Horizontal Semicircular Canal Afferents Research Articles

The effects of high energy radiation on the vestibular and immune function in rats (693.22)

The objective of the project is to study radiation effects on the vestibular and immune systems in rats. It is proposed that high energy radiation will compromise vestibular/balance system and immune function since nasopharyngeal cancer patients experience post‐irradiation vertigo and whole body radiation therapy causes immune suppression. However, the underlying mechanisms are not fully understood.Sprague‐Dawley rats were exposed to different doses of either unilateral cranial using 6 MeV electron beam (0 to 60Gy) or whole body using 18 MeV electron beam (0 to 10 Gy). For vestibular study, seven days post irradiation, single unit recording of vestibular afferent activity was performed. A total of 309 horizontal semicircular canal afferents’ responses to sinusoidal earth‐horizontal rotations (~1Hz) were analyzed. For immune function study, total RNAs were extracted from immune organs such as thymus and spleen. The genes involved in Stress and Toxicity PathwayFinder were examined using RT2 ProfilerTM PCR Array.Preliminary analysis shows that electron irradiation caused significant decreases in the gains of the irregular horizontal semicircular canal afferents. The gene expression profiles indicated significant changes in oxidative stress, DNA damage and repair as well as apoptosis related genes.In conclusion, these results indicate that irradiation exposure induces specific functional deficiency of the vestibular and immune system in rats.Grant Funding Source: Supported by NASA MSI EPSCoR (NNX12AK85A and NNX13AB31A), NIH R01DC012060 (HZ), NIH R01DC008585 (WZ)

Selective Activation of Vestibular Hair Cells by Infrared Light

Optical stimulation using pulsed infrared light is novel method with potential for selectively stimulating a small group of neurons. In present study, we show that infrared light can selectively activate vestibular hair cells and may offer a novel method to investigate biophysical mechanisms underlying the response. In experiments conducted in toadfish, O. tau, horizontal semicircular canal afferents showed a mix of inhibitory and excitatory responses evoked by infrared radiation. In a subset of afferents the background discharge rate decreased, while in other afferents the background discharge rate increased with infrared radiation. Excitatory vs. inhibitory afferent responses correlated with the dynamic adaptive properties of afferent responses observed during mechanical stimuli. Primary semicircular canal afferents in the toadfish are known to receive convergent inhibitory (GABA) and excitatory (glutamate) synaptic input from hair cells that ultimately shape the afferent discharge response. The present data indicate that afferents known to synapse on glutamatergic hair cells increase their discharge rate with incident infrared light, consistent with depolarization of hair cells and increased tonic release of glutamate. Acceleration-coding afferents which synapse on combinations of Glutamatergic and GABAergic hair cells were observed to reduce their discharge rate with infrared light, again indicating depolarization of hair cells but, in this case the inhibition was consistent with increased release of GABA. Repeated optical radiation elicited depolarization/repolarization of hair cells. Sensitive afferents were observed to phase-lock their discharge with the pulsed light stimulation. Since the entire epithelium was irradiated, this argues against simple kT thermodynamic modulation of hair cell channel kinetics. The results compel the hypotheses that infrared light stimulation increases the open probability of IR-sensitive ion channels and depolarizes hair cells due to the influx of cations. [Supported by NIH R01 DC06685 (Rabbitt, RD) and NIH grant 1R41DC008515-02 (Richter, CP)].

