Maturation of locomotor control in zebrafish through development of spinal circuits

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The ability to move is essential to all organisms. Movements enable animals to survive and thrive. The spinal cord plays an essential role in the generation of most movements. Despite its central role in our movements, our understanding of how the spinal cord functions is lacking. A powerful approach to understanding the spinal cord is to study the maturation of motor circuits during development. Newborn animals start with a very rudimentary set of movements. As animals age, they acquire the ability to generate more complex and skillful movements that involve more refined coordination of muscles. While the control of motor activity matures, the spinal cord undergoes several changes that facilitate the acquisition of new maneuvers. New spinal neurons are born and integrated into existing spinal circuits. New connections with the brain and with other spinal neurons are made. The intrinsic properties of neurons also change during maturation. These changes enable the spinal cord to control more skillful movements. Identifying these alterations and how they lead to new movements leads to understanding the role of spinal neurons and the vital role of specific connections or firing patterns in producing new movements. The zebrafish is an ideal animal model to identify changes in the spinal cord that lead to new movements. Zebrafish embryos and larvae are capable of swimming movements shortly after inception. The transparency of developing zebrafish facilitates the study of the developing spinal cord. My research has previously shown how spinal circuits change during the transition from coiling to swimming in developing zebrafish. These findings led us to construct computational models based upon our experimental data and on a rapidly accumulating body of literature describing the growth of the neural population in the spinal cord and the assembly of new circuits. Simulations of our computational models were able to generate different coiling and swimming maneuvers in larval zebrafish. The analysis of our computational models revealed several testable predictions regarding 1) The role of firing behaviour in setting specific swim patterns, 2) The integration of new spinal neurons into spinal circuits, and 3) The establishment of new connections between spinal neurons. This research proposal investigates whether these three types of change enable the maturation of locomotor control in zebrafish. The sum of these objectives will provide a clearer understanding of how the spinal cord operates. The research program described will train a team of undergraduate and graduate students to gain sought-after experience with cutting-edge techniques in neurobiology, microscopy and molecular biology. Many types of spinal neurons are conserved amongst all vertebrates, including humans. Thus, our findings will give insights into how our spinal cords generate an entire repertoire of movements essential to our daily lives and that of most animal species.