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Cellular substrate of abnormal network maturation in neuropsychiatric disorders

Objective

The long-lasting burden of major neuropsychiatric disorders results from disruption of cognitive performance in daily life. Impairment of long-range coupling between prefrontal cortex and hippocampus represents the substrate of disease-specific mnemonic and executive deficits. While it has been hypothesized that this impairment emerges long before the first clinical symptoms, technical and ethical limitations of non-invasive investigations in high-risk infants precluded the elucidation of ontogenetic mechanisms underlying the pathophysiology of disease. In previous studies, I pioneered the investigation of long-range coupling in the immature brain by developing a multidisciplinary approach that combines electro- and optophysiology in vivo with behavior, anatomy and analysis of network dynamics. Using mouse models of disease’s etiology, we recently identified the de-coupling of prefrontal-hippocampal networks during early development as potential mechanism underlying adult circuit dysfunction. These findings represent the basis for the current proposal, which aims at understanding the cellular mechanisms accounting for abnormal network maturation in neuropsychiatric disorders. First, the role of excitation/inhibition imbalance in the neonatal prefrontal cortex for disease-specific network impairment will be assessed. Second, the synaptic organization and wiring deficits within neonatal prefrontal-hippocampal networks will be monitored. Third, the cellular substrate of abnormal hippocampal activity causing weaker prefrontal-hippocampal interactions will be ascertained. Finally, the identified cellular elements underlying early network dysfunction will be selectively manipulated to rescue the juvenile circuit function and behavioral performance. Understanding the mechanisms of network dysfunction during early development may open new therapeutic perspectives that, when initiated before the onset of clinical symptoms, may improve the devastating outcome of disease.

Fields of science (EuroSciVoc)

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Keywords

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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.

ERC-COG - Consolidator Grant

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Call for proposal

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(opens in new window) ERC-2015-CoG

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Host institution

UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF
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.

€ 2 000 000,00
Address
Martinistrasse 52
20251 Hamburg
Germany

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Region
Hamburg Hamburg Hamburg
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.

€ 2 000 000,00

Beneficiaries (1)

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