Latency and Initiation of the Human Vestibuloocular Reflex to Pulsed Galvanic Stimulation

Cathodal galvanic currents activate primary vestibular afferents, whereas anodal currents inhibit them. Pulsed galvanic vestibular stimulation (GVS) was used to determine the latency and initiation of the human vestibuloocular reflex. Three-dimensional galvanic vestibuloocular reflex (g-VOR) was recorded with binocular dual-search coils in response to a bilateral bipolar 100-ms rectangular pulse of current at 0.9 (near-threshold), 2.5, 5.0, 7.5, and 10.0 mA in 11 normal subjects. The g-VOR consisted of three components: conjugate torsional eye rotation away from cathode toward anode; vertical divergence (skew deviation) with hypertropia of the eye on the cathodal and hypotropia of the eye on the anodal sides; and conjugate horizontal eye rotation away from cathode toward anode. The g-VOR was repeatable across all subjects, its magnitude a linear function of the current intensity, its latency about 9.0 ms with GVS of >or=2.5 mA, and was not suppressed by visual fixation. At 10-mA stimulation, the g-VOR [x, y, z] on the cathodal side was [0.77 +/- 0.10, -0.05 +/- 0.05, -0.18 +/- 0.06 degrees ] (mean +/- 95% confidence intervals) and on the anodal side was [0.79 +/- 0.10, 0.16 +/- 0.05, -0.19 +/- 0.06 degrees ], with a vertical divergence of 0.20 degrees . Although the horizontal g-VOR could have arisen from activation of the horizontal semicircular canal afferents, the vertical-torsional g-VOR resembled the vestibuloocular reflex in response to roll-plane head rotation about an Earth-horizontal axis and might be a result of both vertical semicircular canal and otolith afferent activations. Pulsed GVS is a promising technique to investigate latency and initiation of the human vestibuloocular reflex because it does not require a large mechanical apparatus nor does it pose problems of head inertia or slippage.

Determinants of semicircular canal afferent response dynamics in fish.

Present results separate the relative contributions of semicircular canal biomechanics from hair cell/afferent biophysics in determining the amplitude and phase of afferent responses to sinusoidal motion of the head. Separation was achieved by combining electrical polarization of the endolymph with mechanical indentation of the canal limb to modulate the instantaneous firing rate of horizontal semicircular canal afferents. The electrical stimulus drives hair cell transduction currents via modulation of the Nernst-Planck potential, whereas the mechanical stimulus mimics head rotation and modulates the open probability of the transduction channels. Responses for electrical polarization therefore reflect post-transduction-current (PTC) mechanisms, and responses for mechanical stimulation include the additional influence of canal mechanics. Linear transfer functions defining individual afferent response dynamics were obtained for low levels of each stimuli and are reported in Bode form providing gain (spikes/s per micron or mV) and phase (deg re: peak stim) over the frequency range from 0.02 to 40 Hz. Combined results for electrical and mechanical stimuli distinguish the component of sensory signal processing carried out by canal mechanics from that carried out by the hair cell/afferent complexes. Individual afferents were categorized according to their response to the mechanical stimuli as low-gain velocity (LG), high-gain velocity (HG) or acceleration (A) sensitive, groups as originally defined by Boyle and Highstein to describe interafferent diversity present within the population. In contrast to the results for mechanical stimuli, all afferent groups exhibit nearly equal increases in gain and phase for increasing frequencies of electrical stimulation. Comparison of individual afferent responses for the two stimuli leads to the conclusion that the LG, HG, and A groups are distinguished primarily by diversity in the mechanical activation of associated hair cells and not by PTC mechanisms. Even though PTC processing does not contribute significantly to determining these groups, it is the primary determinant underlying high-frequency gain and phase enhancements observed in the population average. Comparison of mechanical and electrical responses also reveals the mechanical lower-corner responsible for phase enhancements and gain decreases in all afferents at low frequencies of mechanical stimulation (< 0.05 Hz). Results imply that LG afferents encode angular head velocity by canceling a phase lag and gain attenuation due to the mechanics with a phase lead and gain enhancement due to PTC mechanisms above approximately 0.2 Hz. In contrast, A group afferents encode angular head acceleration by combining high-frequency phase leads and gain enhancements present in both the mechanics and PTC mechanisms across the physiological frequency spectrum. HG afferents fall between these two extremes, and, other than the influence of the mechanical lower-corner, their response primarily reflects PTC processing.

