It has been over 60 years since peripheral efferent vestibular terminals were first identified in mammals, and yet the function of the efferent vestibular system remains obscure. One reason for the lack of progress may be due to our deficient understanding of the peripheral efferent synapse. Although vestibular efferent terminals were identified as cholinergic less than a decade after their anatomical characterization, the cellular mechanisms that underlie the properties of these synapses have had to be inferred. In this review we examine how recent mammalian studies have begun to reveal both nicotinic and muscarinic effects at these terminals and therefore provide a context for fast and slow responses observed in classic electrophysiological studies of the mammalian efferent vestibular system, nearly 40 years ago. Although incomplete, these new results together with those of recent behavioral studies are helping to unravel the mysterious and perplexing action of the efferent vestibular system. Armed with this information, we may finally appreciate the behavioral framework in which the efferent vestibular system operates.

Ototoxicity is a major cause of the loss of hearing and balance in humans. Ototoxic compounds include pharmaceuticals such as aminoglycoside antibiotics, anti-malarial drugs, loop diuretics and chemotherapeutic platinum agents, and industrial chemicals including several solvents and nitriles. Human and rodent data indicate that the main target of toxicity is hair cells (HCs), which are the mechanosensory cells responsible for sensory transduction in both the auditory and the vestibular system. Nevertheless, the compounds may also affect the auditory and vestibular ganglion neurons. Exposure to ototoxic compounds has been found to cause HC apoptosis, HC necrosis, and damage to the afferent terminals, of differing severity depending on the ototoxicity model. One major pathway frequently involved in HC apoptosis is the c-jun N-terminal kinase (JNK) signaling pathway activated by reactive oxygen species, but other apoptotic pathways can also play a role in ototoxicity. Moreover, little is known about the effects of chronic low-dose exposure. In rodent vestibular epithelia, extrusion of live HCs from the sensory epithelium may be the predominant form of cell demise during chronic ototoxicity. In addition, greater involvement of the afferent terminals may occur, particularly the calyx units contacting type I vestibular HCs. As glutamate is the neurotransmitter in this synapse, excitotoxic phenomena may participate in afferent and ganglion neuron damage. Better knowledge of the events that take place in chronic ototoxicity is of great interest, as it will increase understanding of the sensory loss associated with chronic exposure and aging.

The vestibular labyrinth of nearly every vertebrate class receives a prominent efferent innervation that originates in the brainstem and ends as bouton terminals on vestibular hair cells and afferents in each end organ. Although the functional significance of this centrifugal pathway is not well understood, it is clear that efferent neurons, when electrically stimulated under experimental conditions, profoundly impact vestibular afferent discharge. Effects range from chiefly excitation in fish and mammalian vestibular afferents to a more heterogeneous mixture of inhibition and/or excitation in amphibians, reptiles, and birds. What accounts for these diverse response properties? Recent cellular and pharmacological characterization of efferent synaptic mechanisms in turtle offers some insight. In the turtle posterior crista, vestibular efferent neurons are predominantly cholinergic and the effects of efferent stimulation on vestibular afferent discharge can be ascribed to three distinct signaling pathways: (1) Hyperpolarization of type II hair cells mediated by α9/α10-nAChRs and SK-potassium channels; (2) Depolarization of bouton and calyx afferents via α4β2*-containing nAChRs; and (3) A slow excitation of calyx afferents attributed to muscarinic AChRs. In this review, we discuss the evidence for these pathways in turtle and speculate on their role in mammalian vestibular efferent actions where synaptic mechanisms are largely unknown.

The functional significance of the ciliary interconnections and cupula has been reviewed. The ciliary interconnecting systems are divided into 2 types, i.e. side links and tip links. The side links acts to maintain the regular distance between the cilia thereby keeping the geometrical arrangement of the entire sensory hair bundle intact as well as to prevent close contact between neighbouring cilia. The tip links, stretching upwards from the tips of the shorter stereocilia to their taller neighbouring shafts, are actually involved in mechanoelectrical transduction. The cupula is composed of the cupula and subcupular meshwork. The subcupular meshwork consists of long branching filaments cross-bridged to one another. The cupula would function as a rigid plate and equally distribute the shear force of the cupula to all the ciliary bundles. The subcupular meshwork may play a role in the transmission of the shear strain force of the cupula to the ciliary bundle and may also exert an additional damping effect in order to prevent unwanted vibrations.

暂无摘要。