Molecular mechanisms controlling neuronal circuits for decision-making

• Applicant: Dr. Alessandro Filosa
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 398216457

Decision-making is the process to choosing an action among a set of two or more alternatives. The molecular, cellular, and circuit events leading to a decision are still not fully understood. In particular, we know very little about the causal links between events happening at different scales. How do subcellular changes in molecular signaling induce macroscopic effects on neuronal circuits controlling decision-making? The objective of this project is to contribute to answer this question by studying the circuits guiding simple decisions in the larval zebrafish, a model organism with a small and translucent brain which allows to use powerful imaging and genetic techniques to monitor and manipulate the activity of large groups of neurons in vivo. Two important decisions animals often face are whether to approach a food source or avoid potential predators. Motivation and internal states, such as fear and hunger, strongly influence this type of choices. For example, we previously showed that hungry zebrafish larvae take more risks when looking for food, approaching more often ambiguous but possibly edible objects. We also showed that at the neuronal level, this modulation occurs at very early stages of visual processing, and involves the serotonergic system and the hypothalamus-pituitary-interrenal axis, a pathway chiefly involved in responses to stress. We now want to understand how molecular events regulating neuronal excitability in a subset of neurons modulate function of these neuronal circuits. To this end, we plan to carry out a series of behavioral and functional brain imaging studies in zebrafish harboring a mutation disrupting one of these intracellular signaling pathways. Furthermore, we will investigate how activity of neurons affected by these molecular alterations control neuronal circuits underlying approach/avoid decisions. This project will lead to a better understanding of the neuronal circuits guiding decision-making by revealing mechanisms translating the needs and motivation of an animal into the molecular and neuronal events regulating behavior.

• DFG Programme: Research Grants