Bilateral communication between vestibular labyrinths in pigeons

Extracellular action potentials from single horizontal semicircular canal primary afferent fibers were recorded in paralysed decerebrate pigeons during pulse mechanical stimulation of the contralateral horizontal semicircular canal. Clear responses to the contralateral membranous duct displacement stimuli were observed in 51% of the tested 158 horizontal semicircular canal afferents. Generally, three different types of responses were obtained in the primary afferent fibers including excitation, inhibition, and a few complex type neural activity profiles. Inhibitory responses were of larger amplitude and had longer time constants than did excitatory responses. The few complex type responses observed were characterized by an initial excitatory discharge followed by a longer duration decrease in the fiber's firing rate. The sensitivity to stimulation and type of response obtained for each afferent was significantly correlated with the fiber's coefficient of variation value. Regular firing afferents were less sensitive and exhibited primarily excitatory responses (71%) to contralateral canal stimulation. Irregular firing afferents were more sensitive and exhibited mostly inhibitory responses (84%). The present results demonstrate that a communication network for information exchange between the bilateral labyrinths exists in pigeons. The observed responses in primary afferent fibers to contralateral horizontal semicircular canal stimulation are proposed to be mediated by the vestibular efferent system, which could provide an anatomical pathway for information exchange from vestibular receptors on opposite sides of the head.

Activity of medial vestibulospinal tract cells during rotation and ocular movement in the alert squirrel monkey.

1. Chronic unit and eye movement recording and microstimulation techniques were used to study the discharge properties of identified medial vestibulospinal tract (MVST) cells in the alert squirrel monkey. MVST cells were antidromically activated from the ventromedial funiculus at C1 and responded to orthodromic stimulation of the ipsilateral VIIIth nerve (Vi) at mono- or disynaptic latencies. Cell discharges were examined during imposed sinusoidal yaw rotation to activate horizontal semicircular canal afferents and during voluntary ocular pursuit and fixation of visual targets with the head held stationary. 2. MVST cells represented 15% (22 of 147 cells) of the population of horizontal canal-related cells recorded in the vestibular nuclei. Twelve MVST cells were monosynaptically related to Vi; of these cells, 7 (58%) were characterized as ipsilateral eye and head velocity, having a discharge modulation related to the velocity of both ipsilaterally directed eye movement and yaw rotation, and 3 also had an ipsilateral eye position sensitivity. Most (8 of 10, 80%) MVST cells disynaptically related to Vi responded only to contralateral head velocity; the other 2 cells carried a combined contralateral head and ipsilateral eye movement signal. A pause or burst of discharge associated with fast or saccadic eye movements made in any direction was not present on the 22 MVST cells. 3. The MVST is an output pathway of the vestibular nuclei through which the labyrinth controls reflex head movements. The results show that MVST cells transmit the movement and position of eyes in orbit, with vestibular signals, to the cervical spinal cord and suggest that the MVST may play a dynamic role in voluntary gaze stabilization and eye/head tracking.

Changes in monkey horizontal semicircular canal afferent responses after spaceflight.

Extracellular responses from single horizontal semicircular canal afferents in two rhesus monkeys were studied after recovery from a 14-day biosatellite (COSMOS 2044) orbital spaceflight. On the 1st postflight day, the mean gain for 9 different horizontal canal afferents, tested using one or several different passive yaw rotation waveforms, was nearly twice that for 20 horizontal canal afferents similarly tested during preflight and postflight control studies. Adaptation of the afferent response to passive yaw rotation on the 1st postflight day was also greater. These results suggest that at least one component of the vestibular end organ (the semicircular canals) is transiently modified after exposure to 14 days of microgravity. It is unclear whether the changes are secondary to other effects of microgravity, such as calcium loss, or an adaptive response. If the response is adaptive, then this report is the first evidence that the response of the vestibular end organ may be modified (presumably by the central nervous system via efferent connections) after prolonged unusual vestibular stimulation. If this is the case, the sites of plasticity of vestibular responses may not be exclusively within central nervous system vestibular structures, as previously believed.

