Project description
Serotonin and controllability estimation in health and disease
The body does an amazing job of self-regulation, maintaining stable and favourable conditions while adapting to a changing environment. Beyond regulating body temperature and heart rate, cognitive and motor processes are also controlled. The brain is often seen as a complex controller of these processes, but not all environments are controllable to the same extent. Estimation of this ‘controllability’ may play a key role in health and disease, yet the cognitive and neurobiological substrates of this are not known. The ERC-funded CRACK-5HT project will investigate the cross-species regulation of action via controllability estimation on the hypothesis that the activity of serotonergic neurons encodes controllability prediction errors. Outcomes may help clarify the role of serotonin in depression.
Objective
Knowing the causal structure of a system enables controlling this system to our benefit. In neuroscience, the brain is widely envisioned as a complex controller whose main role is to help the organism reach and maintain itself into the most desirable states of its environment. However, not all environments are equally controllable and changes in environmental controllability require a permanent adaptation of cognitive and motor processes. Controllability estimation may thus play a key role in the regulation of action in health and disease, but its cognitive and neurobiological underpinnings remain poorly understood. Here, I will leverage a computational framework that I have recently developed to investigate in detail the neural implementation and the downstream consequences of controllability estimation for adaptive and maladaptive behaviours, with a particular focus on the serotonin (5-HT) system. My goal is to demonstrate that 5HT neurons broadcast controllability prediction errors and mediate the behavioural effects of controllability estimation in rodents and humans performing homologous tasks. To do so, I will record and manipulate the activity of genetically defined 5-HT neurons using light-based techniques and pharmacological manipulations. I will further test whether drug-nave patients diagnosed with depression suffer from downward biases in controllability estimation and whether these biases can be alleviated by the initiation of serotonergic antidepressants. Finally, I will probe the neural mechanisms underlying controllability estimation mechanisms in healthy and depressed participants using functional neuroimaging. The ambition of this translational project is to untangle the complexities of 5-HT signalling and clarify its roles in depression and antidepressant treatments, which are still elusive despite decades of research. As such, it may provide new insights and predictive phenotyping tools for evidence-based approaches in neuropsychiatry.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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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)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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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
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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 - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-STG
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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.
75654 PARIS
France
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