Vestibulo-ocular reflex of the squirrel monkey during eccentric rotation with centripetal acceleration along the naso-occipital axis

The vestibulo-ocular reflexes (VOR) are determined not only by angular acceleration, but also by the presence of gravity and linear acceleration. This phenomenon was studied by measuring three-dimensional nystagmic eye movements, with implanted search coils, in four male squirrel monkeys. Monkeys were rotated in the dark at 200°/s, centrally or 79 cm off-axis, with the axis of rotation always aligned with gravity and the spinal axis of the upright monkeys. The monkey's position relative to the centripetal acceleration (facing center or back to center) had a dramatic influence on the VOR. These studies show that a torsional response was always elicited that acted to shift the axis of eye rotation toward alignment with gravito-inertial force. On the other hand, a slow phase downward vertical response usually existed, which shifted the axis of eye rotation away from the gravito-inertial force. These findings were consistent across all monkeys. In another set of tests, the same monkeys were rapidly tilted about their interaural (pitch) axis. Tilt orientations of 45° and 90° were maintained for 1 min. Other than a compensatory angular VOR during the rotation, no consistent eye velocity response was ever observed during or following the tilt. The absence of any response following tilt proves that the observed torsional and vertical responses were not a positional nystagmus. Model simulations qualitatively predict all components of these eccentric rotation and tilt responses. These simulations support the conclusion that the VOR during eccentric rotation may consist of two components: a linear VOR and a rotational VOR. The model predicts a slow phase downward, vertical, linear VOR during eccentric rotation even though there was never a change in the force aligned with monkey's spinal (Z) axis. The model also predicts the torsional components of the response that shift the rotation axis of the angular VOR toward alignment with gravito-inertial force.     

Preferred axis of rotation of floccular Purkinje cells in the decerebrate cat

Responses of 35 Purkinje cells in decerebrate cats were recorded during 0.5 Hz rotations in 4–11 vertical planes and the horizontal plane to determine their semicircular canal input. Most neurons received convergent input from two canals (21 neurons) or 3 canals (5 neurons). Few Purkinje cells were maximally sensitive to rotations about an axis appropriate to their inferior olivary input as determined by Gerrits and Voogd [15,24,27,49].     

Dynamic characteristics of vestibular-driven compensatory fin movements of the dogfish

Compensatory pectoral fin reflexes were studied in decerebrate dogfish subjected to sinusoidal oscillation (0.01-1.0 Hz). At 0.01 Hz the peak response of the depressor muscle was in phase with head position. At higher frequencies the phase advanced and at 1 Hz approached that of maximum angular velocity. Peak response amplitude was steady from 0.01 to 0.07 Hz but thereafter increased markedly. We suggest that the high frequency response depends upon vertical semicircular canal input.     

Influence of long-term optokinetic stimulation on eye movements of the rabbit

Two kinds of optokinetic afternystagmus (OKAN) have been studied in rabbits; positive and negative OKAN. Positive OKAN is the persistence of eye movements evoked by optokinetic stimulation following the termination of the stimulus, with the slow phase of the eye movements in the same direction as the inducing stimulus. Negative OKAN is evoked by long duration optokinetic stimulation, and has a slow phase of opposite direction to the inducing stimulus. The stimulus conditions which are optimal for inducing and maintaining negative OKAN were characterized. Rabbits were placed in an optokinetic drum for periods of 12-96 h (with appropriate intervening periods for food and water). Eye movements were recorded during and after the termination of optokinetic stimulation. The optimum optokinetic stimulus velocity for the induction of negative OKAN was 5 degrees/s. The minimum duration of stimulation for the induction of negative OKAN of maximum velocity was 48 h. Once induced, the slow phase of negative OKAN attained velocities of 50-100 degrees/s. Three conditions of restraint of the rabbits were studied after negative OKAN was induced during the intervening periods when eye movements were not being recorded. These conditions were: (1) unrestrained (full freedom of movement) without visual stimulation (in a dark enclosure); (2) restrained (horizontal head and body movement prevented) without visual stimulation; and (3) restrained with visual stimulation (in the stationary optokinetic drum). Conditions 1 and 2 caused negative OKAN to dissipate within 24 h. Condition 3 caused negative OKAN to be maintained for more than 70 h. The velocity imbalance of the horizontal vestibuloocular reflex (HVOR) was measured at different times following the induction of negative OKAN. It provided a more sensitive index of the central imbalance which caused negative OKAN, than did spontaneous nystagmus. One of the consequences of optokinetic stimulation measured over a 16 h period was a decrease in the gain of the optokinetic reflex. This reduction in gain could represent a central adaptation to maintained stimulation which in the absence of continued optokinetic stimulation is expressed as a nystagmus.     

