Prénom : Paul
Téléphone : 04 91 32 40 54
Fonction : Chercheur
Grade : DR2
Bureau : 0.03


My research interests focus on the neuronal mechanisms that underlie our ability to learn associations between stimuli and outcomes, processing of reward-related information, and selection of actions. These processes depend on a distributed network of cortical and subcortical regions in the brain. Among these are the basal ganglia, a group of subcortical nuclei, whose main component is the striatum. This structure is a major site of integration of a variety of information that originates from the cerebral cortex, thalamus, and limbic system, under the modulatory influence of midbrain dopamine neurons. A wide range of human diseases are associated with dysfunction of the striatum, including movement disorders such as Parkinson’s disease, Huntington’s disease, and dystonia, neuropsychiatric disorders such as compulsive disorders, including Tourette syndrome and various forms of addiction.

The striatum can be functionally divided along a dorsolateral/ventromedial axis, based on its afferent connections with cortical areas and limbic system, thus defining specific functional subregions involved in motor, cognitive and motivational processes. Greater knowledge about how striatal circuits participate to adaptive behavior may have an impact on our understanding of the causes of striatal-based disorders in humans, bringing us closer to the ability to develop new therapies.

The striatal circuitry consists of projection neurons, which represent the vast majority of neurons and form the striatal output, intermingled with a variety of GABAergic interneurons and a rather homogeneous population of cholinergic interneurons. It is widely accepted that parvalbumin-containing GABAergic interneurons and cholinergic interneurons can be distinguished on the basis of their electrophysiological properties, the former corresponding to fast-spiking interneurons (FSIs), the latter to tonically active neurons (TANs), and they are both crucial regulators of striatal output pathways. Using an electrophysiological approach in behaving macaque monkeys, we investigate how striatal function relates to distinct processes underlying behavior, with an emphasis on the contribution of local circuit components (i.e., TANs and FSIs). This kind of basic research must help us to clarify how specific microcircuits participate in striatal information processing in health and disease.

With my collaborators (K. Marche and A.-C. Martel), I am currently pursuing four lines of investigation :

1. The role of the striatum in the evaluation and selection of actions in the context of reward uncertainty (K. Marche, P. Apicella) in collaboration with :
- E. Coutureau, A. Marchand (Aquitaine Institute for Cognitive and Integrative Neuroscience, Bordeaux)
- E. Procyk (Stem-cell and Brain Research Institute, Bron)
- B. Girard, M. Khamassi (Institute of Intelligent Systems and Robotics, Paris)

2. Interactions between striatal cholinergic interneurons (TANs) and midbrain dopamine neurons during learning (K. Marche, A.-C. Martel, P. Apicella)

3. Striatal GABAergic interneurons (FSIs) and motor control (K. Marche, P. Apicella)

4. Temporal information processing in the striatum (A.-C. Martel, P. Apicella)

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