Cholinergic Modulation of Membrane Properties of Calyx Terminals in the Vestibular Periphery.

Vestibular nerve afferents are divided into regular and irregular groups based on the variability of interspike intervals in their resting discharge. Most afferents receive inputs from bouton terminals that contact type II hair cells as well as from calyx terminals that cover the basolateral walls of type I hair cells. Calyces have an abundance of different subtypes of KCNQ (Kv7) potassium channels and muscarinic acetylcholine receptors (mAChRs) and receive cholinergic efferent inputs from neurons in the brainstem.

Activation of GABA receptors results in excitatory modulation of calyx terminals in rat semicircular canal cristae.

Previous studies have found GABA in vestibular end organs. However, existence of GABA receptors or possible GABAergic effects on vestibular nerve afferents has not been investigated. The current study was conducted to determine whether activation of GABA receptors affects calyx afferent terminals in the central region of the cristae of semicircular canals.

Efferent synaptic transmission at the vestibular type II hair cell synapse.

In the vestibular peripheral organs, type I and type II hair cells (HCs) transmit incoming signals via glutamatergic quantal transmission onto afferent nerve fibers. Additionally, type I HCs transmit via "non-quantal" transmission to calyx afferent fibers, by accumulation of glutamate and potassium in the synaptic cleft. Vestibular efferent inputs originating in the brainstem contact type II HCs and vestibular afferents.

A novel intracochlear injection method for rapid drug delivery to vestibular end organs.

Background: Injection into the inner ear through the round window (RW) or a cochleostomy is a reliable method for delivering drugs or viruses to the cochlea. This method has been less effective for fast deliveries to vestibular end organs.

New Method: We describe a novel approach for rapid delivery of drugs to the vestibular end organ via the oval window (OW) and scala vestibuli in 1-3 month old C57BL/6 mice.

Using Unidirectional Rotations to Improve Vestibular System Asymmetry in Patients with Vestibular Dysfunction.

The vestibular system provides information about head movement and mediates reflexes that contribute to balance control and gaze stabilization during daily activities. Vestibular sensors are located in the inner ear on both sides of the head and project to the vestibular nuclei in the brainstem. Vestibular dysfunction is often due to an asymmetry between input from the two sides.

Efferent Inputs Are Required for Normal Function of Vestibular Nerve Afferents.

A group of vestibular afferent nerve fibers with irregular-firing resting discharges are thought to play a prominent role in responses to fast head movements and vestibular plasticity. We show that, in C57BL/6 mice (either sex, 4-5 weeks old), normal activity in the efferent vestibular pathway is required for function of these irregular afferents. Thermal inhibition of efferent fibers results in a profound inhibition of irregular afferents' resting discharges, rendering them inadequate for signaling head movements.

Rebalancing the Vestibular System by Unidirectional Rotations in Patients With Chronic Vestibular Dysfunction.

Vestibular dysfunction is a common disorder that results in debilitating symptoms. Even after full compensation, the vestibulo-ocular reflex (VOR) could be further improved by using rehabilitation exercises and visual-vestibular adaptation. We hypothesized that in patients with asymmetric vestibular function, the system could be rebalanced by unidirectional rotations toward the weaker side (i.

Glutamatergic signaling at the vestibular hair cell calyx synapse.

In the vestibular periphery a unique postsynaptic terminal, the calyx, completely covers the basolateral walls of type I hair cells and receives input from multiple ribbon synapses. To date, the functional role of this specialized synapse remains elusive. There is limited data supporting glutamatergic transmission, K(+) or H(+) accumulation in the synaptic cleft as mechanisms of transmission.

Neuronal detection thresholds during vestibular compensation: contributions of response variability and sensory substitution.

The vestibular system is responsible for processing self-motion, allowing normal subjects to discriminate the direction of rotational movements as slow as 1-2 deg s(-1). After unilateral vestibular injury patients' direction-discrimination thresholds worsen to ∼20 deg s(-1), and despite some improvement thresholds remain substantially elevated following compensation. To date, however, the underlying neural mechanisms of this recovery have not been addressed.

Neural correlates of sensory substitution in vestibular pathways following complete vestibular loss.

Sensory substitution is the term typically used in reference to sensory prosthetic devices designed to replace input from one defective modality with input from another modality. Such devices allow an alternative encoding of sensory information that is no longer directly provided by the defective modality in a purposeful and goal-directed manner. The behavioral recovery that follows complete vestibular loss is impressive and has long been thought to take advantage of a natural form of sensory substitution in which head motion information is no longer provided by vestibular inputs, but instead by extravestibular inputs such as proprioceptive and motor efference copy signals.

Multimodal integration after unilateral labyrinthine lesion: single vestibular nuclei neuron responses and implications for postural compensation.

