Sensorimotor processing, decision making, and internal states: towards a realistic multiscale circuit model of the larval zebrafish brain

Project: Research project

Project Details

Description

All behaviors rely on the activity of pools of motor neurons and the skeletal muscle fibers they innervate. In vertebrates, the neural circuits responsible for coordinating motor pools during numerous behaviors, including locomotion, reside in the brainstem and spinal cord. Work in my lab has been focused on mapping the connectivity of excitatory and inhibitory circuits responsible for vertebrate locomotor control. To do so, we use a combination of imaging, molecular and electrophysiological techniques in larval zebrafish. Only a few days after egg fertilization, larval zebrafish already exhibit a behavioral repertoire that allows them to eat and avoid being eaten. Central to this goal is the ability of zebrafish to navigate in three-dimensions, whether exploring new environments or escaping harmful ones. To do so, the larvae swim much like their parents – forward propulsion is achieved by an alternating wave of body curvature that passes from head to tail. What is still not clear, however, is how coordination of activity along and across the body is integrated with command signals that would allow for the differential recruitment of motor pools required to alter the trajectory of swimming.
This is the issue we are hoping to address by participating in Project 3 of this application. To put it bluntly, we are past the point where intuition provides a satisfactory explanation of the data – the time has come to build computational models to begin to interpret the patterns we are observing. Our contribution to the project will be to develop models of brainstem and spinal circuits that could account for the differential coordination of tail movements that serve as the fundamental basis for executing many, if not all, of the behaviors outlined in the proposal. We anticipate a good deal of back-and-forth between experimentalists and theorists. Our models are (and will be) based on pair-wise electrophysiological recordings from specific, identifiable populations of neurons labeled with optical reporters, sensors or actuators in the brainstem and spinal cord of transgenic lines of fish. We will be able to collect critical biophysical information (e.g., ionic conductances, synaptic currents, conduction velocities) that not only constrain but also inform computational models. By adding our weight to the considerable expertise collected in this proposal, we hope to provide one of the most comprehensive descriptions of how neural circuits are organized to generate behavior.
StatusActive
Effective start/end date9/25/178/31/22

Funding

  • Harvard University (138078-5105175//5U19NS104653-03)
  • National Institute of Neurological Disorders and Stroke (138078-5105175//5U19NS104653-03)

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