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. Information theoretic measures demonstrated that regular afferents transmitted, on average, two times more information than irregular afferents, despite having significantly lower gains. Moreover, consistent with information theoretic measures, regular afferents had angular velocity detection thresholds that were 50% lower than those of irregular afferents (ϳ4 vs 8°/s). Finally, to quantify the information carried by spike times, we added spike-timing jitter to the spike trains of both regular and irregular afferents. Our results showed that this significantly reduced information transmitted by regular afferents whereas it had little effect on irregular afferents. Thus, information is carried in the spike times of regular but not irregular afferents. Using a simple leaky integrate and fire model with a dynamic threshold, we show that differential levels of intrinsic noise can explain differences in the resting discharge, the responses to sensory stimuli, as well as the information carried by action potential timings of each afferent class. Our experimental and modeling results provide new insights as to how neural variability influences the strategy used by two different classes of sensory neurons to encode behaviorally relevant stimuli.

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 0.5-15 Hz (20-80 degrees /s) and fast whole-body rotations reaching velocities of 500 degrees /s. Sensitivities to nonvestibular inputs were tested by: 1) comparing responses during active and passive head movements, 2) rotating the body with the head held stationary to activate neck proprioceptors, and 3) encouraging head-restrained animals to attempt to make head movements that resulted in the production of neck torques of < or =2 Nm. Mean resting discharge rate before and after the lesion did not differ for the regular, D (dimorphic)-irregular, or C (calyx)-irregular afferents. In response to passive rotations, afferents showed no change in sensitivity and phase, inhibitory cutoff, and excitatory saturation after unilateral labyrinthectomy. Moreover, head sensitivities were similar during voluntary and passive head rotations and responses were not altered by neck proprioceptive or efference copy signals before or after the lesion. The only significant change was an increase in the proportion of C-irregular units postlesion, accompanied by a decrease in the proportion of regular afferents. Taken together, our findings show that changes in response properties of the vestibular afferent population are not likely to play a major role in the long-term changes associated with compensation after unilateral labyrinthectomy.

No abstract

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 ϩ or H ϩ accumulation in the synaptic cleft as mechanisms of transmission. Here the role of glutamatergic transmission at the calyx synapse is investigated. Whole-cell patch-clamp recordings from calyx endings were performed in an in vitro whole-tissue preparation of the rat vestibular crista, the sensory organ of the semicircular canals that sense head rotation. AMPA-mediated EPSCs showed an unusually wide range of decay time constants, from Ͻ5 to Ͼ500 ms. Decay time constants of EPSCs increased (or decreased) in the presence of a glutamate transporter blocker (or a competitive glutamate receptor blocker), suggesting a role for glutamate accumulation and spillover in synaptic transmission. Glutamate accumulation caused slow depolarizations of the postsynaptic membrane potentials, and thereby substantially increased calyx firing rates. Finally, antibody labelings showed that a high percentage of presynaptic ribbon release sites and postsynaptic glutamate receptors were not juxtaposed, favoring a role for spillover. These findings suggest a prominent role for glutamate spillover in integration of inputs and synaptic transmission in the vestibular periphery. We propose that similar to other brain areas, such as the cerebellum and hippocampus, glutamate spillover may play a role in gain control of calyx afferents and contribute to their high-pass properties.

