Abstract The contribution of neck proprioceptive sig-nals to signal processing in the vestibular nucleus wasstudied by recording responses of secondary horizontalcanal-related neurons to neck rotation in the squirrelmonkey. Responses evoked by passive neck rotationwhile the head was held stationary in space were com-pared with responses evoked by passive whole body ro-tation and by forced rotation of the head on the trunk.Most neurons (76%; 45/59) were sensitive to neck rota-tion. The nature and strength of neck proprioceptive in-puts varied and usually combined linearly with vestibu-lar inputs. In most cases (94%), the direction of the neckproprioceptive input was “antagonistic” or “reciprocal”with respect to vestibular sensitivity and, consequently,reduced the vestibular response during head-on-trunk ro-tation. Different types of vestibular neurons received dif-ferent types of proprioceptive input. Neurons whose firing behavior was related to eye position (position-vestibular-pause neurons and position-vestibular neu-rons) were often sensitive to the position of the headwith respect to the trunk. The sensitivity to head positionwas usually in the same direction as the neuron’s eye po-sition sensitivity. Non-eye-movement related neuronsand eye-head-velocity neurons exhibited the strongestsensitivity to passive neck rotation and had signals thatwere best related to neck velocity. The results suggestthat neck proprioceptive inputs play an important role inshaping the output of the primate vestibular nucleus andits contribution to posture, gaze and perception.
The vestibular endorgans detect the position and move-ment of the head. When this sensory information arrivesin the vestibular nuclei, it is combined with other sensoryand motor estimates of head movement. Non-vestibularestimates of head motion include optokinetic inputs(Henn et al. 1974), neck efference copy inputs related toneck movement commands (McCrea et al. 1999), andproprioceptive inputs from the neck (Anastasopoulos andMergner 1982; Magnus 1924; Pompeiano and Barnes1971; Wilson et al. 1966, 1968). The coordinates and dy-namics of each head movement estimate differ in impor-tant ways, but each is capable of evoking postural andoculomotor reflexes (Horak et al. 1990, 1994; Macphersonand Inglis 1993; McCollum et al. 1996) and a percept ofself motion or vertigo (Mergner et al. 1983, 1991, 1993).
Neck proprioceptors provide information regardingthe position and movement of the head with respect tothe trunk rather than movement of the head in space, butthese sensory signals nevertheless affect vestibular re-flexes that function to stabilize the posture of the eyes,head, and body as well as construct percepts of spatialorientation. Stimulation of neck muscle receptors hasprofound effects on the posture of the trunk and limbs(Lindsay et al. 1976; Magnus 1924; Roberts 1978) andactivates powerful vestibulo-spinal reflexes that helpmaintain a stable relationship between the head and thetrunk (Boyle and Pompeiano 1981; Kasper and Thoden1981; Peterson et al. 1985; Wilson et al. 1990). Posturalreflexes evoked by neck proprioceptive stimulation, suchas the cervicocollic reflex, may play an important role incompensating for the loss of vestibular reflexes in canal-plugged animals (Peterson and Goldberg 1982) and inlabyrinthine-deficient patients (Glasauer et al. 1994; deGraaf et al. 1992; Heimbrand et al. 1990; Horak et al.1994; Leigh et al. 1987; Maurer et al. 1998; Schweigartet al. 1993). Neck proprioceptive signals also affect sig-nal processing in pathways related to the vestibulo-ocular reflex (VOR). Stimulation of neck muscles pro-duces nystagmus (Hikosaka and Maeda 1973; Maeda
G. T. Gdowski · R. A. McCrea (✉ )Department of Neurobiology, Pharmacology and Physiology,Committee on Neurobiology, University of Chicago, 5806 S. Ellis Ave., Chicago, IL 60637, USAe-mail: [email protected].: +1-773-7026374 or +1-773-8340579, Fax: +1-773-834-0579
Exp Brain Res (2000) 135:511–526DOI 10.1007/s002210000542
R E S E A R C H A RT I C L E
Greg T. Gdowski · Robert A. McCrea
Neck proprioceptive inputs to primate vestibular nucleus neurons
1979; Thoden and Schmidt 1979), and dynamic rotationof the body around a stable head produces a cervico-ocular reflex that has been suggested to help labyrinthec-tomized patients stabilize gaze during head-on-trunkmovements (Bronstein and Hood 1986; Kasai and Zee1978; Leigh et al. 1987). Finally, stimulation of neckproprioceptors can produce a percept of self motion orvertigo in the absence of competing visual reafferentfeedback (Mergner et al. 1983, 1991, 1993).
It seems likely that the behavioral effects of neck af-ferent stimulation, in part, may be due to the effect ofneck proprioceptive input to vestibular neurons. Thepresence of neck proprioceptive signals on vestibular nucleus neurons is well documented in a variety of spe-cies (Anastasopoulos and Mergner 1982; Boyle andPompeiano 1980; Fredrickson et al. 1966; Fuller 1988;Kasper and Thoden 1981; Kasper et al. 1988; Pompeianoand Barnes 1971; Pompeiano et al. 1987; Wilson et al.1990). The inputs appear to provide both static and dy-namic estimates of head-on-trunk movement to second-ary vestibular neurons (Anastasopoulos and Mergner1982; Fuller 1988; Khalsa et al. 1988; Manzoni et al.1998). They are usually antagonistic to vestibular signalsduring passive head-on-trunk rotation (Anastasopoulosand Mergner 1982; Boyle and Pompeiano 1981; Kasperet al. 1988).
In this study, the neck proprioceptive input to hori-zontal canal-related neurons in the vestibular nuclei wasevaluated from responses during changes in static headposition following active gaze shifts and during passiveneck rotation in squirrel monkeys. Neurons were classi-fied based on responses during passive whole body rota-tion and during voluntary eye and head movements. Wereport that most neurons in the squirrel monkey vestibu-lar nuclei, like their counterparts in the cat, received
neck proprioceptive input, but that the strength and dy-namic characteristics of these signals varied significantlyin different classes of neurons.
Materials and methods
Single unit recordings from alert, head-free squirrel monkeys
Most experimental methods have been previously described(Gdowski and McCrea 1999; McCrea et al. 1999) and all adheredto the principles of laboratory animal care (NIH publication no.86–23). Three adult squirrel monkeys were surgically prepared forchronic recordings of gaze movements, single unit neural activity,and electrical stimulation of both labyrinths. During experiments,the monkeys were seated in a Plexiglas chair on a vestibular turn-table. Trunk movements with respect to the turntable were inhibit-ed with a shoulder harness and by the shape of the chair. The ex-perimental apparatus was designed to permit head-on-trunk yawmovements (±40°) about the C1–C2 axis in the plane of the hori-zontal semicircular canals. This was accomplished by attachingthe animal’s head to a vertical rod that rotated within a ball bear-
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Fig. 1A–C Experimental paradigms used to assess a neuron’s ves-tibular and neck proprioceptive input. A Whole body rotation(vestibular stimulation). B Passive neck rotation (trunk-on-headrotation). C Head-on-trunk rotation (combined vestibular and neckstimulation). Head-on-trunk movements during whole body rota-tion were usually restricted by fixing the vertical rod attached tothe animal’s head to the table with a block assembly (a). Neck ro-tation was produced by rotating the animal’s trunk with the turnta-ble while the head was held stationary in space with a rod thatconnected the vertical rod attached to the animal’s head to the ceil-ing (c) and by disabling the universal joint (b). The animal’s headwas rotated on its trunk either manually or with a ceiling-mountedmotor (d) while the body and trunk were held stationary in space.A shoulder harness (not shown) was used to prevent trunk move-ments with respect to the turntable. Eye and head movements wererecorded with respect to the turntable (field coils located on thevestibular turntable are not shown)
ing assembly attached to the table (Fig. 1A, a). A universal jointlocated above the animal’s head, in-line with the vertical rod, per-mitted small postural adjustments (Fig. 1B, b). The magneticsearch coil technique was used to measure horizontal and verticalgaze position and horizontal head position. Torsional eye move-ments were not measured. The field coils of the system (Neuroda-ta) were mounted on the turntable (not shown in Fig. 1) in order tomeasure position signals with respect to the turntable (i.e., trunk).Turntable velocity was measured with an angular velocity sensor(Watson). Single unit activity was recorded with epoxy-insulatedTungsten microelectrodes.