Plasticity in neuronal responses is necessary for compensation following brain lesions and adaptation to new conditions and motor learning. In a previous study, we showed that compensatory changes in the vestibuloocular reflex (VOR) following unilateral vestibular loss were characterized by dynamic reweighting of inputs from vestibular and extravestibular modalities at the level of single neurons that constitute the first central stage of VOR signal processing. Here, we studied another class of neurons, i.

Neural correlates of motor learning in the vestibulo-ocular reflex: dynamic regulation of multimodal integration in the macaque vestibular system.

Motor learning is required for the reacquisition of skills that have been compromised as a result of brain lesion or disease, as well as for the acquisition of new skills. Behaviors with well characterized anatomy and physiology are required to yield significant insight into changes that occur in the brain during motor learning. The vestibulo-ocular reflex (VOR) is well suited to establish connections between neurons, neural circuits, and motor performance during learning.

Effects of canal plugging on the vestibuloocular reflex and vestibular nerve discharge during passive and active head rotations.

Mechanical occlusion (plugging) of the slender ducts of semicircular canals has been used in the clinic as well as in basic vestibular research. Here, we investigated the effect of canal plugging in two macaque monkeys on the horizontal vestibuloocular reflex (VOR) and the responses of vestibular-nerve afferents during passive head rotations. Afferent responses to active head movements were also studied.

How actions alter sensory processing: reafference in the vestibular system.

Our vestibular organs are simultaneously activated by our own actions as well as by stimulation from the external world. The ability to distinguish sensory inputs that are a consequence of our own actions (vestibular reafference) from those that result from changes in the external world (vestibular exafference) is essential for perceptual stability and accurate motor control. Recent work in our laboratory has focused on understanding how the brain distinguishes between vestibular reafference and exafference.

Different neural strategies for multimodal integration: comparison of two macaque monkey species.

The integration of neck proprioceptive and vestibular inputs underlies the generation of accurate postural and motor control. Recent studies have shown that central mechanisms underlying the integration of these sensory inputs differ across species. Notably, in rhesus monkey (Macaca mulata), an Old World monkey, neurons in the vestibular nuclei are insensitive to passive stimulation of neck proprioceptors.

Neural substrates underlying vestibular compensation: contribution of peripheral versus central processing.

The vestibulo-ocular reflex (VOR), which functions to stabilize gaze and ensure clear vision during everyday activities, shows impressive adaptation in response to environmental requirements. In particular, the VOR exhibits remarkable recovery following the loss of unilateral labyrinthine input as a result of injury or disease. The relative simplicity of the pathways that mediate the VOR, make it an excellent model system for understanding the changes (learning) that occur in the brain following peripheral vestibular loss to yield adaptive changes.

Efferent-mediated responses in vestibular nerve afferents of the alert macaque.

The peripheral vestibular organs have long been known to receive a bilateral efferent innervation from the brain stem. However, the functional role of the efferent vestibular system has remained elusive. In this study, we investigated efferent-mediated responses in vestibular afferents of alert behaving primates (macaque monkey).

Response of vestibular nerve afferents innervating utricle and saccule during passive and active translations.

The distinction between sensory inputs that are a consequence of our own actions from those that result from changes in the external world is essential for perceptual stability and accurate motor control. In this study, we investigated whether linear translations are encoded similarly during active and passive translations by the otolith system. Vestibular nerve afferents innervating the saccule or utricle were recorded in alert macaques.

Neural variability, detection thresholds, and information transmission in the vestibular system.

A fundamental issue in neural coding is the role of spike timing variation in information transmission of sensory stimuli. Vestibular afferents are particularly well suited to study this issue because they are classified as either regular or irregular based on resting discharge variability as well as morphology. Here, we compared the responses of each afferent class to sinusoidal and random head rotations using both information theoretic and gain measures.

Response of vestibular-nerve afferents to active and passive rotations under normal conditions and after unilateral labyrinthectomy.

We investigated the possible contribution of signals carried by vestibular-nerve afferents to long-term processes of vestibular compensation after unilateral labyrinthectomy. Semicircular canal afferents were recorded from the contralesional nerve in three macaque monkeys before [horizontal (HC) = 67, anterior (AC) = 66, posterior (PC) = 50] and 1-12 mo after (HC = 192, AC = 86, PC = 57) lesion. Vestibular responses were evaluated using passive sinusoidal rotations with frequencies of 0.

Dynamics of the horizontal vestibuloocular reflex after unilateral labyrinthectomy: response to high frequency, high acceleration, and high velocity rotations.

Loss of vestibular information from one labyrinth results in a marked asymmetry in the horizontal vestibuloocular reflex (VOR). The results of prior studies suggest that long-term deficits in VOR are more severe in response to rapid impulses than to sinusoidal head movements. The goal of the present study was to investigate the VOR following unilateral labyrinthectomy in response to different stimuli covering the full range of physiologically relevant head movements in macaque monkeys.