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Multi-layered integration of motivated actions and their outcomes in basal ganglia circuits

Project description

Shedding light on basal ganglia neural mechanisms governing action control

Action initiation and suppression are impaired in patients who suffer psychiatric disorders such as depression and impulsivity. A better understanding is needed of the neural basis of such action control. There’s a strong connection between the direct and indirect output pathways of the basal ganglia and action initiation and suppression, respectively. The EU-funded GONOGO project intends to gain insight into the neural mechanisms in the basal ganglia that govern action control. Its novel interdisciplinary approaches will include monitoring neuronal ensemble activity with calcium imaging using implantable, miniaturised fluorescence microscopes and simultaneous optogenetic manipulation in novel transgenic rats performing in a tailor-made behavioural paradigm. The project’s work may help improve treatment of depression and impulsivity disorders.

Objective

We cross the street when the traffic light is green (action initiation), and we wait if it is red (action suppression), both in order to reach a goal across the street, such as getting an ice cream (rewarding) or insect-repellant to avoid a mosquito bite (aversive). Such action control is dysfunctional in several psychiatric disorders. For example, action initiation and suppression are impaired in patients suffering from depression and impulsivity, respectively. Thus, improving our incomplete understanding of the neural basis of action control has translational value, specifically how action outcome valence (rewarding or aversive) interacts with brain mechanisms of action control (i.e. initiation or suppression). The direct and indirect output pathways of the basal ganglia are strongly implicated in action initiation and suppression, respectively, and receive modulating input from dopamine and serotonin neurons, which are implicated in processing rewarding and aversive stimuli, respectively. I hypothesize that the anatomical and functional integration of these opposing systems supports action control as well as constitutes a neural interface for the interaction of action control and outcome valence. I propose to use a set of innovative and inter-disciplinary approaches that include monitoring neuronal ensemble activity with calcium imaging using implantable, miniaturized fluorescence microscopes and simultaneous optogenetic manipulation in novel transgenic rats performing in a tailor-made behavioral paradigm. I aim to understand the neural mechanisms in the basal ganglia that crucially govern the control over actions with different outcome valences. My anticipated results will inform future research and potentially treatment of psychiatric disorders such as depression and impulsivity disorders. Further, this fellowship will strengthen my position as an independent researcher and increase my chances for a tenure-track position at a European research institution.

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Topic(s)

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2019

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Coordinator

ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
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.

€ 187 572,48
Address
MEIBERGDREEF 15
1105AZ Amsterdam
Netherlands

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Region
West-Nederland Noord-Holland Groot-Amsterdam
Activity type
Higher or Secondary Education Establishments
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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.

€ 187 572,48
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