Unraveling the combinatorial logic of amygdala neuromodulation in decision-making and learning.

Description du projet

L’amygdale et le traitement des troubles de l’humeur

La dépression, l’anxiété et presque tous les autres troubles mentaux sont associés à un déséquilibre neuromodulateur dans des sous-circuits particuliers. Le traitement des troubles de l’humeur exige dès lors une compréhension plus approfondie des différentes entrées neuromodulatrices dans des régions spécifiques du cerveau. Le projet AmygdalaNeuroMod, financé par l’UE, s’intéressera à l’amygdale, qui joue un rôle clé dans la régulation des émotions. Plus particulièrement, le projet étudiera le rôle fonctionnel des entrées neuromodulatrices dans les circuits de l’amygdale dans les processus d’apprentissage et de prise de décision. Les résultats mettront en lumière la logique des interactions entre les neuromodulateurs et leur mise en œuvre au niveau de circuits et de types de cellules particuliers dans l’amygdale.

Objectif

Proper neuronal circuit function depends fundamentally on the balance of neuromodulators, a set of neurotransmitters released widely throughout the brain. Almost every mental disorder, including anxiety and depression, that affect one out of four Europeans, are associated with a neuromodulatory imbalance in specific sub-circuits. Elucidating the role of different neuromodulatory inputs to specific brain regions holds the keys to understanding and treating mood disorders.

The amygdala plays an essential role in the processing of emotional stimuli and salience, ranging from reward to threat and synaptic alterations in this region are critical for learning and emotional processing. Amygdala is innervated by every major neuromodulator, yet surprisingly little is known about the activity of these inputs under physiological conditions and how neuromodulation regulates amygdala circuit activity during different behavioral states and learning.

Here, I propose to study the functional role of neuromodulatory inputs to the amygdala circuitry during learning and decision-making. Towards this goal, I will combine my experience in large-scale electrophysiology with the expertise of the host laboratory in modern genetic tools and neurotechnologies to simultaneously record and manipulate the activity of dopamine, serotonin, norepinephrine and acetylcholine inputs to the amygdala during context-guided decision-making in behaving mice. Using this approach, I aim to characterize the logic of interactions between neuromodulators and its implementation at the level of defined circuits and cell types in the amygdala and to demonstrate the role of this coordination in defining network activity, behavioral state and learning.

The fellowship will contribute to our basic understanding of the interplay between two core brain systems, while it will provide me with a unique opportunity to expand my expertise and establish the foundations of my future career as an independent group leader.