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

Analyse und Modellierung vestibulärer Information in den tiefen Kleinhirnkernen

Das Ziel dieser Studie ist es, die Rolle des Kleinhirns bei der Verarbeitung vestibul ärer Signale besser zu verstehen. Entsprechend wurden in dem Experiment, auf welchem diese Arbeit aufbaut, Einzelzellableitungen rein vestibulärer Neurone im rostralen Nucleus fastigii von Affen (Macaca mulatta) durchgeführt. Die Affen wurden in einer Schaukelvorrichtung bei verschiedenen Frequenzen (0.06 - 1.4 Hz) und Orientierungen in vertikalen Ebenen einer sinusförmig vestibulären, passiven Stimulation unterzogen. Innerhalb einer Messung wurde hierbei die Stimulusfrequenz konstant gehalten, während die Stimulusorientierung langsam um 180 Grad gedreht wurde. In einem ersten Schritt wurden die 195 Messungen aus 28 Neuronen systemtheoretisch vorverarbeitet. Hierzu wurde hergeleitet, wie das Antwortsignal einer Messung bei dem gegebenen Stimulus unter der Annahme linearer spatio-temporaler Konvergenz, d.h. Konvergenz peripherer vestibulärer Afferenzen mit unterschiedlichen räumlichen und zeitlichen Eigenschaften, aussehen sollte. Mit der so erhaltenen Gleichung wurden die gemessenen neuronalen Entladungsraten gefittet. Es konnte dabei gezeigt werden, dass sich ein Großteil der Messungen gut fitten lässt. Die Neurone verhalten sich somit bei konstanter Stimulusfrequenz im allgemeinen wie lineare STC-Neurone. In Übereinstimmung mit Siebold et al. (1999) konnten dabei einige komplexe Eigenschaften der Neurone beobachtet werden. In vielen Messungen gibt es keine Stimulusorientierung, bei welcher der Gain verschwindet. Die Phasendifferenz zwischen Entladungsrate und Stimulus ändert sich hierbei langsam aber stetig mit der Stimulusorientierung. Bei einigen Neuronen konnte auch eine starke Abhängigkeit der Vorzugsorientierung von der Stimulusfrequenz beobachtet werden. Des weiteren ist die Phase in Richtung der Vorzugsorientierung oft stark frequenzabhängig. Darüber hinaus konnte mit dieser Fitprozedur zum ersten Mal gezeigt werden, dass der FN vermutlich einen Eingang aus dem Sakkulus erhält. Da der Sakkulus jedoch bei den verwendeten kleinen Stimulusamplituden nur wenig stimuliert wird, sollte dieses Ergebnis in zukünftigen Experimenten bei größeren Stimulusamplituden überprüft werden. Im Folgenden wurden 10 Messungen bei den Frequenzen 0.06 Hz und 0.1 Hz mit einem schlechten Signal-Rausch Verhältnis (geringer dynamischer Input, wenig Stimulusperioden) herausgenommen, so dass sich die Gesamtzahl der Messungen auf 185 reduzierte. Im nächsten Verarbeitungsschritt konnte gezeigt werden, dass sich die neuronalen Entladungsraten von 22 der 28 Neurone durch eine lineare Summation der Signale aus den Bogengängen und Otolithen fitten lassen. Die Qualität der Fits war bei den meisten Neuronen nur dann gut, wenn von einem Bogengangs- und zwei Otolitheneingängen, einem regulären und einem irregulären, ausgegangen wurde. Die Verwendung von nur einem Otolitheneingang führte im allgemeinen zu schlechten Fitergebnissen. Hierbei war es egal, welcher Art der Otolitheneingang - regulär, irregulär oder eine Mischung beider Typen - war. Die so berechneten Vorzugsorientierungen der Eingänge zeigten im allgemeinen entweder in etwa in die gleiche (Kanal- und reguläre Otolithenafferenz) oder entgegengesetzte (irregul äre Otolithenafferenz) Richtung. Hierdurch wurde eine mögliche Erklärung für das Zustandekommen der obigen, bis dahin unverstandenen komplexen Eigenschaften gewonnen. Unter der Annahme einer einfach gestalteten, zentralen, linearen Nachverarbeitung konnten noch vier weitere Neurone gefittet werden. Im Folgenden konnte eine relativ einfache systemtheoretische Beschreibung der Neurone durch zwei senkrecht aufeinanderstehende Transferfunktionen mit je fünf Parametern gefunden werden. 25 der 28 Neurone des FN können hierdurch im gesamten Frequenz- und Orientierungsbereich als lineare STC-Neurone beschrieben werden. Im letzten Teil der Arbeit konnte in einer Computersimulation gezeigt werden, dass bereits eine lineare Summation der Signale aus den Bogengängen und Otolithen genügt, um ein simuliertes zweidimensionales Pendel aufrecht zu halten, d.h. seine subjektive Vertikale zu bestimmen. Das sich im Gravitationsfeld befindliche Pendel besitzt in seinem Kopf (oberes Ende) simulierte Bogengänge und Otolithen. Diese geben ihre Signale direkt an simulierte Muskeln an seinem unteren Ende weiter. Diese einfache Rückkopplung genügt bereits, um dem simulierten Pendel im Gravitationsfeld die aufrechte Haltung zu ermöglichen und Störungen in Form von äußeren Kräften entgegenzuwirken

