Neural Mechanisms of Vestibular Function

PROJECT SUMMARY
We investigate an important function of the vestibular system, and its multisensory properties, in spatial
navigation, specifically head direction (HD) cells. HD cells encode directional heading like a compass and
these properties are generated through a ring attractor network that is defined by orienting landmarks and
updated using self-motion velocity cues. The goal of this renewal application is to establish the principles and
circuits linking vestibular signals to HD cells in the anterior thalamus, through three aims. In the first two aims
we will thoroughly test theory-driven hypotheses about the self-motion signal that updates the ring attractor.
We will disentangle two contributions to HD tuning strength: self-motion velocity input, and brain state, which
we hypothesize exerts a tonic modulatory role on the intrinsic properties of the attractor itself. We will show that
passive rotations are as effective in updating the HD attractor as active foraging, and will test model-driven
hypotheses about their multisensory properties. In Aim 3 we will genetically and optogenetically manipulate
large or discrete regions of the cerebellum while monitoring the activity of HD cells in anterodorsal and
laterodorsal thalamus. The hypothesized role of multisensory cerebellar signals is 2-fold: to help maintain
internal models about 1) rotation velocity, and 2) gravity. The former updates the firing and the latter defines
the 3D tuning of HD cells. Collectively, these experiments will provide a long-overdue, thorough and
quantitative understanding of the multisensory properties of one of the most important components of the
spatial navigation circuit. Our strength is an interdisciplinary approach based on a quantitative understanding of
both multisensory and computational neuroscience, which promises novel insights into the organization of the
spatial properties of HD cells and their links with the vestibular system.

Grant Number: 5R01DC004260-27
NIH Institute/Center: NIH
Principal Investigator: Dora Angelaki