Gaze and head position signals from the output of the searchcoil system, turntable velocity, and instantaneous neuronal firingrate were low-pass filtered (5–10 kHz), sampled at 200 or 500 Hzwith an analog-to-digital (A/D) converter, and stored on a personalcomputer system. The data were analyzed on a Macintosh comput-er system using IGOR (Wavemetrics). Eye position with respect tothe head was computed by subtracting the head position signalfrom the gaze position signal. Head and eye velocity were digital-ly computed by differentiating and filtering the position wave-forms (low-pass smoothing, 20–50 Hz).
The microelectrode location within the vestibular nuclei wasverified by characteristics of the monosynaptically evoked fieldpotentials following electrical stimulation (0.1 ms monophasicperilymphatic cathodal pulses, 50–300 µA) of the ipsilateral ves-tibular nerve. Neurons were considered to have received a mono-synaptic input from the vestibular nerve if a single shock stimula-tion below 500 µA evoked a spike at a latency of less than 1.4 ms.The firing behavior of neurons in nearby structures (e.g., the abdu-cens nucleus, the prepositus nucleus, and vestibular nerves) wereused in conjunction with the vestibular evoked field potentials toaid in locating recording tracks. In one monkey, horseradish per-oxidase was deposited using a micro-syringe that was stereotaxic-ally placed at the recording sites to confirm the track locations(Gdowski and McCrea 1999; McCrea et al. 1999).
Experimental protocols
Figure 1 illustrates the experimental paradigms that were used.The neuron’s vestibular sensitivity was assessed from responses tosinusoidal whole-body rotation (WBR) produced with the vestibu-lar turntable (Fig. 1A) at 0.5 Hz (40°/s peak velocity) or at 2.3 Hz(20°/s peak velocity). Neuronal responses were assessed whenhead-on-trunk movements were absent or restricted (Fig. 1A, a).For neuron classification purposes, on some occasions the neuralresponses were recorded when the monkey fixated on a table-stationary visual target to cancel the vestibulo-ocular reflex duringWBR and when the monkey pursued moving visual targets withsmooth eye movements. In each case, visual targets were project-ed on a cylindrical screen located 90 cm in front of the monkey(not shown in Fig. 1).
Neck afferent input to neurons was assessed in three ways. Ineach case, rotations were produced in the plane of the horizontalsemicircular canals. First, sensitivity to static head-on-trunk posi-tion was evaluated using a regressive analysis of neuronal firingrate with angular head-on-trunk position from periods when thehead was stationary (>50 ms) following the production of sponta-neous head movements by the monkey. Second, neck afferentswere dynamically stimulated by passive rotation of the trunk whilethe head was held stationary in space (passive neck rotation; PNR,Fig. 1B). The head was stabilized by connecting a second rodfrom the ceiling to the vertical rod attached to the animal’s head(Fig. 1B, b) while the turntable was rotated (either 0.5 Hz, 40°/speak velocity, or 2.3 Hz, 20°/s peak velocity). Lastly, combinedvestibular and neck afferent stimulation was produced by passiverotation of the head with respect to the trunk (head-on-trunk rota-tion; HTR, Fig. 1C). The rod attached to the monkey’s head wasrotated manually or with a stepping motor (Fig. 1C, d) mounted onthe ceiling. Head-on-trunk rotations were usually produced at thesame stimulus frequencies used for PNR and WBR (e.g., 0.5 Hzand 2.3 Hz).
Data analysis
Neuronal sensitivity to eye and head position
The methods used for assessing neural sensitivity to eye positionand eye velocity were similar to those previously described (Cullen and McCrea 1993). Neural sensitivity to eye and head po-sition was estimated with multiple regression analysis. Typically,50–100 estimates of the mean firing rate, eye position, and head-on-trunk position were used in the analysis. Each estimate wascomputed over an interval of 50–100 ms when the head was sta-tionary. The data set included head positions, which ranged atleast ±20°, but did not exceed 40° from the center position. Theregression coefficients for each variable were used as an estimateof neuronal sensitivity to horizontal eye (ke) and head-on-trunk(kHT) position.
Neuronal sensitivity to dynamic rotations
Responses to dynamic WBR and PNR were studied primarily withperiodic, sinusoidal stimuli. The A/D samples of instantaneousneuronal firing rate, the position and velocity of the eye, head, andturntable were averaged across several stimulus cycles, sample bysample, with respect to the stimulus period. A/D samples that cor-responded to periods when saccades were produced were excludedfrom the records of gaze, eye and head position and velocity, andneural firing rate before averaging. Typically, periods of 30 ms be-fore the onset of the saccadic gaze shift and 40 ms after the end ofthe gaze shift were excluded from the analysis. The remaining“desaccaded” waveforms were screened to exclude periods whenthe monkey was judged inattentive or when gaze or neck positionwas eccentric by more than 20°. The gain and phase of neural andbehavioral responses were estimated by linear regression of a si-nusoidal function whose frequency was the same as the fundamen-tal frequency of the stimulus.
By convention, the phase of the neural response during PNRwas computed with respect to velocity of the head re trunk. Thehead movement with respect to the trunk was the opposite to thatof the turntable motion (trunk re space) during PNR, because thehead was stabilized in space. All figures illustrating PNR respons-es show the head movement with respect to the trunk. This con-vention transforms the coordinates of turntable motion (re space)during PNR into head coordinates and facilitates comparisonswith the responses during WBR and HTR, which are also in headcoordinates. The gain and phase of the PNR response are denotedwith TS (trunk in space) subscripts to distinguish them from re-sponses during forced head-on-trunk rotation (HTR).
Occasionally, small head movements in space occurred duringPNR, which were detected as differences between the turntablevelocity (trunk) and the head velocity signal (re trunk) derivedfrom the head position signal. These were likely produced by theflexibility of the delrin rod that was used to maintain the animal’shead stationary in space. In those cases, the scalar product of thehead movement in space (velocity and acceleration) and the neu-ron’s decomposed velocity and acceleration sensitivities duringWBR (described below) were subtracted from each A/D sample ofthe pre-averaged PNR records. Neck rotation also often evokedchanges in eye position associated with the cervico-ocular reflex(COR). The gain and phase of PNR responses of eye-movementrelated neurons were estimated twice. One estimate of dynamicneck rotation was made without compensation of the neuron’s sen-sitivity to eye position. A second estimate was made after com-pensating the pre-averaged PNR records for the neuron’s estimat-ed sensitivity to horizontal and vertical eye position.
Dynamic neck rotation produced corresponding dynamicchanges in head position with respect to the trunk. For compara-tive purposes, an analysis was carried out to determine if the phaseof the neural response during sinusoidal PNR was related to theneuron’s sensitivity to static head-on-trunk position (kHT, seeabove). In this analysis, the response to sinusoidal PNR was as-sumed to be a linear sum of the neuron’s sensitivity to head-on-trunk position (kTS) and velocity (ST
.s).