Sadeghi SG, Minor LB, Cullen KE. Multimodal integration after unilateral labyrinthine lesion: single vestibular nuclei neuron responses and implications for postural compensation. J Neurophysiol 105: 661-673, 2011. First published December 8, 2010 doi:10.1152/jn.00788.2010. 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.e., the vestibular-only neurons, in the vestibular nuclei that mediate vestibulospinal reflexes and provide information for higher brain areas. We investigated changes in the relative contribution of vestibular, neck proprioceptive, and efference copy signals in the response of these neurons during compensation after contralateral vestibular loss in Macaca mulata monkeys. We show that the time course of recovery of vestibular sensitivity of neurons corresponds with that of lower extremity muscle and tendon reflexes reported in previous studies. More important, we found that information from neck proprioceptors, which did not influence neuronal responses before the lesion, were unmasked after lesion. Such inputs influenced the early stages of the compensation process evidenced by faster and more substantial recovery of the resting discharge in proprioceptive-sensitive neurons. Interestingly, unlike our previous study of VOR interneurons, the improvement in the sensitivity of the two groups of neurons did not show any difference in the early or late stages after lesion. Finally, neuronal responses during active head movements were not different before and after lesion and were attenuated relative to passive movements over the course of recovery, similar to that observed in control conditions. Comparison of compensatory changes observed in the vestibuloocular and vestibulospinal pathways provides evidence for similarities and differences between the two classes of neurons that mediate these pathways at the functional and cellular levels.

Jamali M, Sadeghi SG, Cullen KE. Response of vestibular-nerve afferents innervating utricle and saccule during passive and active translations. J Neurophysiol 101: 141-149, 2009. First published October 29, 2008 doi:10.1152/jn.91066.2008. 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. Single unit responses were compared during passive whole body, passive head-on-body, and active head-on-body translations (vertical, fore-aft, or lateral) to assess the relative influence of neck proprioceptive and efference copy-related signals on translational coding. The response dynamics of utricular and saccular afferents were comparable and similarly encoded head translation during passive whole body versus head-on-body translations. Furthermore, when monkeys produced active head-on-body translations with comparable dynamics, the responses of both regular and irregular afferents remained comparable to those recorded during passive movements. Our findings refute the proposal that neck proprioceptive and/or efference copy inputs coded by the efferent system function to modulate the responses of the otolith afferents during active movements. We conclude that the vestibular periphery provides faithful information about linear movements of the head in the space coordinates, regardless of whether they are self-or externally generated.

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 extra-vestibular inputs such as proprioceptive and motor efference copy signals. Here we examined the neuronal correlates of this behavioral recovery after complete vestibular loss in alert behaving monkeys (Macaca mulata). We show for the first time that extra-vestibular inputs substitute for the vestibular inputs to stabilize gaze at the level of single neurons in the VOR premotor circuitry. The summed weighting of neck proprioceptive and efference copy information was sufficient to explain simultaneously observed behavioral improvements in gaze stability. Furthermore, by altering correspondence between intended and actual head movement we revealed a four-fold increase in the weight of neck motor efference copy signals consistent with the enhanced behavioral recovery observed when head movements are voluntary versus unexpected. Thus, taken together our results provide direct evidence that the substitution by extra-vestibular inputs in vestibular pathways provides a neural correlate for the improvements in gaze stability that are observed following the total loss of vestibular inputs.

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. The VOR was studied 1-39 days post-lesion using transient head perturbations (up to 12,000 degrees/s(2)), rapid rotations (up to 500 degrees/s), and sinusoidal rotations (up to 15 Hz). In response to rotations with high acceleration or velocity, both contra- and ipsilesional gains remained subnormal. VOR gains decreased as a function of increasing stimulus acceleration or velocity, reaching minimal values of 0.7-0.8 and 0.3-0.4 for contra and ipsilesional rotations, respectively. For sinusoidal rotations with low frequencies and velocities, responses to contralesional stimulation recovered within approximately 4 days. With increasing velocities and frequencies of rotation, however, the gains of contra- and ipsilesional responses remained subnormal. For each of the most challenging stimuli tested (i.e., 12,000 degrees/s(2 )transient head perturbations, 500 degrees/s fast whole-body rotations and 15 Hz stimulation) no significant compensation was observed in contra- or ipsilesional responses over time. Moreover, we found that gain of the cervico-ocular reflex (COR) remained negligible following unilateral loss indicating that neck reflexes did not contribute to the observed compensation. VOR responses elicited by both sinusoidal and transient rotations following unilateral labyrinthectomy could be described by the same mathematical model. We conclude that the compensated VOR has comparable response dynamics for impulses and sinusoidal head movements.