Central projections of the vestibular nerve: a review and single fiber study in the Mongolian gerbil

The primary purpose of this article is to review the anatomy of central projections of the vestibular nerve in amniotes. We also report primary data regarding the central projections of individual horseradish peroxidase (HRP)-filled afferents innervating the saccular macula, horizontal semicircular canal ampulla, and anterior semicircular canal ampulla of the gerbil.

In total, 52 characterized primary vestibular afferent axons were intraaxonally injected with HRP and traced centrally to terminations. Lateral and anterior canal afferents projected most heavily to the medial and superior vestibular nuclei. Saccular afferents projected strongly to the spinal vestibular nucleus, weakly to other vestibular nuclei, to the interstitial nucleus of the eighth nerve, the cochlear nuclei, the external cuneate nucleus, and nucleus y.

The current findings reinforce the preponderance of literature. The central distribution of vestibular afferents is not homogeneous. We review the distribution of primary afferent terminations described for a variety of mammalian and avian species. The tremendous overlap of the distributions of terminals from the specific vestibular nerve branches with one another and with other sensory inputs provides a rich environment for sensory integration.     

Activity of cerebellar Purkinje cells during fictitious scratch reflex in the cat

The activity of Purkinje cells (PCs) was recorded in the anterior lobe (the vermis and pars intermedia) and in the paramedian lobule of the cerebellum during the fictitious scratch reflex in thalamic cats immobilized with Flaxedil. In the anterior lobe, the activity of many PCs was rhythmically modulated in relation to the scratch cycle: they generated bursts of impulses separated by periods of silence. Different PCs were active in different phases of the scratch cycle. In many cases the discharge modulation was irregular: the burst duration and the discharge rate in the burst varied considerably in subsequent cycles. The rhythmical activity of PCs was determined by modulation of the frequency of 'simple spikes' reflecting the mossy fiber input. Generation of 'complex spikes' reflecting the climbing fiber input in most PCs was not related with the scratch rhythm. In the paramedian lobule, rhythmical modulation of PCs was practically absent. Rhythmical modulation of PCs in immobilized cats is determined by signals coming from the central spinal mechanism of scratching via the ventral spinocerebellar tract (VSCT) and the spinoreticulocerebellar pathway (SRCP). Results of separate transections of these pathways demonstrated that the VSCT plays the crucial role in modulating the PCs.     

Dependence of cat vestibulo-ocular reflex direction adaptation on animal orientation during adaptation and rotation in darkness