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Based on the rotational response phase (θTS) and modulation (KTS)during sinusoidal PNR, the head position sensitivity was calculat-ed as follows:
(1)
where Ts is head-on-trunk displacement and T.s is head-on-trunk
velocity.Occasionally, non-periodic or manually generated, forced
head-on-trunk rotation (HTR) were produced. Responses evokedduring HTR were compared to a linear combination of the sinusoi-dal WBR and PNR responses. In order to account for differencesin the stimulus amplitudes and response waveforms that were pro-duced, the static position corrected sinusoidal WBR and PNR re-sponses were first decomposed into velocity (Sx
.) and acceleration(Sx) sensitivities (equation 2).
(2)
where x is either head in space (HS) during WBR or trunk in space(TS) during PNR, Kx the neuron’s firing-rate modulation, θx the re-sponse phase, and x
. and x denote the first and second derivative of x.
These sensitivity coefficients were used to compare responsesduring WBR, PNR, and HTR. During HTR, the head-on-trunk dis-placement and head movement in space were identical. Accord-ingly, the HTR responses were modeled with a linear addition ofthe static position sensitivity of the neuron and its WBR and PNRsensitivity coefficients derived from eq. 2 as follows:
(3)
where FR(t) is the neural firing rate at time t, k0 a static term relat-ed to the spontaneous firing rate with the head in the center posi-tion, kHT the neuron’s sensitivity to head-on-trunk position (HT (t))derived from the static position analysis, SH
.s and SHs are the neu-
ron’s sensitivity to head velocity and acceleration during WBR,ST
.s and STs are the neuron’s sensitivity to head-on-trunk velocity
and acceleration during PNR, H.
T(t) is the head-on-trunk velocity,and HT (t) is the head-on trunk acceleration during HTR.
The HTR responses of neurons that had eye position signalswere modeled with an equation that included an eye position coef-ficient:
(4)
where ke is the neuron’s sensitivity to horizontal eye position [re head; EH(t)] derived from the static position analysis.
Classification of neurons and categorization of vestibular and neck movement responses
Both non-eye-movement (NEM) and eye-movement related neu-rons were included in this study. Neurons were classified as NEMneurons if their firing rates were not related to eye position, didnot burst during ocular saccades, and did not respond duringsmooth pursuit of visual targets. NEM neurons have been com-monly referred to as “vestibular only” cells in the past. Eye-move-ment related neurons were further subdivided into conventionalsubclasses (Chen-Huang and McCrea 1999) based on their re-sponse during ocular saccades, smooth pursuit eye movements,and cancellation of the vestibulo-ocular reflex.
The neurons were classified as either type I or type II vestibu-lar neurons if their firing rate increased during ipsilateral or con-tralateral turntable rotation, respectively (Duensing and Schaefer1958). Similarly, neurons were classified as having a type I or typeII neck afferent response if their firing rate increased when thehead-on-trunk deviation caused by trunk rotation was ipsilateral orcontralateral to the recording site. The nomenclature is such thatneurons with type II neck responses had an increased firing rateduring contraversive head rotation. Positive and negative values infigures and tables refer to neural response gains with respect to ipsi- and contralateral rotation and to phases that led and laggedipsilateral head velocity in space during WBR and head-on-trunkvelocity during PNR. The cited variance estimates are standard errors of the mean. Phase values of neurons whose sensitivity toneck rotation was less than 0.15 sp/s/°/s were not included in thedescriptive estimates of phase.
Results
The observations reported were obtained from 80 hori-zontal canal-related vestibular-nucleus neurons. The ma-jority of the neurons (53/64 tested) were activated atmonosynaptic (73%) or disynaptic (9%) latencies fol-lowing ipsilateral electrical stimulation of the vestibularnerve (Table 1, Fig. 2A). A stereotaxic reconstruction ofthe recording tracks indicated that most neurons were lo-cated in the ventral lateral vestibular nucleus, the inferiorvestibular nucleus, and lateral parts of the medial vestib-ular nucleus. Approximately half of the neurons (45/80)had a firing behavior that was related to eye movements.The sample included 23 position-vestibular-pause (PVP)neurons, ten eye-head-velocity (EHV) neurons, and 12position-vestibular (PV) neurons. Most of them (37/45)had type I responses during passive WBR. The 35 non-
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K K TsTS TS TS= ∗ sin( ) /θS K Ts
Ts TS TS˙ cos( / ˙= ∗ θ
S K xx x x˙ cos( ) / ˙= ∗ θ
S K xx x˙ sin( ) / ˙= ∗ θ
FR t k k H t S S H t S S H tHT T Hs Ts T Hs Ts T( ) ( ) ( ) ˙ ( ) ( ) ˙ ( )˙ ˙ ˙ ˙= + ∗ + + ∗ + + ∗0
FR t k E t k H t S S H te H HT T Hs Ts T( ) ( ) ( ) ( ) ˙ ( )˙ ˙= ∗ + ∗ + + ∗
S S H tHs Ts T( ) ˙ ( )˙ ˙+ + ∗
Table 1 Summary of vestibular nucleus neurons activated follow-ing electrical stimulation of the labyrinth and their mean static eyeand head-on-trunk position sensitivity. Negative values correspondto an increased firing rate during contralateral position. The meansensitivity of each neuronal class was only computed for those
having firing rates that were significantly correlated (R2>0.5) withhead-on-trunk position1. NEM Non-eye-movement related neu-rons, PVP position-vestibular-pause neurons, EHV eye-head-ve-locity neurons, PV position-vestibular neurons
Cell type Monosynaptic Neurons sensitive Eye position Head positionvestibular act. to head position sensitivity sensitivity
n/total tested n1/total tested ke (sp/s/°) kHT (sp/s/°)
Type I, NEM 9/10 3/17 – –1.35Type II, NEM 9/17 2/18 – 1.48PVP 17/18 14/23 –3.59 –1.75EHV 9/10 3/10 –1.32 0.92PV 3/9 9/12 –1.92 –1.13Total 47/64 31/80
eye-movement related neurons (NEM neurons) werenearly evenly divided into type I and type II categoriesof rotational response. Many neurons, including bothNEM and eye-movement related neurons, were sensitiveeither to static head-on-trunk position (39%; 31/80 cellstested) or to dynamic neck rotation (78%; 46/59 cellstested). The responses of each class of cells are summa-rized in Tables 1 and 2.
Head position sensitivity of vestibular nucleus neurons
Many vestibular nucleus neurons (39%; 31/80) were sen-sitive to the position of the head on the trunk. The major-
ity of these cells (84%; 26/31) were eye-movement relat-ed neurons that were also sensitive to eye position. Thisgroup represented 58% of all eye-movement related neu-rons recorded. Figure 2 illustrates the response of a sec-ondary PVP neuron that was related to both head and eyeposition. It was monosynaptically activated followingelectrical stimulation of the vestibular nerve (Fig. 2A).Its firing rate was related to contralateral eye positionduring spontaneous eye movements, to ipsilateral headvelocity during whole body rotation (see Fig. 6A below),and it paused during saccades (black arrows below firingrate in Fig. 2B).
