morphological changes as a key method in studying psychiatric animal models

A major interest in the analysis of animal models of psychiatric diseases is their underlying cellular pathology and to gain information regarding whether pharmacological treatments, genetic differences or an altered environment exert an impact upon the brain morphology or on the morphology or activity of single neurones. In this review, several key methods will be introduced that allow the analysis of morphological changes that are frequently observed in psychiatric animal models. An overview of the techniques that enable dendritic arborisation, alterations in dendritic spines and changes in fibre densities to be analysed are described. Moreover, methods for the analysis of adult neurogenesis and neurodegeneration and for the analysis of neuronal activity in fixed brain tissue are described. An important step during the analysis of morphological changes is the estimation of the number of stained cells. Since conventional cell counting methods have several limitations, two different approaches that permit an estimate of the number of stained cells within three-dimensional tissue are also discussed.