Rodents (especially Mus musculus and Rattus norvegicus) have been the most widely used models in biomedical research for many years. A notable shift has taken place over the last two decades, with mice taking a more and more prominent role in biomedical science compared to rats. This shift was primarily instigated by the availability of a much larger genetic toolbox for mice, particularly embryonic-stem-cell-based targeting technology for gene disruption. With the recent emergence of tools for altering the rat genome, notably genome-editing technologies, the technological gap between the two organisms is closing, and it is becoming more important to consider the physiological, anatomical, biochemical and pharmacological differences between rats and mice when choosing the right model system for a specific biological question. The aim of this short review and accompanying poster is to highlight some of the most important differences, and to discuss their impact on studies of human diseases, with a special focus on neuropsychiatric disorders.

It is well accepted that events that interfere with the normal program of neuronal differentiation and brain maturation may be relevant for the etiology of psychiatric disorders, setting the stage for synaptic disorganization that becomes functional later in life. In order to investigate molecular determinants for these events, we examined the modulation of the neurotrophin brain-derived neurotrophic factor (BDNF) and the glutamate NMDA receptor following 24 h maternal separation (MD) on postnatal day 9. We found that in adulthood the expression of BDNF as well as of NR-2A and NR-2B, two NMDA receptor forming subunits, were significantly reduced in the hippocampus of MD rats whereas, among other structures, a slight reduction of NR-2A and 2B was detected only in prefrontal cortex. These changes were not observed acutely, nor in pre-weaning animals. Furthermore we found that in MD rats the modulation of hippocampal BDNF in response to an acute stress was altered, indicating a persistent functional impairment in its regulation, which may subserve a specific role for coping with challenging situations. We propose that adverse events taking place during brain maturation can modulate the expression of molecular players of cellular plasticity within selected brain regions, thus contributing to permanent alterations in brain function, which might ultimately lead to an increased vulnerability for psychiatric diseases.

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