Direction discrimination thresholds of vestibular and cerebellar nuclei neurons

To understand the roles of the vestibular system in perceptual detection and discrimination of self-motion, it is critical to account for response variability in computing the sensitivity of vestibular neurons. Here we study responses of neurons with no eye movement sensitivity in the vestibular (VN) and rostral fastigial (FN) nuclei using high frequency (2 Hz) oscillatory translational motion stimuli. The axis of translation (i.e., heading) varied slowly (1°/s) in the horizontal plane as the animal was translated back and forth. Signal detection theory was used to compute the threshold sensitivity of VN/FN neurons for discriminating small variations in heading around all possible directions of translation. Across the population, minimum heading discrimination thresholds averaged 16.6° ±1° SE for FN neurons and 15.3°±2.2° SE for VN neurons, several-fold larger than perceptual thresholds for heading discrimination. In line with previous studies and theoretical predictions, maximum discriminability was observed for directions where firing rate changed steeply as a function of heading, which occurs at headings approximately perpendicular to the maximum response direction. Forward/backward heading thresholds tended to be lower than lateral motion thresholds, and the ratio of lateral over forward heading thresholds averaged 2.2±6.1 (geometric mean ± SD) for FN neurons and 1.1±4.4 for VN neurons. Our findings suggest that substantial pooling and/or selective decoding of vestibular signals from the vestibular and deep cerebellar nuclei may be important components of further processing. Such a characterization of neural sensitivity is critical for understanding how early stages of vestibular processing limit behavioral performance

Macaque parieto-insular vestibular cortex: Responses to self-motion and optic flow

The parieto-insular vestibular cortex (PIVC) is thought to contain an important representation of vestibular information. Here we describe responses of macaque PIVC neurons to three-dimensional (3D) vestibular and optic flow stimulation. We found robust vestibular responses to both translational and rotational stimuli in the retroinsular (Ri) and adjacent secondary somatosensory (S2) cortices. PIVC neurons did not respond to optic flow stimulation, and vestibular responses were similar in darkness and during visual fixation. Cells in the upper bank and tip of the lateral sulcus (Ri and S2) responded to sinusoidal vestibular stimuli with modulation at the first harmonic frequency, and were directionally tuned. Cells in the lower bank of the lateral sulcus (mostly Ri) often modulated at the second harmonic frequency, and showed either bimodal spatial tuning or no tuning at all. All directions of 3D motion were represented in PIVC, with direction preferences distributed roughly uniformly for translation, but showing a preference for roll rotation. Spatio-temporal profiles of responses to translation revealed that half of PIVC cells followed the linear velocity profile of the stimulus, one-quarter carried signals related to linear acceleration (in the form of two peaks of direction selectivity separated in time), and a few neurons followed the derivative of linear acceleration (jerk). In contrast, mainly velocity-coding cells were found in response to rotation. Thus, PIVC comprises a large functional region in macaque areas Ri and S2, with robust responses to 3D rotation and translation, but is unlikely to play a significant role in visual/vestibular integration for self-motion perception

