Adaptation of spatio-temporal convergent properties in central vestibular neurons in monkeys.

The spatio-temporal convergent (STC) response occurs in central vestibular cells when dynamic and static inputs are activated. The functional significance of STC behavior is not fully understood. Whether STC is a property of some specific central vestibular neurons, or whether it is a response that can be induced in any neuron at some frequencies is unknown. It is also unknown how the change in orientation of otolith polarization vector (orientation adaptation) affects STC behavior. A new complex model, that includes inputs with regular and irregular discharges from both canal and otolith afferents, was applied to experimental data to determine how many convergent inputs are sufficient to explain the STC behavior as a function of frequency and orientation adaptation. The canal-otolith and otolith-only neurons were recorded in the vestibular nuclei of three monkeys. About 42% (11/26 canal-otolith and 3/7 otolith-only) neurons showed typical STC responses at least at one frequency before orientation adaptation. After orientation adaptation in side-down head position for 2 h, some canal-otolith and otolith-only neurons altered their STC responses. Thus, STC is a property of weights of the regular and irregular vestibular afferent inputs to central vestibular neurons which appear and/or disappear based on stimulus frequency and orientation adaptation. This indicates that STC properties are more common for central vestibular neurons than previously assumed. While gravity-dependent adaptation is also critically dependent on stimulus frequency and orientation adaptation, we propose that STC behavior is also linked to the neural network responsible for localized contextual learning during gravity-dependent adaptation.

Contribution of vestibular efferent system alpha-9 nicotinic receptors to vestibulo-oculomotor interaction and short-term vestibular compensation after unilateral labyrinthectomy in mice.

Sudden unilateral loss of vestibular afferent input causes nystagmus, ocular misalignment, postural instability and vertigo, all of which improve significantly over the first few days after injury through a process called vestibular compensation (VC). Efferent neuronal signals to the labyrinth are thought to be required for VC. To better understand efferent contributions to VC, we compared the time course of VC in wild-type (WT) mice and α9 knockout (α9(-/-)) mice, the latter lacking the α9 subunit of nicotinic acetylcholine receptors (nAChRs), which is thought to represent one signaling arm activated by the efferent vestibular system (EVS). Specifically, we investigated the time course of changes in the fast/direct and slow/indirect components of the angular vestibulo-ocular reflex (VOR) before and after unilateral labyrinthectomy (UL). Eye movements were recorded using infrared video oculography in darkness with the animal stationary and during sinusoidal (50 and 100°/s, 0.5-5 Hz) and velocity step (150°/s for 7-10s, peak acceleration 3000°/s(2)) passive whole-body rotations about an Earth-vertical axis. Eye movements were measured before and 0.5, 2, 4, 6 and 9 days after UL. Before UL, we found frequency- and velocity-dependent differences between WT and α9(-/-) mice in generation of VOR quick phases. The VOR slow phase time constant (TC) during velocity steps, which quantifies contributions of the indirect component of the VOR, was longer in α9(-/-) mutants relative to WT mice. After UL, spontaneous nystagmus (SN) was suppressed significantly earlier in WT mice than in α9(-/-) mice, but mutants achieved greater recovery of TC symmetry and VOR quick phases. These data suggest (1) there are significant differences in vestibular and oculomotor functions between these two types of mice, and (2) efferent signals mediated by α9 nicotinic AChRs play a role during VC after UL.

Adaptation of orientation of central otolith-only neurons.

Otolith-only neurons were recorded extracellularly in the vestibular nuclei before and after cynomolgus monkeys were held on-side for up to 3 hr. The aim was to determine whether the polarization vectors of these neurons reorient toward the spatial vertical as do canal-otolith convergent neurons. Otolith input was characterized by tilting the animal 30 degrees from the upright position while positioning the head in different directions in yaw. This determined the response vector orientation (RVO), that is, the projection of the otolith polarization vector onto the head horizontal plane. Changes in the RVO of otolith-only neurons ranged from 2 degrees -16 degrees , which was on average considerably less than the changes previously noted in canal-otolith convergent vestibulo-only (VO) and vestibular plus saccade (VPS) neurons, which ranged up to 109 degrees. Some of the otolith-only neurons had marked sensitivity changes. These findings suggest that otolith-only neurons tend to maintain a head-fixed orientation during prolonged head tilts relative to gravity. In contrast, canal-convergent VO and VPS neurons optimize their response vector orientation to gravity when the head is oriented for prolonged periods.

Differential coding of head rotation by lateral-vertical canal convergent central vestibular neurons.

Convergent inputs from the lateral and vertical semicircular canals (LC and VC) to 31 central vestibular-only (VO) and vestibular-plus-saccade (VPS) neurons were determined by oscillating monkeys about a spatial vertical axis while the head was tilted forward and backward up to 90 degrees. Activity of each neuron varied as a function of head tilt. Seven neurons had maximal activation when the head was tilted approximately 30 degrees forward (spatial phase), indicating convergent inputs from the LC, while peak activation of 10 units occurred with the head tilted back approximately 50 degrees, indicating VC input. Fourteen neurons had spatial phases that deviated more that 15 degrees from the LC and VC planes, indicating convergent inputs from LC and VC. Seven of these neurons had a spatial phase less than 15 degrees forward and 35 degrees back, indicating canal inputs from both sides. Seven other neurons had spatial phases more that 45 degrees forward and 65 degrees back, indicating inputs from canals located on the same side. Thus, there are two groups of central vestibular neurons: one group responds maximally when the head is rotated about a spatial vertical axis in an upright position, declining as the head is tilted away from this position. Another group responds minimally to rotation in an upright head orientation, increasing as the head is tilted away from the upright. A majority of the cells also had convergent otolith input. The otolith and canal inputs superposed when the animals were rotated about roll and pitch axes from an upright position. This insured that these neurons would respond over a broad frequency range from very low to high frequencies.

Adaptation of orientation vectors of otolith-related central vestibular neurons to gravity.

Behavioral experiments indicate that central pathways that process otolith-ocular and perceptual information have adaptive capabilities. Because polarization vectors of otolith afferents are directly related to the electro-mechanical properties of the hair cell bundle, it is unlikely that they change their direction of excitation. This indicates that the adaptation must take place in central pathways. Here we demonstrate for the first time that otolith polarization vectors of canal-otolith convergent neurons in the vestibular nuclei have adaptive capability. A total of 10 vestibular-only and vestibular-plus-saccade neurons were recorded extracellularly in two monkeys before and after they were in side-down positions for 2 h. The spatial characteristics of the otolith input were determined from the response vector orientation (RVO), which is the projection of the otolith polarization vector, onto the head horizontal plane. The RVOs had no specific orientation before animals were in side-down positions but moved toward the gravitational axis after the animals were tilted for extended periods. Vector reorientations varied from 0 to 109 degrees and were linearly related to the original deviation of the RVOs from gravity in the position of adaptation. Such reorientation of central polarization vectors could provide the basis for changes in perception and eye movements related to prolonged head tilts relative to gravity or in microgravity.

Changes in the gaze fixation reaction in rhesus monkeys during the initial stage of water immersion.

The gaze fixation reaction was studied in three rhesus monkeys before and during thermoneutral (34.5 degrees C) water immersion to the mid-chest level. The angular vestibulo-ocular reflex gain increased and the head angular velocity decreased significantly in all monkeys in 5 h after the start of immersion. Additionally, one animal was immersed to the neck level. Two hours in the condition of more pronounced support deprivation decreased significantly angular velocity of the head but not increased the angular vestibulo-ocular reflex gain. Therefore, support deprivation act upon the head movement control first.