Sustained Loss of Bdnf Affects Peripheral but Not Central Vestibular Targets

The vestibular system is vital for proper balance perception, and its dysfunction contributes significantly to fall-related injuries, especially in the elderly. Vestibular ganglion neurons innervate vestibular hair cells at the periphery and vestibular nuclei and the uvula and nodule of the cerebellum centrally. During aging, these vestibular ganglion neurons degenerate, impairing vestibular function. A complete understanding of the molecular mechanisms involved in neurosensory cell survival in the vestibular system is unknown. Brain-derived neurotrophic factor (BDNF) is specifically required for the survival of vestibular ganglion neurons, as its loss leads to early neuronal death. Bdnf null mice die within 3 weeks of birth, preventing the study of the long-term effects on target cells. We use Pax2-cre to conditionally knock out Bdnf, allowing mice survival to approximately 6 months of age. We show that a long-term loss of Bdnf leads to a significant reduction in the number of vestibular ganglion neurons and a reduction in the number of vestibular hair cells. There was no significant decrease in the central targets lateral vestibular nucleus (LVN) or the cerebellum at 6 months. This suggests that the connectivity between central target cells and other neurons suffices to prevent their loss despite vestibular hair cell and ganglion neuron loss. Whether the central neurons would undergo eventual degeneration in the absence of Bdnf remains to be determined.

Sensorimotor Rehabilitation Promotes Vestibular Compensation in a Rodent Model of Acute Peripheral Vestibulopathy by Promoting Microgliogenesis in the Deafferented Vestibular Nuclei

Acute peripheral vestibulopathy leads to a cascade of symptoms involving balance and gait disorders that are particularly disabling for vestibular patients. Vestibular rehabilitation protocols have proven to be effective in improving vestibular compensation in clinical practice. Yet, the underlying neurobiological correlates remain unknown. The aim of this study was to highlight the behavioural and cellular consequences of a vestibular rehabilitation protocol adapted to a rat model of unilateral vestibular neurectomy. We developed a progressive sensory-motor rehabilitation task, and the behavioural consequences were quantified using a weight-distribution device. This analysis method provides a precise and ecological analysis of posturolocomotor vestibular deficits. At the cellular level, we focused on the analysis of plasticity mechanisms expressed in the vestibular nuclei. The results obtained show that vestibular rehabilitation induces a faster recovery of posturolocomotor deficits during vestibular compensation associated with a decrease in neurogenesis and an increase in microgliogenesis in the deafferented medial vestibular nucleus. This study reveals for the first time a part of the underlying adaptative neuroplasticity mechanisms of vestibular rehabilitation. These original data incite further investigation of the impact of rehabilitation on animal models of vestibulopathy. This new line of research should improve the management of vestibular patients.

Role of the trace amine associated receptor 5 (TAAR5) in the sensorimotor functions

Classical monoamines are well-known modulators of sensorimotor neural networks. However, the role of trace amines and their receptors in sensorimotor function remains unexplored. Using trace amine-associated receptor 5 knockout (TAAR5-KO) mice, that express beta-galactosidase mapping its localization, we observed TAAR5 expression in the Purkinje cells of the cerebellum and the medial vestibular nucleus, suggesting that TAAR5 might be involved in the vestibular and motor control. Accordingly, in various behavioral tests, TAAR5-KO mice demonstrated lower endurance, but better coordination and balance compared to wild-type controls. Furthermore, we found specific changes in striatal local field potentials and motor cortex electrocorticogram, such as a decrease in delta and an increase in theta oscillations of power spectra, respectively. The obtained data indicate that TAAR5 plays a considerable role in regulation postural stability, muscle force, balance, and motor coordination during active movements, likely via modulation of monoaminergic systems at different levels of sensorimotor control involving critical brain areas such as the brainstem, cerebellum, and forebrain.

