Institut des Neurosciences cellulaires et intégratives (INCI) CNRS UPR 3212
Intitulé de l’équipe : Neuroanatomie, douleur et psychopathologies
Responsable de l’équipe: Ipek Yalcin / Michel Barrot
E-mail : firstname.lastname@example.org
Téléphone : 03 88 45 66 33
Site web éventuel : inci.u-strasbg.fr
Nom du Directeur de thèse : Michel BARROT : Jennifer KAUFLING
Téléphone : 03.88.45.66.56
Context: The pleasant or unpleasant nature of an event can be influenced by our emotional state. This state of mind, or mood, influences the perception of our environment and of life events, and raises the question of its biological bases. Ventral tegmental area (VTA) dopaminergic (DA) neurons are a key element involved in evaluating the emotional and motivational value of a stimulus, which makes them a key component of motivated and adaptive behaviours. Understandably, DA neurons are thus involved in psychopathologies associated with perturbations of emotional or hedonic states such as substance dependence or depression. Recent understanding of the physiology of these neurons has highlighted the major impact of the balance between their inhibitory and excitatory afferents. This balance of regulation, particularly GABAergic (GABA)/glutamatergic (GLU), seems to be fundamental in DA neurons capacity to appropriately integrate information. Our previous work, for instance revealed a major influence of this regulatory balance in the affective state associated with protracted morphine withdrawal.
Hypothesis : We then hypothesize that alterations of the equilibrium between GABA and GLU afferents of VTA DA neurons contribute to a negative affective state by modifying the capacity of these DA neurons to treat information in a bidirectional way: negative and positive. Such a mechanism could participate in behavioural abnormalities associated with protracted morphine withdrawal but in a broader framework, it could also contribute to the devaluation of positive events leading to anhedonia, which is the inability to feel pleasure in situations previously considered pleasant, a symptom especially found in depressed states. The general goal of this project is thus to identify the alterations of VTA DA neuron activity in animal models of anhedonia.
Specific aims and techniques: The first objective will be to understand the consequences of anhedonic states on the regulation of VTA DA neurons, and more precisely on the GABA / glutamate balance. This will be study using in vivo single cell electrophysiological recordings of VTA DA neurons as well as GABAergic and glutamatergic neurons regulating the activity of these DA neurons in two animal models of anhedonia: protracted opiate withdrawal and anxio-depressive state induced by chronic neuropathic pain. The second objective will be to determine the impact of these anhedonic states on the ability of DA neurons to encode a rewarding or aversive stimulus. This will be achieved through electrophysiological recordings in the awake head fixe mice involved in behavior.
Wished skills: The candidate should have a solid background in neuroscience. Background in behavioral or electrophysiological approaches will be appreciated. The project involves working on live animals (mice).
Expertises which will be acquired during the training: The proposed project will provide expertise in neurophysiology of dopaminergic systems and circuits regulating these neurons, as well as in depression and pain. On a technical aspect, this project will provide the candidate with skills in stereotaxic surgery, rodent behavior, optogenetics and in vivo single cell electrophysiology in anesthetized and awake mice.
Key word : Dopamine, pain, depression, electrophysiology