Four series of experiments investigated how adaptive changes in direction of the cat's vestibulo-ocular reflex (VOR) vary with position of the animal during adaptive training and postadaptive testing. In all experiments VOR was measured electrooculographically during rotations about earth-horizontal and vertical axes in the dark before and after 2 h of adaptation in which 0.25 Hz sinusoidal whole body rotation about a horizontal/vertical axis was paired with synchronous 0.25 Hz rotation of a visual pattern about a vertical/horizontal axis, respectively. In upright sagittal (US) experiments, coupling of pitch rotation with visual pattern rotation about an earth vertical axis yielded an adaptive horizontal VOR response to pitch rotation whose gain had a local maximum at 0.25-0.5 Hz plus a sustained rise for frequencies below 0.1 Hz. When post-tests were done with the animal rolled 90 degrees onto its side and rotated about the earth vertical axis (pitch relative to the cat), the low frequency rise was eliminated and the 0.25 Hz peak was reduced. In on side sagittal (SS) experiments, where training was done in the latter (on side) position, training produced only the 0.25 Hz peak without the low frequency rise, indicating that the rise is due to coupling of otolith input to horizontal VOR. Again the 0.25 Hz peak was reduced when testing was done with the cat oriented 90 degrees from the training position (in the US position). This indicates that the cross-coupled canal-ocular reflex response is modulated or gated by the position of the animal with respect to gravity.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of gravity on horizontal and vertical vestibulo-ocular and optokinetic reflexes in the rabbit

The influence of the linear acceleration of gravity on the vertical and horizontal vestibulo-ocular reflexes (VVOR, HVOR) as well as the vertical and horizontal optokinetic reflexes (VOKR, HOKR) has been examined in rabbits. Rabbits were mounted in a biaxial rate table in front of a rear projection tangent screen. Eye movements were measured with a light projection technique. The HVOR, VVOR, HOKR and VOKR were measured in rabbits which were maintained both prone and supine. The gain of the HVOR for the supine orientation was reduced at all frequencies tested (0.01-0.80 Hz). Similarly there was a reduction in the gain of the HOKR. By contrast, the gain of the VVOR in the supine orientation was enhanced over a lower range of frequencies (0.02-0.04 Hz) and reduced at higher frequencies (0.10-0.80 Hz). The gain of the VOKR was not reduced in the supine orientation. The range of eye positions over which compensatory eye movements occurred was restricted in the supine orientation. The altered orientation of the medio-laterally polarized hair cells of the utricular maculae with respect to gravity in the supine orientation may cause postural instability and facilitate 'righting reflexes'. A reduction in the gains of the HVOR, VVOR and HOKR caused by linear accelerations in the sagittal plane during locomotion may decrease automatic postural responses during certain movements in which these automatic postural adjustments would not necessarily be adaptive.     

Simple spike activity of Purkinje cells in the posterior vermis of awake cats during spontaneous saccadic eye movements

Extracellular recordings were made from 151 cerebellar cortical cells in the posterior vermis of 12 awake cats. Thirty-two percent (n=48) of these cells modulated their activity with respect to the onset of spontaneous saccadic eye movements. Thirty-five cells in this group were positively identified as Purkinje cells and manifested changes in simple spike activity that were related to saccade onset. These included short excitatory, inhibitory, or biphasic changes that were superimposed on background tonic firing rates (avg.=54 spikes/sec). Such changes were recorded before as well as after the onset of a saccade. Sixty-five percent (n=22) of these cells were related to horizontal and vertical saccades in more than one direction of motion. These cells were randomly distributed throughout the posterior vermis and manifested no anatomical topographic organization with respect to the direction of saccadic eye movement. The results of this study suggest that lobules VI and VII of the cerebellar vermis participate in both the initiation and execution of spontaneous saccades in preferred directions.     

Role of the otolith organs in generation of horizontal nystagmus: effects of selective labyrinthine lesions

The direct cellular effects of ethanol on trigeminal motoneurons were studied in chronic cats during sleep and wakefulness. Intracellular and extracellular recordings were obtained while simultaneously injecting ethanol microdroplets onto the surface (juxtacellularly) or within the soma (intracellularly) of these motoneurons. Juxtacellular ethanol injection resulted in a suppression of neuronal excitability as well as a reduction in the amplitude of action potentials and monosynaptically-induced excitatory postsynaptic potentials. Intracellular ethanol injection led to a slight increase in excitability (i.e. membrane depolarization); concurrently, however, there was a reduction in the amplitude of spike and synaptic potentials. We conclude that the predominant response of trigeminal motoneurons to the direct application of ethanol entails a dose-dependent reduction in membrane excitability in addition to a depression of excitatory synaptic transmission. This pattern of ethanol action was observed throughout the states of quiet sleep and active sleep as well as when the animal was awake.     

