Our research is interested in the neural, cellular and molecular substrates of inter-individual vulnerability to develop impulsive / compulsive disorders such as drug addiction, Obsessive / compulsive disorders, Tourette’s syndrome, pathological gambling or dopamine dysregulation syndrome in Parkinson Disease.
Our working hypothesis is that impulses, originating from the amygdalo-insular networks can drive the behavior through explicit knowledge involving prefrontal and orbitofrontal loops or implicit mechanisms that instead depend upon the functional relationships of these structures with several domains of the striatum (see figure 1: The neurobiological substrates of incentive habits).
We suggest that inter-individual vulnerability to develop impulsive / compulsive neuropsychiatric disorders stem from aberrant plasticity processes within the corticostriatal networks governing the translation of impulses into actions that ultimately result in a so-called abnormal incentive habit process (see figure 1, after Belin & Everitt, in Handook of the Basal Ganglia, 2009).
Our research is designed according to a vertical, top-down strategy with direct translational perspectives, that combines the development of refined preclinical models of impulsive and compulsive behaviours, causal manipulations of the brain with either pharmacological tools or optogentics, correlational analyses of the brain using state of the art molecular biology techniques.
Our program, developed in tight collaboration with Pr Barry Everitt’s group, is subdivided in several converging lines of research:
1. The role of the insular cortex, and its interactions with the BLA and the ventral striatum, in drug addiction and OCD within a general framework of impaired insight in compulsive disorders
2. The functional interactions between the amygdala nuclei and the different domains of the striatum subserving the establishment of aberrant incentive habits and subsequent compulsivity
3. The cellular and molecular substrates of intrastriatal shifts subserving maladaptive habits
4. The influence of the environment on inter-individual differences to develop impulsive / compulsive disorders
For this we use several complementary techniques ranging from experimental psychology to molecular neurobiology:
Protracted self-administration, habitual and compulsive drug (cocaine, heroin and alcohol) seeking and taking behaviours, schedule-induced polydipsia, 5-choice serial reaction time task, differential low rate of reinforcement, fixed chain number schedule of reinforcement, rat gambling task, reversal learning, novelty preference, interoceptive discrimination task, sign tracking, inter individual differences
Causal manipulations of the brain in behaving animals: neuropharmacology, optogenetics
Extracellular electrophysiology; patch-clamp electrophysiology
Cellular and molecular neurobiology
Cell culture, RNA seq, in situ hybridization, western-blot, ChiP-ChiP hybridization
Enriched environment vs stress