Vestibular Influences on Head Direction Cell Activity

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DESCRIPTION (provided by applicant): Head direction cells (HDC) located in several regions of the brain, including the anterior dorsal nucleus of the thalamus, postsubiculum, and lateral mammillary nuclei, provide the neural substrate for the determination of directional heading. Although activity of HDC is influenced by various sensory signals and internally generated cues, lesion studies and some anatomical and physiological evidence suggest that vestibular inputs are critical for the maintenance of directional sensitivity of these cells. In addition, relatively direct pathways have been proposed that could relay vestibular signals to brain areas containing HDC. However, vestibular inputs must be transformed considerably in order to signal head direction, and it is uncertain whether the simple circuitry that has been postulated to mediate vestibular influences on HDC can accomplish this transformation of signals. One purpose of the proposed research is to establish whether a relatively direct pathway links the vestibular nuclei with brain areas containing HDC. Specific Aim 1 tests the hypothesis that injection of the retrograde transneuronal tracer pseudorabies virus into two areas containing HDC, the anterior dorsal nucleus of the thalamus and lateral mammillary nuclei, results in labeling of neurons in the vestibular nuclei within short survival times, suggesting that only a few synapses separate HDC from vestibular nucleus neurons. Furthermore, definitive physiological studies have not been conducted to determine whether HDC respond similarly during active head rotations and passive rotations of the animal's body that activate labyrinthine receptors. If labyrinthine signals contribute to the directional sensitivity of HDC as substantially as suggested by prior lesion studies, then these cells should respond to high-frequency passive horizontal rotations that powerfully activate semicircular canal afferents. Specific Aim 2 tests the hypothesis that HDC have similar responses to active head rotations in the horizontal plane and passive rotations imposed using a turntable, including rotations delivered in the dark such that the predominant sensory information available is from the labyrinth. These experiments will establish whether the vestibular system plays a direct and powerful role in determining directional heading, and should advance understanding of the neural underpinnings of navigation. This work may also provide insights into potential effects of peripheral and central vestibular lesions on spatial cognition in humans.