This is a revised application (R01 03894-01A) that describes novel experiments using an in vitro brain preparation with attached temporal bones to study the initial vestibular processing of the vertebrate brainstem. The Principal Investigator initially developed these innovating techniques to study visual inputs to reflex paths that stabilize the retinal image. In this grant application, only head rotation responses will be studied in the vestibular nuclei. Whole-cell patch recordings of these responses will be examined before and after unilateral reversible lidocaine inactivation of the eighth nerve. Ipsilateral monosynaptic excitatory canal afferents converge onto neurons in the vestibular nucleus. A polysynaptic input is also thought to reach the same neurons from a contralateral canal with the corresponding axis of rotation. Vestibular nucleus neurons also display several response types during natural horizontal head rotation. Cells respond to motion to or away from the side of the recording, and their spike discharges can encode the head's velocity or acceleration. To elucidate the underlying neural circuitry of the vestibular nuclei, from the eighth nerve afferents and between the two nuclei, high-resolution patch recordings of individual synaptic events will be made as head rotation and electrical nerve stimulation evoke the excitatory and/or inhibitory pathways. Effects of synaptic drug applications will help identify the neurotransmitters involved in the monosynaptic and polysynaptic circuits. The membrane properties of the vestibular nucleus cells will be analyzed to see how they modify those synaptic inputs to yield the spike output of different vestibular response types. Redundant sensory input from both labyrinths is useful to improve vestibular sensitivity and to compensate for a unilateral loss. This project analyzes these bilateral inputs to gain an understanding of their role in the natural processing that results in a normal sense of balance or produces the feeling of vertigo during a pathological condition.
