Experience-dependent Cellular Plasticity Mechanisms

Brain activity is essential for the development and plasticity of neurons and circuits, however our understanding of the mechanisms by which activity generates functional circuits is incomplete. This lack of knowledge impedes our ability to take advantage of activity-dependent mechanisms to facilitate circuit

plasticity. Plasticity-inducing stimuli induce neuronal protein dynamics, including regulated increases and decreases in protein synthesis. We recently conducted a quantitative in vivo proteomic analysis which identified changes in newly synthesized proteins in the Xenopus tadpole visual system in response to

plasticity-inducing visual stimulation. We identified numerous candidate plasticity proteins (CPPs), including several that regulate protein synthesis, whereas others have diverse cellular and synaptic functions. Here we will probe the model that plasticity-inducing stimuli initiate a cascade of protein synthesis-dependent

events, beginning with de novo synthesis of upstream translational regulators and culminating in the regulated synthesis of diverse effector proteins, in visual experience dependent circuit plasticity in Xenopus, using proteomics, electrophysiology, in vivo structural and functional imaging, and behavioral assays.

Classical studies have revealed circuit-rewiring events in response to CNS damage. We have shown that local damage to the optic tectum impairs visual avoidance behavior in Xenopus and that treating injured animals with brief bouts of visual experience facilitates recovery of the injured circuit. To probe the flexibility

of experience-dependent plasticity mechanisms, we will test whether newly synthesized candidate plasticity proteins are required for the visual experience-dependent rehabilitation of the injured visuomotor circuit. Results of these experiments may identify novel mechanisms contributing to experience-dependent

plasticity in developing nervous systems.