Gaze stabilization during head motion is a complex behavioral response that is highly dependent upon a functioning vestibular system. With vestibular loss, patients suffer gaze deficits that make it difficult to read, drive, or visually focus while moving throughout life. Remarkably, birds demonstrate complete spontaneous vestibular receptor regeneration following damage, unlike humans. In these animals, following regeneration, vestibular mediated gaze responses largely recover. However, the specific eye and head component responses that comprise gaze differ significantly following regeneration, suggesting that brain plasticity has re-wired the neural correlates that control gaze. In an effort to understand regenerative brain plasticity, the proposed project will examine the functional recovery of specific vestibular neural types that underly gaze control in pigeons.
In Specific Aim 1, neural recordings of vestibular afferent responses to motion will be obtained before a vestibular lesion and at four distinct time points during regeneration of the receptors. As motion signals are regenerated from the receptors, we will characterize the signals being restored and at what times.
Specific Aim 2 will examine the central vestibular neurons that specifically control the eye and head components of gaze behavior before, during, and after regeneration. Vestibular neurons that project to spinal cord or oculomotor centers will be characterized as motion signals are returning and the brain reorganizes gaze control circuits. Regeneration, gene therapy, and prosthetics are all developing into new technologies that will be used to treat vestibular loss in humans. Understanding how the brain adapts to these new motion signals will provide necessary insights to guide new treatment therapies and rehabilitation paradigms.
We will examine how the brain adapts to newly synthesized motion signals, through regeneration, to control the critical function of gaze stabilization. With vestibular loss, gaze stability is severely compromised throughout life, but newly developing technologies offer to replace lost receptor signals through regenerative or gene therapies. We believe these studies are significant, timely, and necessary in order to provide key insights into a paradigm shift in vestibular pathology treatment.