RESPONSES OF PARABRACHIAL NUCLEUS NEURONS TO WHOLE-BODY MOTION IN THE MACAQUE

Projections from the vestibular nuclei to the parabrachial complex (PB) have been described in rats, rabbits, and monkeys, and have been proposed as a neuronal substrate for clinically-observed linkages between disorders of balance and of affect. This raised the questions of whether PB units respond to vestibular stimulation, and what details of whole-body motion are present in PB. The caudal two-thirds of the parabrachial and Kölliker-Fuse nuclei were explored by Balaban and coworkers (2002), and found to contain neurons responsive to whole-body, periodic rotations in vertical and horizontal planes. Responses to brief 'position trapezoid' stimuli indicated that PB units were sensitive to both angular velocity and static tilt, consistent with the presence of angular- and linear-acceleration sensitive inputs from the vestibular nuclei. In the majority of units, responses to brief static tilts (of 1.5s duration) appeared to reflect a sensitivity to linear acceleration in the head-horizontal plane, consistent with the presence of linear-acceleration sensitive inputs from the vestibular nuclei. We have replicated these results and further investigated the linear acceleration sensitivity of PB units using off-vertical axis rotations (OVAR). We have confirmed the general hypothesis that responses of many PB units to a rotating linear acceleration vector are consistent with the behavior of first- and second-order vestibular neurons. The majority of units responded to OVAR in a manner consistent with responses of vestibular neurons previously described as linear, one-dimensional accelerometers. Fewer units showed a variety of responses consistent with previously described central vestibular neurons suggestive of convergence of labyrinthine inputs with different spatial and temporal response properties, as well as prominent 'bias' type responses consisting of significant changes in mean firing rate during rotation, in the absence of significant modulation

Relationship between complex and simple spike activity in macaque caudal vermis during three-dimensional vestibular stimulation

Lobules 10 and 9 in the caudal posterior vermis [also known as nodulus and uvula (NU)] are thought important for spatial orientation and balance. Here, we characterize complex spike (CS) and simple spike (SS) activity in response to three-dimensional vestibular stimulation. The strongest modulation was seen during translation (CS: 12.8 ± 1.5, SS: 287.0 ± 23.2 spikes/s/G, 0.5 Hz). Preferred directions tended to cluster along the cardinal axes (lateral, fore-aft, vertical) for CSs and along the semicircular canal axes for SSs. Most notably, the preferred directions for CS/SS pairs arising from the same Purkinje cells were rarely aligned. During 0.5 Hz pitch/roll tilt, only about a third of CSs had significant modulation. Thus, most CSs correlated best with inertial rather than net linear acceleration. By comparison, all SSs were selective for translation and ignored changes in spatial orientation relative to gravity. Like SSs, tilt modulation of CSs increased at lower frequencies. CSs and SSs had similar response dynamics, responding to linear velocity during translation and angular position during tilt. The most salient finding is that CSs did not always modulate out-of-phase with SSs. The CS/SS phase difference varied broadly among Purkinje cells, yet for each cell it was precisely matched for the otolith-driven and canal-driven components of the response. These findings illustrate a spatiotemporal mismatch between CS/SS pairs and provide the first comprehensive description of the macaque NU, an important step toward understanding how CSs and SSs interact during complex movements and spatial disorientation

