Multidimensional description of behavioural phenotypes: Role of serotonin in individual profiles of behaviour

• Applicants: Natalia Alenina, Ph.D.; Marion Rivalan, Ph.D.
• Subject Area: Biological Psychiatry
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 260217780

The complex nature of psychiatric disorders makes them some of the least understood and most incapacitating of all pathological conditions. Currently, the diagnosis of the majority of mental disorders lacks objective biological markers and specific combinations of behavioural symptoms. One approach to model psychiatric disorders is the search for neurocognitive endophenotypes (i.e. biologically heritable traits of mental disorders) in animal models. This can be achieved by identifying naturally vulnerable individuals through extensive behavioural diagnostics and by association of their specific behavioural profile to particular biological markers. The identification of such biological markers is necessary to refine the diagnosis of a mental illness and to eventually develop new therapeutic strategies. The serotonin system is a primary target in treating mood, impulsive control, and other aggression related mental disorders. The involvement of the serotonergic system in different mental illnesses supports the hypothesis of a common brain dysfunction underlying such mental pathology. Serotonin is a key neurotransmitter for regulating executive function and social behaviour, which are altered in many mental disorders. Intact social and cognitive abilities rely on the integrity of the serotonin connectivity in the prefrontal cortex (PFC). Low levels of serotonin signaling in the PFC compared to levels in subcortical brain areas (amygdala, ventral striatum) are known to have critical effects on aggression, decision making, impulsivity and attention. We will search for behavioural profiles related to mental disorders in which the serotonergic system plays a critical role in rats. This project is composed of two stages. First, we will establish detailed behavioural profiles for individuals of a normal population of rats to identify subgroups that naturally express distinct adaptive or maladaptive social-cognitive behavioural patterns. We will also measure the level of serotonin in separate PFC and subcortical areas of the rats and will investigate how behavioural endophenotypes relate to differences in serotonin function. In a second step we will generate two new genetic rat models specifically targeting the serotonergic system to examine how the experimental manipulation of serotonin neurotransmission affects the expression of these social-cognitive behaviours in rat.

• DFG Programme: Research Grants
• Participating Persons: Professor Dr. Michael Bader; Professor Dr. York Winter