Behavior and physiology of the macaque vestibulo-ocular reflex response to sudden off-axis rotation: Computing eye translation

The vestibulo-ocular reflex (VOR) has historically been considered a computationally simple reflex: to stabilize images on the retina against imposed head rotation, the eyes must be counterrotated by an equal amount in the opposite direction. During almost any head rotation, however, the eyes are also translated. We show that the VOR compensates for 90% of this translation, and suggest a computational scheme by which this is done, based on a temporal dissection of the VOR response to sudden head rotation. An initial response that corrects only for imposed rotation is refined by a series of three temporally delayed corrections of increasing complexity. The first correction takes only head rotation and viewing distance into account; the second, head rotation, viewing distance, and otolith translation; and the third, head rotation, viewing distance, otolith translation, and translation of the eyes relative to the otoliths. Responses of type I gaze velocity Purkije (GVP) cells in the cerebellar flocculus and ventral paraflocculus of rhesus monkeys were recorded during sudden head rotation. We show that cell discharge was modulated both by axis location and by viewing distance, suggesting that GVP cells play a role in the VOR response to rotation-induced eye translation.     

Differential glial activation during the degeneration of Purkinje cells and mitral cells in the PCD mutant mice

Purkinje Cell Degeneration (PCD) mice harbor a nna1 gene mutation which leads to an early and rapid degeneration of Purkinje cells (PC) between the third and fourth week of age. This mutation also underlies the death of mitral cells (MC) in the olfactory bulb (OB), but this process is slower and longer than in PC. No clear interpretations supporting the marked differences in these neurodegenerative processes exist. Growing evidence suggests that either beneficial or detrimental effects of gliosis in damaged regions would underlie these divergences. Here, we examined the gliosis occurring during PC and MC death in the PCD mouse. Our results demonstrated different glial reactions in both affected regions. PC disappearance stimulated a severe gliosis characterized by strong morphological changes, enhanced glial proliferation, as well as the release of pro‐inflammatory mediators. By contrast, MC degeneration seems to promote a more attenuated glial response in the PCD OB compared with that of the cerebellum. Strikingly, cerebellar oligodendrocytes died by apoptosis in the PCD, whereas bulbar ones were not affected. Interestingly, the level of nna1 mRNA under normal conditions was higher in the cerebellum than in the OB, probably related to a faster neurodegeneration and stronger glial reaction in its absence. The glial responses may thus influence the neurodegenerative course in the cerebellum and OB of the mutant mouse brain, providing harmful and beneficial microenvironments, respectively. © 2012 Wiley Periodicals, Inc.     

Defective control and adaptation of reflex eye movements in mutant mice deficient in either the glutamate receptor delta2 subunit or Purkinje cells

The ionotropic glutamate receptor delta2 subunit (GluRdelta2) is selectively expressed in cerebellar Purkinje cells and is implicated in long-term depression, synaptic formation and elimination. To study the effect of GluRdelta2 deficiency on motor control, we measured the vestibulo-ocular reflex (VOR) and optokinetic response (OKR) induced by sinusoidal rotation of the animal and/or the surrounding screen in two GluRdelta2 mutant mice: a GluRdelta2 knockout mouse (delta2-/-) and a lurcher mouse with a point mutation in the GluRdelta2 gene resulting in loss of all Purkinje cells. delta2-/- showed significantly higher VOR gain in the dark (VORD) than in the wild-type. In delta2-/-, the VOR gain in light was lower than that in the dark. The phase of OKR lagged more in delta2-/- than in lurcher and wild-type mice. Both mutant mice failed to change the VORD or OKR gain adaptively in response to sustained vestibular and/or visual stimulation. Basal properties of VOR and OKR changed little by lesion of the flocculus, but they changed substantially by lesion of the inferior olivary nuclei (IO). The abnormal VOR gain and OKR phase delay were clearly reduced in delta2-/- by the latter lesion. Our results indicate that failures in the GluRdelta2-dependent synaptic regulation affect motor performance more severely than loss of cerebellar cortical outputs. This study suggests that the anomalies in delta2-/- are dependent on inputs from IO and that GluRdelta2 deficiency changed properties of not only the cerebellar cortex but also the brainstem neuronal pathways controlling reflex eye movements during development.     