Phase-Linking and the Perceived Motion during Off-Vertical Axis Rotation

Human off-vertical axis rotation (OVAR) in the dark typically produces perceived motion about a cone, the amplitude of which changes as a function of frequency. This perception is commonly attributed to the fact that both the OVAR and the conical motion have a gravity vector that rotates about the subject. Little-known, however, is that this rotating-gravity explanation for perceived conical motion is inconsistent with basic observations about self-motion perception: (a) that the perceived vertical moves toward alignment with the gravito-inertial acceleration (GIA) and (b) that perceived translation arises from perceived linear acceleration, as derived from the portion of the GIA not associated with gravity. Mathematically proved in this article is the fact that during OVAR these properties imply mismatched phase of perceived tilt and translation, in contrast to the common perception of matched phases which correspond to conical motion with pivot at the bottom. This result demonstrates that an additional perceptual rule is required to explain perception in OVAR. This study investigates, both analytically and computationally, the phase relationship between tilt and translation at different stimulus rates—slow (45°/s) and fast (180°/s), and the three-dimensional shape of predicted perceived motion, under different sets of hypotheses about self-motion perception. We propose that for human motion perception, there is a phase-linking of tilt and translation movements to construct a perception of one’s overall motion path. Alternative hypotheses to achieve the phase match were tested with three-dimensional computational models, comparing the output with published experimental reports. The best fit with experimental data was the hypothesis that the phase of perceived translation was linked to perceived tilt, while the perceived tilt was determined by the GIA. This hypothesis successfully predicted the bottom-pivot cone commonly reported and a reduced sense of tilt during fast OVAR. Similar considerations apply to the hilltop illusion often reported during horizontal linear oscillation. Known response properties of central neurons are consistent with this ability to phase-link translation with tilt. In addition, the competing “standard” model was mathematically proved to be unable to predict the bottom-pivot cone regardless of the values used for parameters in the model

Vestibular Compensation: A spinovestibular mediated process.

Changes in posture are detected by the central nervous system through a number of sensory afferents. The vestibular labyrinths are one such sensor that discern rotational and accelerative movements of the head. The vestibular nuclei, the primary processor of labyrinthine input, coordinates several system outputs to maintain stable balance, visual gaze, and autonomic control in response to changes in posture. Following destruction of bilateral labyrinths, organisms are unable to effectively interact with their environment. Over time, these animals adapt due to some currently undefined process. It is our hypothesis that the observed behavioral recovery is due to a process that occurs within the vestibular nuclei. The nuclei regain their functional ability to sense changes in posture through substitution of sensory inputs from remaining non-labyrinthine afferents. Ascending spinovestibular afferents are ideal sources of plasticity, as they are ideally situated to convey this postural information. Recordings were made from the vestibular nuclei of decerebrate cats that had undergone a combined bilateral labyrinthectomy and vestibular neurectomy 49-103 days previously and allowed to recover. Responses of neurons were recorded to tilts in multiple vertical planes at frequencies ranging from 0.05 to 1 Hz and amplitudes up to 15°. The firing of 27% of the neurons was modulated by tilt. These findings show that activation of vestibular nucleus neurons during vertical rotations is not exclusively the result of labyrinthine inputs, and suggest that limb and trunk inputs may play an important role in graviception and modulating vestibular-elicited reflexes. In the second portion of this work, we examined the spinal contributions to the vestibular nuclei in both labyrinthectomized and normal animals. The large majority (72%) of vestibular nucleus neurons in labyrinth-intact animals whose firing was modulated by vertical rotations responded to electrical stimulation of limb and/or visceral nerves; the activity of even more vestibular nucleus neurons (93%) was affected by limb or visceral nerve stimulation in chronically labyrinthectomized preparations. These data suggest that nonlabyrinthine inputs elicited during movement will modulate the gain of responses elicited by the central vestibular system, and may provide for the recovery of spontaneous activity of vestibular nucleus neurons following peripheral vestibular lesions

Räumliche Organisation der linearen und angulären vestibulo-okulären Reflexe beim Grasfrosch (Rana temporaria)

