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

Projektinformationen

AmygdalaNeuroMod

ID Finanzhilfevereinbarung: 843236

DOI

10.3030/843236

Das Projekt endete am 31 Oktober 2022

EK-Unterschriftsdatum 19 März 2019

Startdatum 1 Juni 2021

Enddatum 31 Mai 2023

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten

€ 191 149,44

EU-Beitrag

€ 191 149,44

Koordiniert durch

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.)

Berichtszeitraum: 2021-06-01 bis 2023-05-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

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.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

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.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

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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