Our research is interested in the neural, cellular and molecular substrates of inter-individual vulnerability to develop impulsive/compulsive disorders such as drug addiction or Obsessive-compulsive disorder. Our working hypothesis is that impulses, originating from the amygdalo insular networks can drive behavior through explicit knowledge involving prefrontal and orbitofrontal loops or implicit mechanisms that instead depend upon the functional relationships of these structures with several functional domains of the striatum.
We suggest that the individual vulnerability to develop impulsive/compulsive neuropsychiatric disorders stems from aberrant plasticity processes within the corticostriatal networks governing the translation of impulses into actions that ultimately result in an incentive habit.
Our research is designed according to a vertical, top-down strategy with direct translational perspectives. It stems from a unique combination of contemporary techniques ranging from experimental psychology to causal manipulations of the brain with selective pharmacological tools, DREADDS or optogenetics and correlational approaches of brain function using state of the art molecular biology and electrophysiology techniques.
Our program is subdivided into several converging lines of research:
1. The role of the insular cortex, and its interactions with the BLA and the ventral striatum, in habits, drug addiction and OCD.
2. The nature of the functional interactions between the amygdala and the striatum subserving the establishment of compulsive incentive habits.
3. The cellular and molecular substrates of intrastriatal shifts subserving incentive habits.
4. The influence of the environment on individual differences in the vulnerability to develop impulsive/compulsive disorders.
Techniques and approaches:
1. Behaviour: characterisation of inter-individual differences in:
- State of the art chronic cocaine, heroin or alcohol self-administration in the rat measuring reinforcement, escalation, but also drug seeking, may it be goal-directed, habitual or compulsive, using sophisticated schedules of reinforcement and preclinical models
- Compulsive behaviour, as measured in a Schedule-Induced polydipsia procedure
- Impulsivity, as measured in the 5-Choice Serial reaction Time Task, DRL, FCN and delay discounting task
- Decision making, as measured in a Rat Gambling Task
- Anxiety, as measured in Open fields and Elevated Plus Maze
- Locomotor reactivity to novelty, and novelty preference, as measured in novelty-induced CPP tasks
- working memory and behavioural flexibility, as measured in T-maze based tasks and operant tasks
- Sign tracking
- Drug discrimination
2. Circuits
2.i Causal manipulations of the brain in freely moving rats, including:
- Chemo- and optogenetic manipulation of specific pathways
- Pharmacological manipulation of specific brain regions using intracerebral infusions
2.ii In vivo electrophysiological recording of single units and LFPs in anaesthetised rats
3. Cellular and Molecular Biology
- in situ hybridisation
- RNAscope
- qPCR
- western-blot
- cell culture
- immunohistochemistry