Horizontale, vertikale und torsionale kanal-okuläre und entsprechende makulo-okuläre Reflexe wurden bei Fröschen getrennt untersucht. Ziel der Untersuchung war es einerseits, die räumlichen Vektoren der Richtungen von Bestantworten zu bestimmen und andererseits, die Vektororientierungen beider Reflexe zueinander in Beziehung zu setzen. Hierzu wurden die Summenaktionspotentiale von drei verschiedenen Augenmuskelnerven (M. lateralis rectus, M. inferior rectus, M. inferior obliquus) während Translations- bzw. Drehbeschleunigungen unter Ausschluß visueller Reizung untersucht. Sinusförmige Translationsbeschleunigungen wurden in horizontaler, vertikaler und schräger Richtung ausgeführt. Sinusförmige Drehbeschleunigungen wurden um eine erdvertikale Achse ausgeführt. Vor jeder Messung wurde die Kopfposition systematisch in der Nick- bzw. Kippebene verändert, um diejenigen Richtungen zu bestimmen, die maximale Antworten im Augenmuskelnerven auslösten. Anhand dieser Daten und anhand bekannter, kopffester Koordinaten der Bogengänge konnten die Richtungen der maximalen Antworten bei Translations- und Drehbeschleunigungen für die getesteten Augenmuskelnerven berechnet und in Bogengangskoordinaten ausgedrückt werden. Horizontale lineare Translationsbeschleunigungen riefen Antworten in den jeweiligen Augenmuskelnerven hervor. Jedem der getesteten Nerven konnte ein fächerförmiger Sektor auf dem kontralateralen Utrikel zugeordnet werden, aus dem die Antworten stammten. Die Antworten waren nur erregender Art, ein unterstützender hemmender makulo-okulärer Reflex konnte nicht festgestellt werden. Sakkulus oder Lagena steuerten keine vertikale Komponente zum makulo-okulären Reflex bei. Die Sektoren des M. lateralis rectus bzw. des M. inferior obliquus hatten einen Öffnungswinkel von 60° bzw. 45° und lagen in der rostralen Hälfte des Utrikels. Beide Sektoren überlappten und lagen in der Ebene der horizontalen Bogengänge. Der Sektor des M. inferior rectus war vergleichsweise schmal (5° Öffnungswinkel), lag in der kaudalen Hälfte des Utrikels und war um 6° gegenüber den horizontalen Bogengängen nach oben geneigt. Bei Drehbeschleunigungen traten maximale Antworten im Nerven des M. inferior obliquus auf, die sich aus der Konvergenz von Signalen vom kontralateralen anterioren und ipsilateralen horizontalen Bogengang (Konvergenzverhältnis 50 : 50) ergaben. Der Abduzensnerv antwortete maximal bei Rotationen in einer Ebene, bei der eine Konvergenz von Signalen aus dem kontralateralen horizontalen und anterioren Bogengang im Verhältnis 80 : 20 aktiviert wurde. Die Antworten im Nerven des M. inferior rectus waren maximal, wenn der Kopf in der Ebene des kontralateralen posterioren Bogengangs gedreht wurde. Ein Vergleich der Vektororientierungen der maximalen Antworten bei Translations- bzw. Drehbeschleunigungen zeigte, daß diese beiden Vektoren bei jedem der untersuchten Augenmuskelnerven jeweils etwa senkrecht zueinander standen. Mit dieser Anordnung können sich makulo-okuläre und kanal-okuläre Reflexe bestmöglich unterstützen: Die Richtung der Bestantworten bei Drehbeschleunigungen bleibt dieselbe, unabhängig davon, ob kanal-okuläre Reflexe isoliert oder zusammen mit makulo-okulären Reflexen aktiviert werden. Die hier gefundenen Unterschiede in der Organisation zwischen makulo- und kanal-okulären Reflexen sowie die gemeinsame räumliche Abstimmung der beiden Reflexe könnten ein allgemeines Organisationsprinzip bei Vertebraten darstellen

Behavioral Impairment in Aquatic Organisms Exposed to Neurotoxic Pollutants

Neuroactive chemicals are the largest group of micropollutants present in European rivers. There is increasing concern about the behavioral effects of these neuroactive chemicals on aquatic wildlife, potentially resulting in detrimental effects on individual, population, and community levels of ecological organization. This Special Issue, titled “Behavioral Impairment in Aquatic Organisms Exposed to Neurotoxic Pollutants”, presents original research and review articles addressing behavioral impairment induced by different aquatic invertebrate and vertebrate species to neuroactive chemicals. The selected studies include different methodological approaches, such as multi-compartment, automated plug and play, and homemade setups systems. We believe that this collection provides essential information regarding research and challenges on the behavioral ecotoxicity of invertebrate and vertebrate aquatic organisms, as well as the molecular mechanisms behind these effects