The Bayesian brain hypothesis asserts that nervous systems in humans and animals transmit and process information as probability distributions, for which there is a growing body of psychophysical evidence. However, few investigations have endeavored to investigate Bayesian inference in early stages of sensory processing. Through this investigation we propose to implement such a test in primary afferent and secondary neurons of the inner ear vestibular system. We will explore afferent circuits of the horizontal semicircular canal, a model sensory system dedicated to coding and processing head kinematic state. The strength and novelty of our approach is that we advance a testable theory about how head state information may be represented by peripheral and central sensory neurons as spike measurement densities (i.e. SMDs) and spike posterior densities (i.e. SPDs) respectively. Furthermore, we submit the hypothesis that the central representation of the Bayesian posterior of head kinematic state is updated with new sense data (i.e. by primary afferent SMDs) via a neural analog of a particle filter. The particle filter provides the computational framework to tes whether the dynamic discharge of second-order vestibular neurons represent discrete loci of head kinematic state space. These experiments will be conducted in late-stage Xenopus larvae, from which the natural distribution of head kinematic states can be explicitly determined from videographic analysis of free-swimming animals. This natural distribution will be used to derive the dynamic prior within the particle filter model, and also serve as the basis of turntable stimul that can be used in the laboratories in the US and Germany to record evoked discharge from primary and second-order neurons, respectively. We will utilize the fictive swimming signals recordable from spinal ventral roots to modify the natural phase relationship between locomotor and head movement states by presenting head movement stimuli that conflict with the fictive motor efference copy. We hypothesize that such anomalous representations will lead to predictable errors in the central representation of the dynam-ic posterior through the collective SPDs, which would render strong support of a computational framework of Bayesian state estimation in spiking sensory neurons. Intellectual Merit: The intellectual merit of this proposal is harbored in the direct testing of Bayesian inference in nervous systems through direct neurophysiologic methods. Our goal is to test whether the Bayesian particle filter model extends well beyond just another way of describing spatial and temporal patterns of activity in vestibular neurons. Rather, we posit that i can predict and explain them, thereby advancing a compelling neurocomputational model of Bayesian inference using natural neuronal components. These experiments will also provide new insights into the role of dynamic heterogeneity among vestibular afferent neurons, which will undoubtedly lead to new research strategies that will ameliorate our understanding of vestibular sensory coding. Broader Impacts: The research encompasses broader impacts that include the integrative electrophysiologic and computational neuroscience training for individuals at the postdoctoral, graduate, and undergraduate levels. The postdoctoral scholar and graduate students will receive an intensely multidisciplinary experiences, with extraordinary opportunities for international collaboration with peers in the US, Germany, and New Zealand. They will receive rigorous exposure to the theoretical and computational aspects of this project. Undergraduate students will be recruited from across the nation as summer research fellows of the Minority Access to Research Careers program. These students, as well as other undergraduate associates participating during the course of the academic year, will have opportunities to engage in laboratory work addressing the multidisciplinary approaches involved in this project. We propose that this will have a significant impact in broadening their perspective of neuroscientific investigation. We have implemented a plan that will enable direct assessments of the undergraduate students'activities in the project, as well as assessments of the research program's impact upon their attitudes and outlook toward creative scientific endeavors and careers. Our goal is that the integrated approach and international friendships fostered by this project will positively impact their confidence and perspective concerning their own scientific creative capabilities.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Platt, Christopher
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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