Project: Understanding decision making from the dynamics of large neural populations in behaving zebrafish

One of the central goals in brain research is the elucidation of the dynamic interactions among neurons and circuits underlying cognitive processes. In this project we focus on decision making as an essential element of cognition. We propose a multidisciplinary systems biology approach towards the understanding of the neuronal network mechanisms underlying decision making in behaving zebrafish. To study how simple decisions are represented and processed in the nervous system, we shall present to naïve zebrafish larva ambiguous visual stimuli (stimuli that induce two possible behaviours with similar probabilities). This type of stimulus always evokes similar patterns among sensory circuits, but depending on the behavioural choice, very distinctive ones among networks involved in decision making. To that end, the activity of large neuronal networks and behaviour will be simultaneously monitored, using a two-photon Ca2+ imaging custom-built system. Both behaviour and circuit activities will be analysed using decision-making theory, information-theory tools, and biophysical circuit models. Using these tools, we shall identify ?network functional states? and ?cell-specific states?. We shall also examine the role of spontaneous activity in the brain. Ongoing activity, once interpreted as irrelevant random noise, has been found to exhibit highly coherent spatiotemporal patterns suggesting a possible role in cognition. To examine the role of ongoing spontaneous activity on the decision, we shall test the idea that decisions result from the interaction between the internal state of the brain and the activity evoked by external sensory stimulation. Finally, we will perform experiments in zebrafish modelling neurological disorders and addiction (e.g. Parkinson and amphetamine addiction) and then, expecting to provide a quantitative understanding of the impact of these diseases on decision making at both behavioural and neuronal circuit levels.

Acronym	Zebrain
Project Results (after finalisation)	Animals constantly need to select among several choices. How decision-making takes place at the level of neuronal circuits and animal behaviour is an important question for our understanding of brain function. But brains are active all the time, even in absence of stimuli, with an important spontaneous ongoing activity. What is the structure and role of this spontaneous activity? We decided to take this question to a new level by considering the brain of the zebrafish larva as we had access to thousands of individual neurons and could then relate their spontaneous activity to behavioral outcomes. To address this question, we generated lines of zebrafish to study the calcium activity, a proxy of neuronal firing, and recorded its changes using genetically encoded fluorescence reporters. Using techniques from Information Theory and Machine learning, we analyzed the spontaneous activity of neuronal circuits and found that it has a topological structure that corresponds to preferred states best for prey detection. Spontaneous activity is thus proposed to be ready-to-fire states that best prepare the animal for the most relevant behaviours for survival. Additionally, we have studied the spontaneous behaviour of the animals and found that there is a strong individuality stable across days and that decision-making is best understood in a social context for the juvenile zebrafish, and we have obtained new data acquisition methods and mathematical models to characterize these spontaneous and evoked behaviours. The study of individuality, sociality and their relation to ongoing activity in zebrafish is thus giving us the opportunity to have a deeper understanding of the relations between circuit activity and behaviour at the resolution of neurons. This deeper understanding is also helping us to better understand disease, in our case a model of Rett syndrome in zebrafish.
Network	ERASysBio+
Call	ERASysBio+-2008-01

Project partner

Number	Name	Role	Country
1	Cajal Institute (CSIC)	Coordinator	Spain
2	Ecole Normale Supérieure	Partner	France
3	Karlsruhe Institute of Technology (KIT)	Partner	Germany
4	Weizmann Institute of Science	Partner	Israel