1. Institute of Neurodegenerative Diseases CNRS-Université Victor Ségalen-Bordeaux 2 thomas.boraud@u-bordeaux2.fr Thomas Boraud MD, PhD Neural substrates of motivated behaviours

2. Research Topics Cellular Degeneration Parkinsonian Syndroms Synaptic Plasticity and Pathology Interaction between receptors and neurotransmitters Neural networks on simplified preparations Dynamic properties of cortex-basal ganglia loops Functional Reorganization in pathological conditions Control mechanisms Protein Agregats - regulation Genetic and environmental models Pathophysiology from the network to the cellular signaling LID & ICD – Relationship with addiction and modelisation Development and preclinical validation of new therapeutic approaches Ecological, Genetic, Pharmacological and/or Surgical approaches Clinical Studies Cognition - Dementia Physiology et pathophysiology of cortex-basal ganglia loops Animal Models, Electrophysiology, Imaging Clinical Research

3. Vertical and Translational Approach Neurotransmitter Receptors Subtypes Interactions Channel Subcellular Signaling Cascade Morphology Neuronal Phenotype Electrophysiology Transcriptional Activity Network Level Behaviour Cellular Level Metabolic Marker Imaging Plasticity Electrophysiology Target Acquisition & locking Behavioural Studies

4. Longitudinal Approach 100 0 Time % of neurones Presymptomatic Symptoms Honeymoon Stable phase Diagnosis Decompensation Aging Neurodegenerative Disorders 2 3 5 4 1 Early (perinatal?)

5. 10 Research Teams Approche systémique de la boucle extrapyramidale T. Boraud Monoamines, Stimulation cérébrale profonde et maladie de Parkinson A. Benazzouz Oscillations Neuronales dans le réseau des Ganglions de la Base B. Bioulac (transition) Addiction, compulsion et syndrome de dysrégulation dopaminergique S. Ahmed Physiologie et physiopathologie des relations thalamo-frontales P. Burbaud Physiopathologie des syndromes parkinsoniens E. Bezard Neurogénétique et vieillissement dans les maladies neurodégénératives C. Lo Bianco Approches innovantes pour la prise en charge des maladies neurodégénératives C. Gross Régulation Moléculaire des Récepteurs Synaptiques E. Boué-Grabot Dynamique des réseaux neuronaux et vasculaires dans les processus mnésiques B. Bontempi

6. Methods Multiple Electrode Recordings Juxta-Intra and Extracellular Recordings Behavioral Studies in Rodents and Primates Electrochemical detection Theoretical approach Neural substrates of motivated behaviours Research Topics Dynamic Properties of the CBG Loop Dopamine and associated pathologies Physiology of Decision Making CUE GO 025%33%40%60%67%75%100% PETHs P values PETHs Raster Peth Cue Go Analysis method 200 ms Normalisation [Response – basal] Relevant neural information

7. Example: Role of the CBG loop in decision maling process A B P( ) =1 P( ) =2/3 C D P( ) =1/3 P( ) =0 P( ) A A A A A B B B B B Cortex Striatum GPi STN Thalamus 0 1.4 n=235 * Learning Model Pathophysiogy, etc…