It has become increasingly clear that synaptic function is served by complex arrays of neurotransmitters and neuromodulators. This situation is true as well in the synapses of the organs of the acousticolateralis system. The neuromodulators and transmitters of the semicircular canals for whose candidacy there is some experimental support include: acetylcholine (Ach), glutamate (Glu), adenosine (Ad), histamine (Hist), the tachykinins, especially substance P (S.P.), gamma-amino butyric acid (GABA) and calcitonin-gene-related peptide (CGRP). Where there remains some question of candidacy (i.e. Glu, Hist, S.P., GABA) the proposed research will examine the criteria remaining to be tested for the candidate. Where there is little doubt of the candidate's role (i.e. Ach, Ad) the proposed research will further characterize receptors and delineate the sites and mechanisms of action. The preparations to be used to carry out these objectives are: (1) the isolated saccule preparation of the frog; recording electrical activity of the hair cells and afferent dendrites. (2) Hair cells isolated from the crista ampullaris; recording currents and voltages by patch clamping techniques. (3) Cytochemical and immunocytochemical techniques at the light and electron microscopic level. These techniques are currently n hand. In addition the development of a preparation of afferent neurons with dendrites but without hair cells is in progress. This will be accomplished either by the use in vivo of agents toxic to the hair cells or by tissue culturing the afferent neurons. There is also a preparation of isolated whole labyrinth from which the spontaneous activity of afferent units of the saccular nerve will be recorded. By the use of this preparation the initial exploration of the pharmacology of the saccule will be accomplished. The vestibular periphery is the origin of pathological conditions such as vertigo and motion sickness which cause severe disruption of behavior and debilitation. An understanding of possible sites of pharmacologic attack such as neurotransmitters and modulators and their receptors should permit the design of drugs with action at the site of origin of these disorders, so that a rational base for vestibular therapeutics may be established as well as having relevance to function of hair cell systems in general.
| Guth, P S; Perin, P; Norris, C H et al. (1998) The vestibular hair cells: post-transductional signal processing. Prog Neurobiol 54:193-247 |
| Ricci, A; Norris, C; Guth, P (1991) Cyclic AMP modulates sensory-neural communication at the vestibular end organ. Brain Res 565:78-84 |