Figure 2B shows records of spontaneous changes ineye (re head; blue trace, EH) and head (re trunk; red
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Fig. 2A, B Neck position sig-nals in the vestibular nuclei.A Monosynaptic activation of aposition-vestibular-pause(PVP) neuron following electri-cal stimulation of the ipsilateralvestibular nerve (downward arrow). The threshold currentfor evoking a response was approximately 45 µA. The response following a supra-threshold shock is shown inred. B Firing behavior of theneuron during spontaneousgaze shifts. Records of horizon-tal eye (re head; blue, EH) andhead-on-trunk (red, HT) posi-tion, the neuron’s spike rasterand instantaneous firing rate(green histogram, FR) areshown. Two models are shown superimposed on theneuronal firing rate histogram.The first (red solid line) isbased on the neuron’s static eye and head position sensi-tivity (ke=–4.4 sp/s/°,kHT =–3.5 sp/s/°) and smoothpursuit eye velocity sensitivity(0.62 sp/s/°/s). The second(black line) is based on onlythe neuron’s eye position andeye velocity sensitivity. Shadedregions denote periods when:(a) the neck position was vol-untarily held stable and (b) theeye and head position changedin opposite directions. Greenarrows denote periods withsimilar eye positions, but dif-ferent head-on-trunk positions.Pauses during saccades are de-noted with black arrows belowthe histogram. Positive valuesrefer to movements ipsilateralto the recording site. Bin widthof instantaneous firing rate is25 ms. Responses during wholebody rotation are illustrated inFig. 6
trace, HT) position and the concomitant firing behaviorof the PVP neuron. Positive position values correspondto movements ipsilateral to the recording site. The shad-ed region on the left side of the figure shows the cell’sfiring behavior while the monkey generated a series ofspontaneous changes in eye position without significant-ly changing its head position. The black trace superim-posed on the neuron’s firing rate histogram is the pre-dicted response based on its sensitivity to contralateraleye position during fixation and eye velocity during ocu-lar pursuit when the head was restrained from moving.
The right side of Fig. 2B shows the effect of head po-sition on the neuron’s firing rate. The monkey turned itshead from an ipsilateral to a central position on the trunk(second green arrow) and then from the central to a con-tralateral position. Notice that the final eye position afterthe first gaze shift was comparable to the eye positionpreviously observed when the head was turned to the ip-silateral side (green arrows), yet the neuron’s firing rateincreased by approximately 85 sp/s.
The final gaze shift illustrated in Fig. 2B was a largecontralateral head movement that was accompanied by amovement of the eye from the center to an ipsilateral ec-centric position in the head. The neuron maintained anincreased firing rate even though the neuron’s eye posi-tion signal might have been expected to silence the cell(black line superimposed on the firing rate histogram).The red line superimposed on the neuron’s response isthe predicted firing rate based on the neuron’s sensitivityto eye movements and its estimated sensitivity to head-on-trunk position based on multiple regression analysis.
Nearly all of the neurons (24/26; 92%) that were sen-sitive to both eye and head position had sensitivities thatwere in the same direction, i.e., neurons that were sensi-tive to rightward eye-in-head position were also sensitiveto rightward head-on-trunk position. The two neurons
that had opposing eye and head position sensitivitieswere EHV neurons. Neurons were considered to carryhead position signals if changes in their firing rate werecorrelated with changes in head position (Pearsons coef-ficient, R2>0.5). A histogram of the head position sensi-tivity of 80 vestibular neurons is shown in Fig. 3A and issummarized in Table 1. Non-eye-movement related neu-rons were less likely (14%; 5/35) to have head positionsignals than eye-movement related neurons (58%;26/45). Fig. 3B is a plot of the head position sensitivity(kHT) as a function of eye position sensitivity (ke) foreye-movement related units. Note that most of the cellswere sensitive to both contralateral head and eye posi-tion, which suggests that changes in firing rate might berelated to changes in gaze position (eye+head position).A signal related to gaze position necessitates havingequivalent eye and head position sensitivities, otherwisea gaze shift produced exclusively with head movementswould produce a different change in firing rate comparedwith an equivalent gaze shift produced exclusively witheye movements. The sensitivity to eye and head positionwas rarely the same, and consequently, the firing rate ofonly a few cells changed proportionally with changes ingaze position.
Dynamic responses of vestibular neurons during passiveneck rotation
The dynamic sensitivity to passive neck rotation (PNR)was estimated for 59 vestibular nucleus neurons. In themajority of the cells (49/59), this was assayed by holdingthe head stable in space while passively rotating thetrunk and neck with the vestibular turntable (Fig. 1B).Forty five neurons were studied during passive head-on-trunk rotation (HTR) produced by rotation of the delrin
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Table 2 Summary of dynamicvestibular (top) and neck (bot-tom) responses of vestibularnucleus neurons during wholebody rotation and passive neckrotation for 0.5 Hz and 2.3 Hzstimulation. Phase values arewith respect to ipsilateral headand neck velocity. Dynamicsensitivities of eye-movementrelated neurons were estimatedfrom averaged responses aftercorrection for eye position sen-sitivity. The vestibular respons-es of EHV neurons at 0.5 Hzwere estimated from responsesduring vestibulo-ocular reflexcancellation. NEM Non-eye-movement related neurons,PVP position-vestibular-pauseneurons, EHV eye-head-velocityneurons, PV position-vestibularneurons
Vestibular
Cell type 0.5 Hz; 40°/s 2.3 Hz; 20°/s
n GHS (sp/s/°/s) θHS (°) n GHS (sp/s/°/s) θHS (°)
Type I NEM 5 0.51 –20 4 1.03 –21Type II NEM 7 0.78 174 8 0.79 168PVP 12 0.73 –23 13 1.22 –18EHV 6 0.48 –87 4 0.56 –67PV 7 0.76 –10 6 1.03 –11
Neck proprioception
Cell type 0.5 Hz; 40°/s 2.3 Hz; 20°/s
n GTS (sp/s/°/s) θTS (°) n GTS (sp/s/°/s) θTS (°)
Type I NEM 5 0.12 155 4 0.56 166Type II NEM 7 0.28 –7 8 0.47 –4PVP 13 0.29 –98 14 0.26 –150EHV 6 0.47 164 4 0.63 147PV 8 0.15 –153 7 0.22 –170
rod attached to the monkeys’ head (Fig. 1C). Some neu-rons (n=10) were studied only during HTR, and in thosecases, neck rotation sensitivity was estimated by scalarsubtraction of the whole body rotation (WBR) responsefrom the HTR response. Most of the cells tested (80%;47/59) were sensitive to neck rotation, although the dy-namic characteristics of the responses varied dependingon neuron type. Each class of vestibular neurons is de-scribed separately below. The gain and phase of the re-sponses of each cell population to neck rotation is sum-marized in Table 2 for 0.5 and 2.3 Hz stimuli.
Non-eye-movement related neurons
The cycle-averaged responses of two NEM neurons topassive sinusoidal neck rotation are illustrated in Fig. 4.The neuron illustrated in the top panels of Fig. 4A1–C1was typical of most NEM neurons. Its estimated sensitiv-ity to head velocity was 0.97 sp/s/°/s during WBR(Fig. 4A1). Its firing rate was modulated during PNR, butits sensitivity to head-on-trunk velocity (0.26 sp/s/°/s)was 73% smaller than its sensitivity to head velocity inspace during WBR. The two signals had similar dynamic
characteristics, such that the neck proprioceptive inputreduced the vestibular response during HTR (Fig. 4C1).A few neurons, like the NEM neuron illustrated inFig. 4A2–C2, were nearly as sensitive to PNR as theywere to WBR, and the neck proprioceptive input nearlyeliminated the vestibular response during HTR (Fig. 4C2).
