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

Información del proyecto

AmygdalaNeuroMod

Identificador del acuerdo de subvención: 843236

DOI

10.3030/843236

Proyecto finalizado el 31 Octubre 2022

Fecha de la firma de la CE 19 Marzo 2019

Fecha de inicio 1 Junio 2021

Fecha de finalización 31 Mayo 2023

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 191 149,44

Aportación de la UE

€ 191 149,44

Coordinado por

FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Switzerland

Periodic Reporting for period 1 - AmygdalaNeuroMod (Unraveling the combinatorial logic of amygdala neuromodulation in decision-making and learning.)

Período documentado: 2021-06-01 hasta 2023-05-31

Resumen del contexto y de los objetivos generales del proyecto

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.

In this work, we studied the functional role of neuromodulatory inputs to the amygdala circuitry.

Towards this goal, we combined our experience in large-scale electrophysiology and modern genetic tools and neurotechnologies to record and manipulate the activity of dopamine, serotonin, norepinephrine and acetylcholine inputs to the amygdala during behavior in behaving mice. Using this approach, we characterized the influence of neuromodulators in the amygdala and demonstrated their role in defining network activity, behavioral state, and learning.

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

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

In the context of this project, we performed anatomical tracing, functional fiber photometry recordings of neuromodulatory centers and their projections to the amygdala, as well as optogenetic manipulations of the same neurons.

We combined these experiments with large-scale electrophysiological recordings from amygdala neurons in behaving mice, to study the interaction of neuromodulators with the amygdala activity.

This work was presented in major conferences in the field, including the Ascona Neural Circuits Meeting 2022, the 13th FENS Forum 2022, and the Giessbach Meeting 2021.
Parts of this work have resulted in one publications so far (Massi et al. 2023) and several upcoming publications that are still in the preparatory phase.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

The work performed in the context of this project has provided novel data and insights on the coordination of two major brain systems, the amygdala - a core region for emotional processing - and the four major neuromodulatory systems.

This work is unprecedented, given that so far researchers have typically investigated these systems separately, not incorporating the combinatorial aspect of the diverse neuromodulatory innervation of the amygdala.

Although at the moment we are still at the beginning of understanding these processes, elucidating the role of different neuromodulatory inputs to specific brain regions holds the keys to understanding and treating mood disorders.
Given the severity and cost of mental health disorders for the EU society and economy (~240 billion € direct and indirect costs), it is imminent to address these fundamental questions.
The answers will contribute to our understanding of the substrate underlying physiological and pathologic brain states and will guide the design of human and clinical studies and the development of therapeutic strategies.

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