Morphological correlates of response dynamics and efferent stimulation in horizontal semicircular canal afferents of the toadfish, Opsanus tau

1. We used the intraaxonal labeling technique to study correlations between the terminal dendritic morphology of horizontal semicircular canal primary afferents and their response dynamics to sinusoidal head rotation and combined electrical stimulation of central efferent vestibular neurons. Thirty-eight canal afferents were identified by their sensitivity and phase of response to rotation between 0.1 and 1.0 Hz (+/- 10 degrees/s) and were subsequently labeled with horseradish peroxidase or biocytin. The afferent's dendritic field and synaptic specializations in the neuroepithelium of the crista were examined under light microscopy. 2. Rate and regularity of background discharge of the afferent were not correlated with its axon diameter or relative location of its dendritic field in the crista. 3. Response sensitivity of the afferent to rotation was correlated both with the relative location of its dendritic field in the crista and with the number of terminal endings it possesses. Afferents having low sensitivities, slow dynamics, and few terminal endings supply the peripheral portions of the crista; afferents with higher sensitivities, faster dynamics, and greater number of terminal endings supply the more central portions. It is suggested that the differences in sensitivity among the afferents reflect principally the variations in both the cupular dynamics along the crista and the number of possible hair cell contact sites in the neuroepithelium. 4. Response phase of the afferent was correlated only with the extent of its dendritic processes along the transverse axis of the crista. Afferents having transversely oriented dendritic fields had less phase lags relative to acceleration than did those having a more longitudinally oriented dendritic field. 5. Efferent stimulation produced a change in both the afferent's discharge rate and its response sensitivity to rotation. Afferents discharge rate and its response sensitivity to rotation. Afferents having a centrally located dendritic field and acceleration afferents, defined by their response to rotation, were the most affected by efferent stimulation. These results suggest that efferent innervation is either directed toward, or most efficacious in, the central regions of the crista and that it may select specific hair cell-afferent complexes.

Responses of Horizontal Semicircular Canal Afferents to Rotatory and Mechanical Stimulation.

Responses of Horizontal Semicircular Canal Afferents to Rotatory and Mechanical Stimulation.

Efferent vestibular system in the toadfish: action upon horizontal semicircular canal afferents

The influence of the efferent vestibular system (EVS) upon the background discharge and response dynamics of horizontal semicircular canal afferents was examined in the toadfish. In one set of experiments the EVS was activated using a behavioral paradigm; in the second, electrical shocks were applied to the efferent vestibular nucleus in the brain stem. The afferent's background discharge and responses to rotation were recorded before and during efferent stimulation. Both EVS activation paradigms gave qualitatively similar results: a facilitation of the afferent's rate, while the animal was at rest or in motion, and a reduction in response sensitivity. Afferents were not affected uniformly: low-gain, velocity-sensitive afferents were weakly influenced, while high-gain and acceleration afferents having low rates were the most excited. The afferents' phase of response was unmodified by electrical EVS stimulation. In many afferents a prominent form of response nonlinearity is discharge silencing over large portions of the stimulus cycle. Efferent-evoked rate increase was often sufficient to produce a full-cycle bidirectional response. Caloric facilitation of afferent rate confirmed that the EVS-induced sensitivity decrease was rate independent. These results show a dual action of the efferent system: (1) facilitating the afferent's rate and (2) reducing its sensitivity to adequate stimulation that may be correlated with the dual EVS synaptic innervation of the labyrinth, namely postsynaptic efferent-afferent synapses and presynaptic efferent-hair cell synapses.