Naturally occurring neuronal death during the postnatal development of Purkinje cells and their precerebellar afferent projections

Naturally occurring neuronal death plays a substantial developmental role in the building of the neural circuitries. The neuronal death caused by different cerebellar mutations is mostly of an apoptotic nature. Apart from the identity of the intrinsic mechanisms of the mutations, adult cerebellar mutants are a powerful tool to causally study the development of the cerebellar connectivity. Thus, studies on adult cerebellar neuronal cell death occurring in mouse mutants elucidate: (i) the dependence of the postsynaptic neurons on their partners, (ii) the ‘en cascade’ postsynaptic transneuronal degeneration after target-deprivation, and (iii) the close relationship between the molecular modular organization of the cerebellar cortex and dying Purkinje cells. Neuronal cell death has been extensively studied in developing olivocerebellar system. However, less data are available on the occurrence of naturally occurring neuronal death during the in vivo normal development of the Purkinje cells and the mossy fiber system neurons. The developmental role of neuronal death during the establishment and refinement of the olivocerebellar projection is currently discussed. Moreover, the occurrence of neuronal death during the development of the basilar pontine nuclei and its role in the acquisition of the adult pontocerebellar projection is still poorly understood. In the present review, we correlate the dates of Purkinje cells death with the inferior olivary and basilar pontine neuronal apoptosis, discussing their developmental relationships during the elaboration of the fine-grained maps of the cerebellar afferent connections.     

Simple spike and complex spike activity of floccular Purkinje cells during the optokinetic reflex in mice lacking cerebellar long-term depression

Cerebellar long-term depression (LTD) at parallel fibre-Purkinje cell (P-cell) synapses is thought to embody neuronal information storage for motor learning. Transgenic L7-protein kinase C inhibitor (PKCI) mice in which cerebellar LTD is selectively blocked do indeed exhibit impaired adaptation in the vestibulo-ocular reflex (VOR) while their default oculomotor performance is unaffected. Although supportive, these data do not definitively establish a causal link between memory storage required for motor learning and cerebellar LTD. As the L7-PKCI transgene is probably activated from the early stages of P-cell development, an alternative could be that P-cells develop abnormal signals in L7-PKCI mutants, disturbing mechanisms of motor learning that rely on proper P-cell outputs. To test this alternative hypothesis, we studied simple spike (SS) and complex spike (CS) activity of vertical axis P-cells in the flocculus of L7-PKCI mice and their wild-type littermates during sinusoidal optokinetic stimulation. Both SS and CS discharge dynamics appeared to be very similar in wild-type and transgenic P-cells at all stimulus frequencies (0.05-0.8 Hz). The CS activity of all vertical axis cells increased with contralateral stimulus rotation and lagged ipsiversive eye velocity by 165-180 degrees. The SS modulation was roughly reciprocal to the CS modulation and lagged ipsiversive eye velocity by approximately 15 degrees. The baseline SS and CS discharge characteristics were indistinguishable between the two genotypes. We conclude that the impaired VOR learning in L7-PKCI mutants does not reflect fundamental aberrations of the cerebellar circuitry. The data thus strengthen the evidence that cerebellar LTD is implicated in rapid VOR learning but not in the development of normal default response patterns.