GONOGO · Multi-layered integration of motivated actions and their outcomes in basal ganglia circuits
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-10-01 → 2022-09-30
- EU contribution
- €187,572
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Multi-layered integration of motivated actions and their outcomes in basal ganglia circuits
We adapt our actions to situational demands and outcomes we desire. Motivated actions are driven by the valence of their outcome, which can be rewarding (positive valence) or aversive (negative valence), wherein we are inertly biased to actively pursue rewards and passively avoid aversive stimuli (Fig 1). This action bias is beneficial in many situations but makes it difficult to inhibit action in rewarding situations that require patience and initiate action to avoid aversive events. I aimed to study the neurobiological underpinnings of such valence-driven action selection in the basal ganglia (BG), a brain network consisting of two major pathways that are thought to govern action selection. Such action control is dysfunctional in patients with impulsivity disorders (e.g., behavioral or drug addictions) and depression, where action initiation for rewards is impulsive and action suppression is exaggerated under aversive conditions, respectively. Furthermore, as the proposal addresses a behavioral aspect that is often impaired in patients with psychiatric disorders, the results from this study will be useful in furthering research in psychiatric patients. Specifically, to translate clinical findings from studies in humans into relevant animal models and vice versa, I am engaged in a group project with several clinical psychiatrists, psychologists, and clinical researchers. The overall objective of this proposal was to identify causal mechanisms within the brain that underly action control using cutting-edge technology. This technology gives us a microscopic view of the brain that we can track the activity at the level of single neurons. Thereby, allowing us to understand how groups of neurons work together to achieve the intended behavior.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
- ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM · AmsterdamCoordinatorNetherlands
Links
Data: CORDIS, © European Union