Resting discharge and response dynamics of horizontal semicircular canal afferents of the toadfish, Opsanus tau

The response dynamics of 66 primary afferents of the horizontal semicircular canal were studied in the toadfish using sinusoidal, rotational stimuli from 0.001-10 Hz at amplitudes of 5-100 degrees/sec. Twelve afferents were also tested to constant velocity trapezoids. Responses to sinusoids were used to classify afferents into 3 broad groups: (1) low-gain afferents that maintain a relatively linear response re: stimulus velocity across most of the frequency and amplitude spectra tested; (2) high-gain afferents that have a velocity sensitivity but also show a high-frequency gain enhancement and phase advance; and (3) so-called acceleration afferents that have a response more in phase with stimulus acceleration than velocity across the tested bandwidth. The afferent's background discharge was examined in relation to its rotational response. Low-gain afferents have regular spacing of interspike intervals. High-gain and acceleration afferents have a widely variable discharge regularity that is apparently unrelated to their rotational responses. Input/output transfer models were fit to the response data to describe the low- and high-pass filtering properties of the 3 afferent groups.

Dynamic properties of vestibular reflexes in the decerebrate cat.

Vestibulocollic (VCR) and vestibulo-ocular (VOR) reflexes were studied during angular rotation in the horizontal plane in precollicular decerebrate cats. Angular position was modulated by sinusoids or sums of sinusoids with frequencies ranging from 0.05 to 5 Hz. Reflex motor output was measured by recording electromyographic (EMG) activity of the lateral rectus and dorsal neck muscles and discharge of abducens motoneurons. Measured with respect to input angular acceleration VCR motor output displayed a second order lag at low frequencies, bringing mean EMG phase (-136 degrees) and gain slope (-35 dB/decade) close to those of an angular position signal at 0.2 Hz. At higher frequencies the lag was counteracted by a second order lead bringing mean phase (-52 degrees) and gain slope (-5.6 dB/decade) back close to those of an angular acceleration signal at 3 Hz. By contrast, mean phase (-113 degrees to -105 degrees) and gain slope (-21 to -28 dB/decade) of the VOR motor output remained close to those of an angular velocity signal across the entire frequency range. The data suggest that neural pathways producing the VCR receive selective input from "irregular type" horizontal semicircular canal afferents which provide one lag and one lead in the overall transfer function while the other lag and lead are produced by central pathways. Transection of the medial longitudinal fasciculus (MLF), which eliminates all of the most direct (three neuron) arcs of the horizontal VCR, did not cause any detectable change in the horizontal VCR at either low or high frequencies. Reductions in overall gain occurred in some cases but these could be attributed to damage to axons outside the MLF. Less direct pathways, probably including vestibuloreticulospinal pathways, are thus able to produce both the low-frequency, phase-lagging and high-frequency, phase-leading components of the horizontal VCR.

Behavior of horizontal semicircular canal afferents in alert monkey during vestibular and optokinetic stimulation.

The behavior of single vestibular nerve fibers from the lateral semicircular canal was recorded during sinusoidal oscillations of the head, during optokinetic stimulation with the head stationary, and during spontaneous oculomotor behavior in the alert monkey. The response of similar fibers to adequate vestibular stimulation was also studied in some of the animals under deeply anesthetized conditions. In the alert animals all units were spontaneously active and their discharge was modulated only by adequate vestibular stimulation. Ipsilateral horizontal rotations of the head were excitatory for all units. No modification of this basic vestibular response by visual stimulation including full-field striped drum rotation was observed. Furthermore no correlation of unit activity with oculomotor function including voluntary saccadic and pursuit eye movements was found in any of the units. The regularity of spontaneous discharge was the most consistent characteristic that differentiated the unit response into types. Most units were very regular in discharge, but a few were very irregular. The averaging of unit discharge over several cycles of oscillatory head rotation showed that the irregular type units were also consistently modulated by adequate vestibular stimulation. Both regular and irregular type units were found in the anesthetized animals. Unimodal distributions of the quantitative values for unit resting discharge rate, sensitivity, and phase relationship were found. The distributions for these three parameters were similar in the units recorded in the anesthetized animals. Thus at least these characteristics of semicircular canal response seem not to be affected by the vestibular efferent system which should be altered or eliminated in the case of the anesthetized animals.