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Neurobiology of Decision-making

Group leader : Sylvie Granon

The execution of behaviors appropriate in time and space require the subject to produce successive planned actions for which he has to estimate costs and benefits. Beside the impact of motivations which guide its behavior, these actions integrate external stimuli, autobiographical parameters (through memory processes) and emotional features. In everyday life situations, making choices request to deal with concurrent motivations. Decision-making processes are efficient when the subject is able to integrate appropriately the value of reinforcements (benefits) which he anticipates.

Besides, its ability to disengage from routine behaviors (control of impulsive or compulsive behaviors) and its ability to alternate between different motivations in a balanced way are fundamental components of successful decision-making processes. Different components participate in the construction of appropriate decision-making during complex behaviors. In a context of uncertainty, decision-making processes allow flexible and adapted behaviors encompassing environmental, motivational or emotional changes. These highly adapted behaviors are impaired in all psychiatric disorders, even if they do not all depend on the same neurobiological, neurochemical or genetic systems. Indeed, the basic components of flexible behaviors may be affected independently in mental disorders, the final effect being non adapted behaviors.

In this context, the team aims at indentifying the neural bases of flexible behaviors in uncertain environments. We model these behaviors in mice. This animal model allows the control and modulation of environmental, emotional and motivational features of a situation. Furthermore, it allows fine-tune behavioral dissections as well as a molecular and genetic analysis, thanks to numerous mice model available. Our experimental results obtained in mice has shown a dissociation of the basic components of flexible behaviors, and thus allow now the study of the impact of the different modulators on such components. These dissociations suggest that an integrator, for which neural, neurochemical and genetic bases are yet to be undermined, which would contribute to temporally coordinate the basic components of flexible behaviors together. On a neurobiological point of view, it is acknowledged that the prefrontal cortex -PFC- plays a crucial role.

A large part of our work has been to set up original behavioral paradigms specific to mice in order to target these behaviors. These paradigms has allow the characterization of cognitive deficits of mutant mice deleted for the beta2-nicotinic neuronal receptor -b2KO mice.

Two paradigms have been successfully developed during the past six years :

- a social interaction task which put in competition several natural motivations : spatial novelty exploration, social contact and food motivation. This paradigm increase the frequency of decisions to be made because it increase the level of uncertainty to which the subject faces but also allow us to manipulate and modulate the value of each reinforcement.

- an operant conditioning task which allows the measure of impulsivity in mice. This protocol , originally designed by Sandra Suarez and myself, has been developped by Pierre Serreau, during his Master degree and his PhD.

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