Dissecting the mechanisms of neural circuit maturation that underpin behavioral development using zebrafish

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All animals are born with a set of reflexive behaviours that ensure their immediate survival. As animals mature, they become capable of increasingly sophisticated behaviours. Addressing the underlying mechanisms of circuit maturation in the brain is essential to understanding how neural circuits develop, are functionally organized, and operate. Despite tremendous progress in our knowledge about early brain formation and the function of mature brains, very little is known about the relationship between brain maturation and behavioural development. Gaining insights into this relationship has been difficult due to the necessity to study both the formation and function of increasingly complex emerging circuits as they dynamically integrate with existing motor control circuitry. This research is especially challenging in mammalian models that present formidable technical hurdles due to the scale and complexity of the brain. My laboratory tackles this challenge using larval zebrafish, a powerful vertebrate model system used for studying both the formation and function of the brain. The larval zebrafish provides excellent genetic and optical access, and develops a rich set of behaviours within a few days after birth. Furthermore, its brain is vastly more compact than mammalian models despite having a well-conserved vertebrate brain architecture. Thus, this organism makes it possible to genetically label specific sets of developing neurons and optically monitor how they become integrated into circuits and ultimately contribute to behaviour. Using this strategy, my research has previously revealed fundamental brain organization principles that underlie the expansion of motor outputs observed during early behavioural development. In this proposal, we aim to reveal circuit mechanisms that facilitate an animal's ability to produce flexible movement sequences at later stages of behavioural development. Specifically, we will perform in-depth analyses of the neuronal circuits involved in sequential locomotor behaviour using cutting-edge optical and genetic techniques. Through this research, we aim to reveal the brain mechanisms that enable integration and flexible recruitment of new circuit components without compromising existing components. This research has the potential to provide insights that will guide the development of artificial intelligence and robotics technologies that enable interaction with the external world through flexible sequences of actions.