Reticulospinal Execution of Innate Decision-Making

Northwestern University, Evanston IL

Investigators

Abstract

The decision to approach or avoid is a fundamental aspect of animal behavior. How this decision is made by networks of motor neurons that are located in the brainstem and spinal cord, and which trigger muscle cell contraction, is still unclear. This project will investigate the neural and mechanical basis of innate decision-making in vertebrates. Studies will be carried out using zebrafish larvae because they undergo a change in their innate decision-making ability during the first few days after hatching. Immediately after hatching, zebrafish larvae have the ability to generate escape behavior in response to threats. Three days later, they add the ability to not only avoid, but to approach and attack small objects. The goal of this project will be to determine how the neural circuitry supporting the decision to escape or approach visually detected objects is organized during development. Graduate students will be trained in the use of cutting-edge electrophysiological, imaging, computational and behavioral techniques uniquely applied in the zebrafish model system. In addition, an outreach program will be designed and implemented to introduce local high school students to basic neurobiological concepts addressed in this project. The program will involve intuitive and interactive experiments using simple robots with circuits that can be modified to create the approach or avoidance behaviors observed in fish. The investigators will pursue several hypotheses regarding the development of approach and avoidance behaviors in larval zebrafish. Aim 1 will use high-speed videography and automated body tracking to evaluate the hypothesis that the circuitry for approach is not in place until later on in development. The expectation is that only the older larvae will be able to generate kinematically-distinct responses to attractive visual stimuli. Aim 2 will distinguish between two leading possibilities for how reticular circuitry mediates approach and avoidance, either via the addition of new components or the modification of pre-existing ones. In vivo dye labeling combined with functional calcium imaging approaches will assess changes in the morphologies and responses to visual stimuli of readily identifiable reticular neurons during development. In vivo patch clamp recordings will also be used to confirm outputs to spinal circuitry. Aim 3 will examine the likelihood that newly developed approach circuitry in the spinal cord is either overpowered or shut off by reticulospinal drive during avoidance maneuvers. The predictable read-outs of either scenario will be assessed using electrophysiological recordings of motor output, advanced computational fluids and body modeling, and targeted laser ablations followed by kinematic analysis.