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Combinatorial neuromodulation of internal states

Project description

Decoding neuromodulation in brain circuitry

Our daily experiences, shaped by internal states like sleepiness, hunger, fear, and happiness, influence our behaviour and decisions. These states are governed by specific activity patterns in neural circuits, modulated by neuromodulators such as dopamine, serotonin, and norepinephrine. These chemicals, released across various brain regions, affect the functioning of target circuits. Disruptions in the balance of these neuromodulators are linked to mood disorders, prompting therapeutic efforts to restore equilibrium. The ERC-funded StateNeuromod project studies how combinations of neuromodulators influence brain function, particularly within the hippocampus-prefrontal circuit, crucial for cognition and memory. Using advanced techniques, the project seeks to uncover the neuromodulatory landscapes shaping behavioural states, neuronal dynamics, and circuit organisation in behaving mice.

Objective

Being sleepy, hungry, afraid, or happy impacts our daily experience and defines our behavior and actions. Such internal states are characterized by unique signatures of activity across neural circuits and are actively shaped by neuromodulators, such as dopamine, serotonin, acetylcholine, and norepinephrine, that are released widely throughout the brain to alter the function of target neural circuits.

At any moment, distinct combinations of neuromodulators are being released in each brain region. Changes in the neuromodulator balance have a powerful impact on the brain-wide configurations that underlie internal and behavioral states, while most mood disorders are associated with neuromodulator imbalance, and most therapeutic strategies attempt to restore this balance. However, how combinations of neuromodulators define distinct brain configurations and shape internal states remains unknown.

The prefrontal cortex and the hippocampus are two interconnected regions, which are essential for cognitive processing and memory. They receive converging neuromodulatory inputs, and synaptic alterations in these regions are critical for learning, while dysfunction of this pathway is involved in most mood disorders. Despite the vital role of these circuits for brain function, little is known about how combinatorial neuromodulation regulates circuit configuration and coordinates information flow between these regions.

In this project, we will combine neuromodulator monitoring with large-scale in vivo electrophysiology, optogenetics, and in vivo genome editing to answer the following questions and resolve the contribution of neuromodulators to the organization of neuronal ensembles and information gating in the hippocampus-prefrontal circuit in behaving mice.

1. What is the neuromodulatory landscape across behavioral states?
2. How does state-specific neuromodulation sculpt neuronal dynamics?
3. What are the circuit elements underlying combinatorial neuromodulatory action?

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Programme(s)

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-STG

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Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 297 063,00
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 499 563,00

Beneficiaries (2)

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