Sound-Evoked Responses in the Vestibulo-Ocular Reflex Pathways of Rats

Vestibular evoked myogenic potentials (VEMP) have been used to assess otolith function in clinics worldwide. However, there are accumulating evidence suggesting that the clinically used sound stimuli activate not only the otolith afferents, but also the canal afferents, indicating canal contributions to the VEMPs. To better understand the neural mechanisms underlying the VEMPs and develop discriminative VEMP protocols, we further examined sound-evoked responses of the vestibular nucleus neurons and the abducens neurons, which have the interneurons and motoneurons of the vestibulo-ocular reflex (VOR) pathways. Air-conducted clicks (50–80 dB SL re ABR threshold, 0.1 ms duration) or tone bursts (60–80 dB SL, 125–4,000 Hz, 8 ms plateau, 1 ms rise/fall) were delivered to the ears of Sprague-Dawley or Long-Evans rats. Among 425 vestibular nucleus neurons recorded in anesthetized rats and 18 abducens neurons recorded in awake rats, sound activated 35.9% of the vestibular neurons that increased discharge rates for ipsilateral head rotation (Type I neuron), 15.7% of the vestibular neurons that increased discharge rates for contralateral head rotation (Type II neuron), 57.2% of the vestibular neurons that did not change discharge rates during head rotation (non-canal neuron), and 38.9% of the abducens neurons. Sound sensitive vestibular nucleus neurons and abducens neurons exhibited characteristic tuning curves that reflected convergence of canal and otolith inputs in the VOR pathways. Tone bursts also evoked well-defined eye movements that increased with tone intensity and duration and exhibited peak frequency of ∼1,500 Hz. For the left eye, tone bursts evoked upward/rightward eye movements for ipsilateral stimulation, and downward/leftward eye movements for contralateral stimulation. These results demonstrate that sound stimulation results in activation of the canal and otolith VOR pathways that can be measured by eye tracking devices to develop discriminative tests of vestibular function in animal models and in humans.

Understanding Vestibular Information Processing in Velocity-Storage Circuit and Application to Interpreting Clinical Manifestation of Vestibular Disorders

The velocity-storage circuit comprised of bilateral vestibular nucleus complexes, commissural fiber, and nodulus and uvula functions in refining the raw vestibular signal to estimate rotational velocity, gravity direction, and inertia. In this review, we pursued the functional significance of this velocity-storage circuit and how this physiologic knowledge could help us understand the clinical symptoms and signs of patients with vestibular disorders.

Hypergravity-induced malfunction was moderated by the regulation of NMDA receptors in the vestibular nucleus

Gravity alteration is one of the critical environmental factors in the space, causing various abnormal behaviors related with the malfunctioned vestibular system. Due to the high plastic responses in the central vestibular system, the behavioral failures were resolved in a short period of time (in approx. 72 h). However, the plastic neurotransmission underlying the functional recovery is still elusive. To understand the neurotransmitter-induced plasticity under hypergravity, the extracellular single neuronal recording and the immunohistochemistry were conducted in the vestibular nucleus (VN). The animals were grouped as control, 24-h, 72-h, and 15-day exposing to 4G-hypergravity, and each group had two subgroups based on the origins of neuronal responses, such as canal and otolith. The averaged firing rates in VN showed no significant difference in the subgroups (canal-related: p > 0.105, otolith-related: p > 0.138). Meanwhile, the number of NMDAr was significantly changed by the exposing duration to hypergravity. The NMDAr decreased in 24 h (p = 1.048 × 10–9), and it was retrieved in 72 h and 15 days (p < 4.245 × 10–5). Apparently, the reduction and the retrieval in the number of NMDAr were synchronized with the generation and recovery of the abnormal behaviors. Thus, the plasticity to resolve the hypergravity-induced malfunctional behaviors was conducted by regulating the number of NMDAr.

Neural Interruption by Unilateral Labyrinthectomy Biases the Directional Preference of Otolith-Related Vestibular Neurons

Background: The directional preference of otolith-related vestibular neurons elucidates the neuroanatomical link of labyrinths, but few direct experimental data have been provided. Methods: The directional preference of otolith-related vestibular neurons was measured in the vestibular nucleus using chemically induced unilateral labyrinthectomy (UL). For the model evaluation, static and dynamic behavioral tests as well as a histological test were performed. Extracellular neural activity was recorded for the neuronal responses to the horizontal head rotation and the linear head translation. Results: Seventy-seven neuronal activities were recorded, and the total population was divided into three groups: left UL (20), sham (35), and right UL (22). Based on directional preference, two sub-groups were again classified as contra- and ipsi-preferred neurons. There was no significance in the number of those sub-groups (contra-, 15/35, 43%; ipsi-, 20/35, 57%) in the sham (p = 0.155). However, more ipsi-preferred neurons (19/22, 86%) were observed after right UL (p = 6.056 × 10−5), while left UL caused more contra-preferred neurons (13/20, 65%) (p = 0.058). In particular, the convergent neurons mainly led this biased difference (ipsi-, 100% after right UL and contra-, 89% after left UL) (p < 0.002). Conclusions: The directional preference of the neurons depended on the side of the lesion, and its dominance was mainly led by the convergent neurons.