The average neck rotation sensitivity of 25 NEM neu-rons was 0.38±0.06 sp/s/°/s re neck velocity. The sensi-tivity estimate was based on the responses recorded dur-ing PNR in 17 neurons and on the scalar subtraction ofWBR and HTR responses in eight neurons. In most cells,the sensitivity to neck rotation was smaller than the ves-tibular sensitivity during WBR (see below). The neckproprioceptive inputs to NEM neurons were nearly al-ways opposite in direction to vestibular inputs. Neuronsthat were sensitive to ipsilateral head velocity (type I)typically had neck responses that were maximal duringcontralateral head-on-trunk movements. Similarly, typeII vestibular neurons that were sensitive to contralateralhead velocity were sensitive to ipsilateral head-on-trunkmovements. Both WBR and PNR responses tended to in-crease in amplitude as the stimulus frequency increased.On average (n=12), the NEM neuronal rotational gain rehead velocity increased from 0.67±0.08 sp/s/°/s at 0.5 Hz
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Fig. 3A, B Static head positionsensitivity of vestibular nucleusneurons determined from re-sponses during periods of spon-taneous gaze shifts. A Inci-dence histograms of head-on-trunk position sensitivity for 35 non-eye-movement (NEM),23 position-vestibular-pause(PVP), 12 position-vestibular(PV), and 10 eye-head-velocity(EHV) neurons. Color indicatesneuronal class (see legend).B Static head-position sensitiv-ity (kHT) as a function of hori-zontal eye position sensitivity(ke) for eye-movement relatedneurons. The PVP neuron illus-trated in Fig. 2 is indicated(filled symbol). PV neurons occasionally had small eye po-sition sensitivities that weredifficult to resolve with themultiple regression analysis.The sensitivity sign refers to thedirection that caused an in-crease in firing rate. Positiveand negative values correspondto positions ipsilateral and con-tralateral to the recording site
to 0.87±0.14 sp/s/°/s at 2.3 Hz and the rotational gain re neck velocity increased from 0.21±0.05 to 0.50±0.07sp/s/°/s.
The HTR response of most, but not all NEM unitscould be predicted by linear addition of the neuron’sPNR and WBR responses obtained at comparable stimu-lus frequencies and amplitudes. The neuronal responsesduring HTR were compared with a model (eq. 3; dashedlines superimposed on the neuronal responses in Fig. 4C1and C2) that was the linear addition of the estimated ves-tibular and neck afferent sensitivities (eq. 2). The HTRresponse of the neuron illustrated in Fig. 4A1–C1 wasreasonably fit by the model. However, the HTR respons-es were not always entirely explained by a linear combi-nation of neck and vestibular signals. For example, theHTR response of the neuron illustrated in Fig. 4A2–C2was reasonably fit by the model at 0.5 Hz, but not during2.3 Hz HTR. The HTR stimulus illustrated in Fig. 4C2was manually produced and was not purely sinusoidal(e.g., Fig. 4C2). A frequency-analysis approach based on
the spectral properties of the manual HTR stimulus wasused in order to determine if the non-predictable re-sponse properties occurred as a consequence of distor-tions in the stimulus. The vestibular and proprioceptivetransfer functions of the neuron were linearly approxi-mated over the stimulus spectral range based on the re-sponses to 0.5 Hz and 2.3 Hz WBR and PNR. The pre-dicted vestibular and proprioceptive contribution to theHTR response was obtained by multiplying the Laplacetransform of the HTR stimulus with the correspondingtransfer function. Each contribution was inverse Laplacetransformed and linearly combined to obtain the totalpredicted time domain response based on the WBR andPNR transfer functions. This approach also did not accu-rately model the neuron’s response to the minor stimulusdistortion introduced into the manual stimulus inFig. 4C2.
Eye-movement related neurons
The firing rate of most eye-movement related neuronswas modulated during passive neck rotation. PNR usual-ly evoked a cervico-ocular reflex (COR) eye movementin the opposite direction of the head-on-trunk movement.The mean COR gain was similar for 0.5 Hz (0.40±0.04)and 2.3 Hz sinusoidal stimuli (0.33±0.05). The subtrac-tion of signals related to eye position rarely decreasedthe firing rate modulation observed during PNR. Rather,it usually produced an increase in firing rate modulationbecause most neurons that were sensitive to head-on-trunk position were sensitive to eye position in thesame direction (Fig. 3). Each of the three classes of eye-movement related neurons are discussed separately be-low.
Position-vestibular neurons. Position-vestibular (PV) neu-rons were sensitive to eye position and head velocity, but
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Fig. 4A–C Vestibular and neck proprioceptive interactions fortwo non-eye-movement related (NEM) neurons. Shown are(A1–C1) a NEM neuron with stronger vestibular input and(A2–C2) a NEM neuron with nearly equivalent vestibular and neckproprioceptive input. Two stimulus frequencies are illustrated ineach panel. Cycle-averaged responses evoked during whole bodyrotations (WBR; A1–2), passive neck rotations (PNR; B1–2), andforced head-on-trunk rotations (HTR; C1–2) are shown. Thedashed traces superimposed on the neuronal responses in C1–2 arethe predicted responses based on a linear scalar addition of theneuron’s sensitivity to head velocity during WBR and to neck ve-locity during PNR (eq. 3). The head velocity in space (H
.S, top
trace), which corresponds to the turntable velocity, is shown in A.The head velocity re trunk (HS, top trace), derived from the headposition signal, is shown in B. In C, head velocity in space isshown (top trace), which is also equivalent to head velocity retrunk. Bin widths of instantaneous firing rate is 15 ms. Number ofstimulus cycles averaged in each panel were A1: 13, 62; B1: 39,78; C1: 17, 18; A2: 24, 39; B2: 28, 36; C2: 18, 14
not to eye velocity. During PNR, many PV neurons wereweakly modulated in phase with head-on-trunk velocityin the opposite direction with respect to their vestibularsensitivity during WBR. The average neck rotation sen-sitivity of the nine PV neurons was 0.23±0.06 sp/s/°/s rehead-on-trunk velocity. Figure 5 illustrates the cycle-averaged, desaccaded responses of a PV neuron during
WBR, PNR, and HTR for two stimulus frequencies. Thegray histograms in Fig. 5 are averaged records of neuralfiring rate and the black histograms (superimposed) areaveraged records following subtraction of signals relatedto eye position. This PV neuron, like most eye-move-ment related neurons, was weakly modulated duringPNR (Fig. 5B) at both 0.5 Hz and 2.3 Hz stimulus fre-quencies. The model superimposed on the neuron’s fir-ing rate (dashed trace in Fig. 5C; eq. 4) is similar toeq. 3, but has an additional term corresponding to itseye-position sensitivity (ke=–4.4 sp/s/°). This model ac-curately predicted the response of the neuron duringHTR.
Position-vestibular-pause neurons. Position-vestibular-pause neurons were sensitive to ipsilateral head velocity,contralateral eye position, contralateral eye velocity dur-ing ocular pursuit, and they were inhibited or silencedduring saccades. As noted above, these neurons werealso sensitive to contralateral head-on-trunk position.The neuron’s response following electrical stimulation ofthe vestibular nerve and during spontaneous gaze shiftsare shown in Fig. 2. Figure 6 illustrates the average de-saccaded responses of a PVP neuron during 0.5 HzWBR, PNR, and HTR. Notice that the firing rate modu-lation was in phase with head-on-trunk position duringsinusoidal PNR even after subtraction of signals relatedto eye position (black histogram, Fig. 6B). In this cell, asin most PVP cells, subtraction of eye position signalsthat were related to the cervico-ocular reflex tended toincrease the firing rate modulation during PNR. The re-sponse of the neuron during HTR (dashed line superim-posed on neuronal firing rate in Fig. 6C) was accuratelypredicted based on eq. 4.
