institute of neurodegenerative diseases cnrs-université victor ségalen-bordeaux 2...
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Institute of Neurodegenerative DiseasesCNRS-Université Victor Ségalen-Bordeaux 2
Thomas Boraud MD, PhD
Neural substrates of motivated behaviours
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
Vertical and Translational Approach
Neurotransmitter
ReceptorsSubtypesInteractions
Channel
Subcellular Signaling Cascade
MorphologyNeuronal Phenotype
ElectrophysiologyTranscriptional Activity
Network Level
Behaviour
Cellular Level
Metabolic MarkerImagingPlasticity
Electrophysiology
Target Acquisition &locking
Behavioural Studies
Longitudinal Approach
100
0
Time
% o
f n
euro
nes
Presymptomatic
Symptoms
HoneymoonStable phase
DiagnosisDecompensation
Aging
Neurodegenerative Disorders
2
3
54
1
Early (perinatal?)
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
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
0
25%
33%
40%
60%
67%
75%
100
%
PETHs P values
PETHs
0 100 200 300 400
0
0.25
0.5
0.75
1
Trials
Pa
1
Optimal learning
Raster
Peth
Cue Go
Analysis method
200 ms
Normalisation [Response – basal]
Relevant neural information
Example: Role of the CBG loop in decision maling process
AB
P( ) =1P( ) =2/3
CD
P( ) =1/3P( ) =0
P( )
A
A
A
AA
B
B
B
B B
Cortex
Striatum
GPi
STNThalamus
0 100 200 300 400
0
0.25
0.5
0.75
1
Trials
Pa
1
Optimal learning
0 50 100 150 200 250 300
0
0.25
0.5
0.75
1
Trials
PA
1
No learning
0
1.4n=235
*
Learning ModelPathophysiogy, etc…