Our current projects are aimed at finding the different modulators of flexible behaviours and identifying the neural bases underlying this modularity. They involve the different members of the team:
1. We will identify the role of the neuronal nicotinic receptors (nAChRs) in the modulation of neurotransmitter release in the prefrontal cortex. (Project of Renata Dos-Santos Coura).It is known that the prefrontal cortex (PFC) receives dopaminergic projection from the ventral tegmental area but also noradrenergic projection from the locus coeruleus, cholinergic projections from the nucleus basalis magnocellularis and serotoninergic projection from the dorsal raphe nucleus. It may therefore be of major interest to establish how the nAChRs participate in the integration of the different neurotransmitters on PFC functions.
2. Identification of the neural partners of the prelimbic prefrontal cortex in flexible behaviors. (Project of Jonathan Chabout).Another important –and controversial- issue in flexible behaviours regards the neurobiological source of the decision switch when conflict between different alternatives exist. This conflict may concern the response selection, the decision to make or the motivation to satisfy (hence, the value of different motivations in competition). The role of the anterior cingulate in conflict at the decision stage, and not at the motor selection stage, has recently been shown in humas, whereas the ventral and dorsolateral PFC and ventral striatum would encode the valence of different behavioural outcomes in a decision-making task. In rodents, the ability to switch task –but not motivation- and to inhibit previously reinforced behaviour has been shown to depend on the orbitofrontal integrity. Thus, even if the circuits involving the different subareas of the PFC and the striatum are certainly crucial to estimate the reinforcement value and response selection, it is not known how the brain circuit exactly allows an appropriate switch between motivations.
3. Relationship between flexible behaviour and impulsive/compulsive traits. (Project of Pierre Serreau)The last major issue for appropriate decision-making in changing situations or contingencies, is the ability to desengage from one current action, i.e. to inhibit previously reinforced behaviours. This aspect consist in the appropriate control of impulsive/compulsive behaviours. In pathologial states, inflexible behaviours have been associated with some other behavioural traits, such as impulsivity, to which some neurobiological markers have been recently associated in humans and in rodents. We will shortly design a task for measuring mice compulsivity in order to test this trait in b2KO mice. We will also study whether some neurobiological markers, like D2/D3 receptors expression, correlate with impulsivity/compulsivity traits.
4. Role of emotions in flexible behaviours (Project of Anne Nosjean).The relationship bewteen the amygdala and the PFC has not been studied regarding flexible behaviours. We will thoroughly investigate the anatomical and functional PFC-amygdala connections in WT and b2KO mice in behaviours affected by stress.