The average neck rotation sensitivity of the 17 PVPneurons studied during PNR was 0.29±0.05 sp/s/°/s reneck velocity at 0.5 Hz and 0.26±0.06 sp/s/°/s at 2.3 Hz.At 0.5 Hz, their firing-rate modulation was, on average,nearly in phase with contralateral head-on-trunk position(mean phase lag re ipsilateral head-on-trunk velocity:–98±16°). Their sensitivity to head-on-trunk positionduring PNR (kTS) was estimated to be –0.73±0.2 sp/s/°by decomposing the rotational response into position and velocity components based on response phase (seeMethods, eq. 1). The head-on-trunk position signal dur-
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Fig. 5A–C Vestibular and neck proprioceptive interactions in aposition vestibular neuron (PV). The neuron’s responses duringWBR (A), PNR (B) and HTR (C) are shown. Gray histograms arecycle-averaged, desaccaded responses of the neuron. Black histo-grams are the cycle-averaged responses after correcting the neu-ron’s firing rate for its static eye position sensitivity. The modelsuperimposed on the neuron’s response during HTR in C (dashedlines) is a linear addition of the neuron’s eye and head-on-trunk-position sensitivity and its dynamic responses during WBR andPNR (eq. 4). Abbreviations and bin widths are the same as inFig. 4. Number of stimulus cycles averaged in each panel wereA: 20, 46; B: 26, 67; and C: 12, 63
Fig. 6A–C Vestibular and neck proprioceptive interactions in aposition-vestibular-pause neuron (PVP). The neuron’s responsesduring WBR (A), PNR (B), and HTR (C) for 0.5 Hz stimuli areshown. The neuron was monosynaptically activated followingelectrical stimulation of the vestibular nerve and was sensitive tostatic head position during spontaneous gaze shifts (Fig. 2). Themodel shown superimposed on the neuron’s response during HTRis based on the neuron’s eye and head-on-trunk position sensitivityand its dynamic responses during WBR and PNR (eq. 4). Note, theHTR stimulus was manually produced and was not perfectly sinu-soidal. A record of head-on-trunk-position (HT) is appended to B.Response in A was obtained while the animal canceled the vestib-ulo-ocular reflex (VORc) by fixating on a table stationary target.Abbreviations and bin widths are the same as in Fig. 4. Stimuluscycles averaged in A–C were 62, 58, and 13, respectively
ing PNR was comparable, but usually smaller than thatobserved during periods of stable gaze and head positionfollowing voluntary gaze shifts (mean: –0.99±0.4 sp/s/°).Head-on-trunk position signals were less commonly ob-served during 2.3 Hz PNR, presumably because of therelatively small amplitude of the neck movement (2.8° at2.3 Hz vs. 25.4° at 0.5 Hz). A few neurons had signalsthat were in phase with head-on-trunk velocity during2.3 Hz PNR. These units contributed disproportionatelyto the average population response of PVPs at 2.3 Hzlisted in Table 2.
Eye-head-velocity neurons.Eye-head-velocity neuronswere strongly modulated during smooth pursuit eyemovements and during cancellation of the VOR (Chen-Huang and McCrea 1999). Most EHV neurons (88%;7/8) were also sensitive to passive neck rotation. Thestrength of the neck rotation signal varied from cell tocell, but on average was equal to or larger than the ves-tibular signal observed during WBR. The average neckrotation sensitivity of six EHV neurons tested during0.5 Hz PNR was 0.47±0.12 sp/s/°/s re head-on-trunk ve-locity compared with a rotational gain of 0.48±0.12sp/s/°/s re head velocity in space during WBR when themonkey canceled its VOR. At 2.3 Hz, the neck rotationsensitivity (0.63±0.19 sp/s/°/s; n=4) tended to be slightlyhigher than the rotational gain (0.56±0.12 sp/s/°/s) dur-ing WBR. In most EHV neurons (6/7), the HTR respons-
es could not be predicted from linear addition of re-sponses recorded during PNR and WBR.
Figure 7 shows the cycle-averaged responses of anEHV neuron. Its firing rate was related to ipsilateralhead velocity (H
.S) during VOR cancellation (Fig. 7A)
and to ipsilateral eye velocity (E.H) during smooth pursuit
(Fig. 7B). The neuron’s firing rate was modulated inphase with contralateral head-on-trunk velocity duringPNR (Fig. 7C) with a gain of 0.38 sp/s/°/s. PNR evoked
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Fig. 7A–D Vestibular and neck proprioceptive interactions in aneye-head-velocity neuron (EHV). The neuron’s cycle-averaged,desaccaded responses during vestibulo-ocular reflex cancellation(VORc), smooth pursuit, PNR, and HTR are illustrated in A–D. InA, C, and D, responses to 0.5 Hz stimuli are shown. In B, respons-es to 0.3 Hz stimuli are shown. The model superimposed on theneuronal firing rate in D (black dashed trace) is based on the sen-sitivity to head velocity during VOR cancellation, eye movementduring smooth pursuit, and neck movement during PNR. Abbrevi-ations and bin widths are the same as in Fig. 4. The horizontal eyevelocity re head (E
.H) is shown in each panel. Number of stimulus
cycles averaged in A–D were 10, 19, 28, and 12, respectively
Fig. 8 Head-velocity sensitivity of 59 vestibular-nucleus neuronsduring WBR plotted as a function of head-on-trunk velocity sensi-tivity during passive neck rotation. Each symbol corresponds toone neuron. Most values (n=49, black symbols) represent respons-es recorded during 2.3 Hz stimulation. The remaining neurons(n=10, gray symbols) were only recorded during 0.5 Hz stimula-tion. The neck velocity sensitivity of some neurons (n=11) wereestimated from responses during HTR (open symbols). The diago-nal line represents equivalent head and neck velocity sensitivities.The head and neck velocity signals of eye-movement related neu-rons were obtained after correction of neuronal responses for eyeposition sensitivity. Abbreviations as in Figs. 3 and 4
a cervico-ocular reflex eye movement (E.H trace in
Fig. 7C); however, the firing rate modulation duringPNR was not entirely attributable to the neuron’s sensi-tivity to eye velocity. The modulation of the neuron’s re-sponse during PNR and smooth pursuit were comparable(Fig. 7B and C), even though the eye velocity producedduring smooth pursuit was much larger than those pro-duced during the COR. Even after the PNR response wascompensated for response components related to eye ve-locity, the neuron’s estimated neck rotation sensitivity(0.31 sp/s/°/s re neck velocity) was nearly equivalent to its response during VOR cancellation (VORc; 0.43 sp/s/°/s) and smooth pursuit eye movements(0.32 sp/s/°/s re eye velocity). Figure 7D illustrates theEHV neuron response during manual HTR at approxi-mately 0.5 Hz. The neuron’s firing rate could not be pre-dicted from its sensitivity to head rotation during VORc,eye rotation during smooth pursuit, and to neck rotationduring PNR (black trace superimposed on Fig. 7D).
Comparison of neck and vestibular signals on vestibularnucleus neurons
For most vestibular nucleus neurons (76%; 45/59), neckproprioceptive signals were weaker than vestibular sig-
nals. In Fig. 8, the sensitivity of vestibular neurons tohead velocity during vestibular stimulation is plotted as afunction of their neck velocity sensitivity. Most neuronshad larger responses during 2.3 Hz rotation, and thosevalues are plotted as filled black symbols. Some cellswere tested only during 0.5 Hz rotation (gray symbols)or were estimated from responses during HTR (opensymbols). The unity line (dashed) represents equal sensi-tivity to neck rotation and angular head velocity inspace. Neurons located above the unity line were lesssensitive to neck rotation than to vestibular stimulation.Some cells (13/59) were not significantly affected bypassive neck rotation (neurons located on the ordinateaxis of Fig. 8). The neurons that exhibited the largest rel-ative sensitivity to neck rotation tended to be either EHVneurons or NEM neurons.
