BRAIN EAGER: Functional dynamics of whole brain activity, behavior, and development from birth to adulthood

Harvard University, Cambridge MA

Investigators

Abstract

From birth to adulthood, the brain and nervous system continuously expand and develop to keep up with the growing body. Neurons and connections must constantly be added or changed for any animal, including humans, to gain new behaviors or retain old ones. This project is to develop and apply technology to monitor brain and behavior from birth to adulthood of the roundworm C. elegans, an important and widely studied model for neuroscience. A controlled environment will be created where individual animals are born, roam freely, and grow to adulthood while a microscope continuously scans the activity patterns of every neuron in the worm's nervous system. Because of their rapid maturation (<2 days) and small nervous system (<302 neurons), the technology will be used to answer fundamental questions about the developing brain. For example, how do highly conserved behavioral patterns like forward and reverse movement emerge from a nervous system that adapts to a body that grows ten-fold from birth to adult? Coordinating the parallel development of brain, body, and behavior is a problem faced by all animals. The accessibility of C. elegans will yield the first comprehensive measurements of brain and behavior development in any animal. Bringing together developmental biology, neurophysiology, and neurotechnology will train young scientists who will work at the rich interface between the physical and life sciences. A system will be developed-- a motorized, rotating agar-coated ball-- upon which a nematode can freely move without interruption as it feeds, grows, molts through four larval stages, and becomes an adult. Throughout the nematode's life, the system will record the activity of the entire nervous system visualized throughout its optically transparent body using a confocal microscope that achieves video-rate volumetric recording. These experiments will provide unprecedented datasets that describe the behavioral life history of an individual animal in temporal correlation with whole brain activity patterns. Comparison of these rich datasets between wild-type animals and informative mutants will allow dissection of a wide range of interconnected and shared processes in neurodevelopment, regulation, learning, and memory. For example, understanding the developmental progression of the motor circuit will be achieved by obtaining circuit-wide measurements that describe how the 20-neuron motor circuit that drives the forward and backward movements of the 0.1-mm long juvenile worm is expanded into the 80-neuron motor circuit that drives the same movements of the 1-mm long adult. These studies will illuminate system-wide changes in the nervous system as it dynamically keeps up with animal growth.