Lieu : Centre Broca Nouvelle-Aquitaine – salle de conférence
Computational physiology and pathophysiology of the basal ganglia network.
Basal ganglia (BG) are a group of interconnected subcortical nuclei involved in behavior control. The BG network contributes to a broad diversity of brain functions that requires the integration of motor and non-motor information and its dysfunction leads to common human neurological (e.g., Parkinson’s disease) and psychiatric (e.g., obsessive compulsive disorders) disorders.
My research aims to uncover the neural processes underlying BG functions and their malfunction in human disorders. To do so, I combine several experimental approaches including multi-electrodes and multi-site recordings in all major nuclei of the BG of behaving monkeys, behavioral monitoring, chemogenetics and pharmacological lesions. I also employ advanced techniques in digital signal processing to examine the neuronal activity at different spatial resolutions (i.e., local field potential, spiking multi- and single-unit activity) along the BG network in normal and parkinsonian monkeys, as well as in parkinsonian patients undergoing deep brain stimulation.
Up to now, my work contributes to understand how BG network integrates relevant information from the state-encoding thalamo-cortical areas to brain motor centers in order to select/choose and execute appropriate behaviors. However, the neural computation of decision-making in BG network is elusive and does not satisfactorily reflect the complex and known BG anatomy and physiology. Indeed, BG network can be divided into at least two segregated and partially overlapping functional circuits: the ventral and dorsal circuits. Moreover, their normal and pathological functioning during the integration of motor, cognitive and limbic information required during decision-making still needs to be determined.
To bridge this gap, I will (i) characterize the effect of transient and reversible inhibition (using chemogenetic approach) of the information flow in the ventral and dorsal BG circuits on monkey’s decision-making capabilities and (ii) record the neuronal activity of these two functional circuits in behaving monkeys before and after striatal dopamine depletion and induction of parkinsonism.
My project will therefore shed light on the neural computation in the ventral and dorsal BG circuits during decision-making and will force us to revise the classical computational models of the BG. Moreover, it will also allow a better understanding of the consequences of BG dysfunction in Parkinson’s disease on decision-making capabilities, and will help to develop new therapeutic approaches for parkinsonian patients, that no longer essentially concentrate on restoring normal motor behavior but also aim to treat the non-motor symptoms such as decision-making deficits.