The dynamic properties of the neck proprioceptive in-puts to vestibular nucleus neurons during PNR are sum-marized in the polar diagrams of Fig. 9. Responses to0.5 Hz PNR are plotted in Fig. 9A, and responses to2.3 Hz PNR are shown in Fig. 9B. In each plot, the gainand phase of neural responses are represented as a vectorcomputed with respect to ipsilateral head-on-trunk veloc-ity. The distance of each point from the origin corre-sponds to the neuron’s sensitivity. The angle of the vec-
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Fig. 9A–D Dynamic character-istics of neck proprioceptive in-put to vestibular nucleus neu-rons. A, B Polar plots of theneck proprioceptive sensitivityduring 0.5 Hz and 2.3 Hz neckrotation. Response phase isplotted with respect to ipsilater-al neck velocity. Vectors locat-ed in the left hand or right handplane correspond to excitatoryresponses in phase with contra-lateral or ipsilateral neck move-ments. C, D Polar plots of theneuron’s neck proprioceptivesensitivity normalized with re-spect to its vestibular sensitivi-ty for 0.5 Hz and 2.3 Hz stimu-li. Vectors located in the lefthand or right hand plane corre-spond to neurons whose neckinputs were either antagonisticor synergistic with respect totheir vestibular response duringWBR. The circle denotes neu-rons having a sensitivity of1 sp/s/°/s (A, B) or equivalentneck proprioceptive and vestib-ular sensitivities (C, D). Thenumbers of neurons in eachplot are summarized in Table 2.Abbreviations as in Fig. 3
tor corresponds to the neuron’s response phase. A phaseof zero corresponds to a response in phase with ipsilater-al head-on-trunk velocity, and those near 90° correspondto responses in phase with ipsilateral head-on-trunk posi-tion. Note that the response gain and phase of the PNRresponses spanned a large range and was different at thetwo stimulus frequencies.
The relationship between neck proprioceptive sig-nals and vestibular signals was more orderly. Figure 9Cand D illustrate the same data normalized with respectto each neuron’s response to vestibular stimulation dur-ing WBR. The distance of each point from the origincorresponds to the relative strength of the propriocep-tive input compared with its vestibular input, with theunity circle representing equivalent proprioceptive andvestibular sensitivities. The angle of each vector withrespect to the right abscissa axis corresponds to relativephase difference between the WBR and PNR response.For example, vectors located near 180° were neuronsthat had neck proprioceptive inputs that were 180° outof phase with vestibular inputs and reduced the neu-ron’s vestibular response during HTR. Thus, in mostcases, the proprioceptive inputs tended to be antagonis-tic to vestibular inputs, particularly at 2.3 Hz (Fig. 9D).The relative strength of the neck proprioceptive inputsof some NEM neurons increased as a function of fre-quency (more neurons close to unity circle in Fig. 9D).The relative phase differences between the neck andvestibular inputs of the NEM and eye-movement relat-ed neurons were also different. NEM neurons had neckresponses that tended to be 180° out of phase with re-spect to their vestibular sensitivity (Fig. 9C, D). Eye-movement related neurons, including PVP neurons, hadneck responses that tended to be –90° out of phase withrespect to their vestibular sensitivity at 0.5 Hz, butwere closer to 180° out of phase with respect to theirvestibular response at 2.3 Hz.
Discussion
Most horizontal-canal-related vestibular neurons in thesquirrel monkey vestibular nuclei not only process ves-tibular signals related to movement of the head in space,but also signals related to the position or movement ofthe head on the trunk. The neck proprioceptive inputswere usually weaker and summed linearly with vestibu-lar or oculomotor inputs. The dynamic characteristics ofneck rotation signals were different in different classesof vestibular nucleus neurons. Most non-eye-movementrelated neurons received neck inputs that were “antago-nistic” to vestibular inputs, so that the response to pas-sive rotation of the head on the trunk was smaller than acomparable passive rotation of the whole body in space.Vestibular neurons that were sensitive to eye positionwere often also sensitive to the angular position of thehead on the trunk in the same direction. The neck posi-tion signals were usually smaller than eye position sig-nals, but both served to increase the neuron’s firing rate
during active gaze holding. In the following discussion,these results are compared with previous observations inother species, and the possible contributions of neck pro-prioceptive input to different vestibular functions areconsidered.
Previous studies of neck proprioceptive input to vestibular neurons
The types of neck movement signals observed in thisstudy in the squirrel monkey have been previously described in the cat, rabbit, and Rhesus monkey (Anastasopoulos and Mergner 1982; Boyle and Pompeiano 1980; Fredrickson et al. 1966; Fuller 1988;Kasper and Thoden 1981; Kasper et al. 1988; Pompeianoand Barnes 1971; Pompeiano et al. 1987; Wilson et al.1990). In those species, neck proprioceptive inputs alsopredominantly combined antagonistically with vestibularinputs in a linear manner (Boyle and Pompeiano 1981;Fuller 1988; Kasper and Thoden 1981; Rubin et al. 1977;Wilson et al. 1990).
Vestibulospinal neurons receive a large convergenceof neck input, which can be as strong as their vestibularinput (Boyle and Pompeiano 1981; Kasper and Thoden1981; Wilson et al. 1990). Antidromically identified ves-tibulospinal neurons in the squirrel monkey tend to fallinto two classes, non-eye-movement related neurons(Boyle 1993; McCrea et al. 1999) and neurons withproperties similar to EHV units that are sensitive tosmooth pursuit eye movements and to passive head rota-tion (Boyle 1993). In this study, the NEM neurons andEHV neurons tended to have the strongest response topassive neck rotation.
The vestibulo-oculomotor pathways are also thoughtto receive neck proprioceptive input. Stimulation of cer-vical afferents produce excitatory synaptic potentials insecondary vestibulo-ocular reflex pathways (Hikosakaand Maeda 1973; Maeda 1979; Thoden and Schmidt1979) and activate Purkinje cells in the cerebellar floccu-lus (Maeda 1979; Wilson et al. 1975a, 1975b). Althoughwe anticipated that eye-movement related units mightcarry neck proprioceptive signals, the surprising obser-vation was that the weak modulation in firing rate exhib-ited by most eye-movement related neurons during neckrotation was usually in phase with head-on-trunk posi-tion. Static head position signals have been described on secondary vestibular neurons in other species (Anastasopoulos and Mergner 1982; Fuller 1988; Khalsaet al. 1988), although their association with neurons carrying eye position signals has not been described.
Origin of neck afferent input to the vestibular nuclei
Neck proprioceptive input to vestibular neurons likelyarises from several sources. The vestibular nuclei, partic-ularly the lateral and descending vestibular nuclei andarea X, receive direct spinal inputs (Corbin and Hinsey
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1935; Edney and Porter 1986; Neuhuber and Zenker1989; Pompeiano and Brodal 1957). In addition, severalcerebellar regions that project to the vestibular nuclei(e.g., the vermis, the flocculonobular lobe, and fastigialnucleus) receive input from spinal-cerebellar pathways(Akaike 1983; Eccles et al. 1974; Furuya et al. 1975;Noda et al. 1990; Robinson et al. 1994). The role oftranscerebellar pathways in conveying proprioceptivesignals to vestibular neurons produced during headmovements and locomotion is well documented (Maeda1979; Manzoni et al. 1998; Wilson et al. 1975a). Finally,the prepositus nucleus receives input from the cervicalspinal cord, projects to the vestibular nuclei (Belknapand McCrea 1988), and contains neurons sensitive tohead-on-trunk rotation as well as eye position (Grestyand Baker 1976).
