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Tuning claustrum circuits to restore cognitive function

Objective

Cognitive dysfunction is a major contributor to disability in several neurodevelopmental and psychiatric disorders, including schizophrenia, autism spectrum disorder and attention deficit hyperactivity disorder. These conditions often involve deficits in executive functions such as working memory, cognitive flexibility and attentional control. Despite their impact on daily functioning, current medications largely rely on global neurotransmitter modulation and remain only modestly effective at improving cognitive symptoms.

Our ERC-funded work identified a genetically defined population of glutamatergic projection neurons in the claustrum (CLA) that plays a key role in executive behavior. Manipulating these neurons in adult wild-type mice reproduces cognitive and physiological deficits observed in mouse models of neurodevelopmental disorders. Conversely, restoring CLA neuronal activity in adulthood rescues neural activity in both the CLA and prefrontal cortex and restores behavior, including working memory and cognitive flexibility. These findings suggest that cognitive dysfunction may arise from reversible instability within CLA circuits.

The CLAUSTUNE project will translate these findings into a proof of concept by testing whether CLA circuits can be therapeutically targeted to restore cognitive function. We will first determine whether systemic administration of a candidate therapeutic compound identified through our work can restore CLA neuronal activity and improve cognitive flexibility in a genetic model displaying intrinsic CLA dysfunction. We will then determine whether targeted modulation of claustrum neurons can restore executive performance in an independent mouse model of neurodevelopmental disorder characterized by CLA circuit dysfunction. By evaluating pharmacological and circuit-based interventions across distinct disease models, CLAUSTUNE will assess whether the claustrum can function as a therapeutic control node for restoring cognitive function.

Fields of science (EuroSciVoc)

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2026-POC

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Host institution

UNIVERSITE DE GENEVE
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.

€ 150 000,00
Address
RUE DU GENERAL DUFOUR 24
1211 Geneve
Switzerland

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Region
Schweiz/Suisse/Svizzera Région lémanique Genève
Activity type
Higher or Secondary Education Establishments
Links
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.

No data

Beneficiaries (1)