Role of neck proprioceptive signals in controlling thevestibulo-collic reflex and other vestibulo spinal reflexes
There is considerable evidence that vestibulospinal re-flexes, including in particular the vestibulo-collic reflex,are powerfully affected by neck proprioceptive sensorysignals. In cats, the majority of the neurons that projectto the cervical spinal cord are modulated by passive neckrotation (Boyle and Pompeiano 1980, 1981; Wilson et al.1990). In the squirrel monkey, both of the two classes ofvestibular cells that project to the cervical spinal cord,e.g., NEM and EHV-like cells (Boyle 1993; McCrea et al. 1999), are also modulated by passive neck rotation.Thus, it is likely that neck proprioceptive input to thevestibular nucleus plays an important role in controllingand modifying vestibulo spinal reflexes in general andvestibulo-collic reflexes in particular.
When the whole body is rotated while the head is freeto move, the vestibulo-collic reflex produces compensa-tory head movements that reduce the head velocity inspace. A consequence of these head movements is a con-comitant reduction in the vestibular drive to secondaryvestibular neurons. However, the firing rate modulationof more than half of the neurons in the vestibular nuclei,including many secondary vestibulospinal pathway neu-rons, was not proportionally reduced with decreases inhead velocity in space (Gdowski and McCrea 1999;Gdowski et al. 2000). It seems likely that neck proprio-ceptive inputs contribute to the ability of secondary ves-tibular neurons to remain sensitive to trunk velocitywhen the VCR reduces vestibular drive. This ability maybe entirely attributable to neck afferent inputs for thosefew cells whose neck velocity and vestibular sensitivitieswere comparable. In other cells whose neck afferent in-puts are comparatively weak, presumably other inputsare responsible for the ability to remain sensitive to trunkmovements. In any case, it is clear that neck propriocep-tive inputs provide a feedback signal related to the ongo-ing posture and movement of the head on the trunk tomany vestibular neurons that helps them retain their sen-sitivity to passive perturbations of the body.
Neck proprioceptive signals could be also used tomodify the VCR as a function of neck stiffness or chang-es in the load of the head. When the whole body is pas-sively rotated both neural mechanisms and biomechani-cal properties of the head and neck contribute to the pro-duction of compensatory head movements (Goldbergand Peterson 1986; Keshner and Peterson 1995; Peng et al. 1996). Although both contribute to producing com-pensatory head-on-trunk rotation, only the neural mecha-nisms are capable of modifying or finely tuning the com-pensatory movement to match a behavioral goal. Theneural control could be carried out at the level of spinalstretch reflexes or within the vestibulo-collic and othercentral reflex pathways. Neck proprioceptive inputs tosecondary vestibular neurons could function to providean estimate of the forces required to compensate forchanges in the passive inertial and mechanical propertiesof the head and neck. Both the gain and phase of the me-chanical properties of the head-neck plant increase as afunction of head movement frequency (Goldberg and Peterson 1986), so one might expect a signal that pro-vides an estimate of these parameters to exhibit similardynamic properties. Perhaps the tendency of many ves-tibular neurons, particularly NEM and EHV neurons, toexhibit an increased sensitivity during neck rotations atthe higher stimulus frequency reflected the increased de-mands placed on the VCR and neck motor plant duringhigher frequency trunk rotations.
Functional role of neck proprioceptive input to VOR pathways
Stimulation of neck proprioceptors by passive neck rota-tion evokes eye movements in many species (Baker et al.1982; Dichgans et al. 1973; Fuller 1980), including man(Barnes 1979; Kasai and Zee 1978). The central path-ways that mediate these responses are not well under-stood, but several physiological observations suggestthey may involve neurons of the VOR pathways. Abdu-cens motorneurons can be activated by stimulating theC2 dorsal root ganglion (Hikosaka and Maeda 1973;Maeda 1979) and during rotations of the body while thehead is fixed in space (Thoden and Schmidt 1979). Cir-cumstantial evidence suggests that this signal is transmit-ted to motoneurons via direct spinal inputs to secondaryVOR pathways (Maeda 1979).
A second, possibly more influential, pathway for neckproprioceptive influence on eye movements may bethrough vestibulocerebellar components of the VORpathway. The flocculus receives prominent inputs fromthe central cervical nucleus of the cervical spinal cordand from area X of the vestibular nuclei, which receiveinputs from cervical dorsal root afferents (Hirai et al.1984; Hongo et al. 1988; Takahashi et al. 1985; Wiksten1979a, 1979b). These mossy fiber inputs are capable ofmodulating the firing rate of Purkinje cells in the floccu-lus that project to brainstem VOR pathways (Wilson et al. 1975a, 1975b).
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While the evidence for neck proprioceptive inputs tocentral VOR pathways is strong, the functional role ofthese signals in the control of eye movements is still un-clear. The neck and vestibular signals on most centralneurons were usually in opposite directions. The neckproprioceptive signals related to head-on-trunk velocitythat were observed on EHV neurons, while opposite indirection with respect to the responses during VOR can-cellation, were in the same direction as the signals car-ried when monkey pursued a visual target. Thus, neckproprioceptive signals could provide a second estimateof head movement, in addition to vestibular signals,which could help compensate the VOR for loss or inade-quacy in vestibular afferent signals during rapid headmovements. In fact, neck proprioception appears to playan important role in adaptive modification of gaze stabi-lizing reflexes following labyrinthectomy or semicircularcanal plugging in animals (Baker et al. 1982; Dichganset al. 1973) and following bilateral labyrinthectomy inhumans (Bronstein and Hood 1986; Bronstein et al.1991; Kasai and Zee 1978). The vestibulocerebellummay also be involved in this mechanism since humanswith both cerebellar and vestibular atrophy fail to re-adapt reflexes (Bronstein et al. 1991).
The head position signals observed in eye-movementrelated neurons were usually in the same direction astheir eye position signals during active gaze holding.However, the two position signals combined destructive-ly during passive neck rotation since the cervico-ocularreflex eye movement was in the opposite direction of thehead-on-trunk displacement. Eye position signals on sec-ondary vestibular neurons most likely arise from the out-put of the prepositus nucleus, which represents the out-put of a central velocity position integrator circuit thattransforms central eye velocity commands into a gazeholding eye position signal. One possibility is that theprepositus computes a static eye position signal by inte-grating the difference between an estimate of gaze veloc-ity and an estimate of head-on-trunk velocity. This mightexplain why the prepositus receives central commandsfrom short lead inhibitory burst neurons (Cullen and Guitton 1996; Strassman et al. 1986) that are in gaze co-ordinates, as well as neck reafferent signals from the cer-vical spinal cord (Belknap and McCrea 1988; Gresty andBaker 1976). The observation of neck position signals onsome, but not all VOR neurons during active gaze shiftsmay represent the imperfect construction of an eye posi-tion signal from gaze velocity and neck reafferent infor-mation. When the body is passively turned around a sta-ble head, neck proprioceptive input is generated in theabsence of gaze motor commands. In this extraordinarycircumstance, the output of the prepositus might repres-ent a neural integration of unopposed neck reafferent in-put, which is then reflected in the response properties ofVOR neurons.
Summary
Neck proprioceptive signals are commonly observed inthe primate vestibular nucleus. Their strength and dy-namic characteristics vary in different types of vestibularnucleus neurons. It seems likely that these inputs play animportant role in shaping the output of central vestibularpathways contributing to the control of gaze, posture,and self motion perception.
Acknowledgement This work was supported by NIH grants R01-EY08-041 and DC02072.
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