Convergence of vestibular and neck proprioceptive sensory signals in the cerebellar interpositus

Abstract

The cerebellar interpositus nucleus (IN) contributes to controlling voluntary limb movements. We hypothesized that the vestibular signals within the IN might be transformed into coordinates describing the body's movement, appropriate for controlling limb movement. We tested this hypothesis by recording from IN neurons in alert squirrel monkeys during vestibular and proprioceptive stimulation produced during (1) yaw head-on-trunk rotation about the C1-C2 axis while in an orthograde posture and (2) lateral side-to-side flexion about the C6-T3 axis while in a pronograde posture. Neurons (44/67) were sensitive to vestibular stimulation (23/44 to rotation and translation, 14/44 to rotation only, 7/44 to translation only). Most neurons responded during contralateral movement. Neurons (29/44) had proprioceptive responses; the majority (21/29) were activated during neck rotation and lateral flexion. In all 29 neurons with convergent vestibular and neck proprioceptive input those inputs functionally canceled each other during all combined sensory stimulation, whether in the orthograde or pronograde posture. These results suggest that two distinct populations of IN neurons exist, each of which has vestibular sensitivity. One population carries vestibular signals that describe the head's movement in space as is traditional for vestibular signals without proprioceptive signals. A second population of neurons demonstrated precise matching of vestibular and proprioceptive signals, even for complicated stimuli, which activated the semicircular canals and otolith organs and involved both rotation and flexion in the spine. Such neurons code body (not head) motion in space, which may be the appropriate platform for controlling limb movements.

Figure 1.

A, Schematic illustration of postural manipulations for the on-axis and off-axis rotation conditions. In the on-axis condition, subjects were aligned with the vertical axis of the rotational turntable and motion of the head occurred about the C1–C2 vertebral axis. In the off-axis condition, the head was displaced forward (r = 8 cm) so that rotational movements occurred by producing lateral flexion at lower vertebral levels (C6–T3). B, Schematic illustration of the on-axis experimental paradigms that were used including WBT using the sled (see arrows denoting movement), WBR using the turntable, PNR using the turntable to rotate the body while the head was restrained to the ceiling, and HTR using the ceiling motor to rotate the head while the body was held stationary in space. Shown are as follows: (a) ceiling motor, (b) fixation point to connect the earth-vertical axis of rotation to the ceiling motor or ceiling, (c) vertical rod defining earth-vertical rotational axis, (d) fixation point on the trunk, (e) turntable, (f) sled, and (g) fixation point to connect rotational axis to head. C, Schematic illustration of the off-axis experimental paradigms that were used including EVA-WBR (A, top view illustration denotes the difference compared with WBR), EVA-PNR, and EVA-HTR.

Figure 2.

A, Histological coronal section (AP = 6.0 mm) through the right cerebellum and brainstem regions including the interpositus and vestibular nuclei. Three electrode penetrations are evident from gliotic scars in the anterior interpositus. B, Schematic representation of the coronal section in A. Lines correspond to electrode trajectories. Symbols denote approximate locations of all neurons that were sensitive to vestibular stimulation recorded in all three animals using recording maps from each of the animals that were registered with respect to each other, initially based upon the stereotaxic placement of electrodes and later refined based upon physiological recording from bordering structures. C, Patterns of evoked activity for two neurons (identified as 1 and 2 in B) recorded along a single track (dashed line) during ipsilateral vestibular labyrinth (left) and contralateral ventral thalamic (right) stimulation. The two neurons recorded along this track were located in (1) ventral IN and (2) ventral medial vestibular nuclei. The first IN unit was antidromically activated (1t, 150 μA) by thalamic stimulation. The top trace shows an example of a collision where a spontaneously generated action potential (a) resulted in the absence of an electrically evoked response during thalamic stimulation (d). The same IN neuron was not activated by labyrinth stimulation (1v, 150 μA). The second unit, recorded in the medial vestibular nucleus, was orthodromically activated by ipsilateral vestibular labyrinth stimulation (2v, 300 μA) and not by contralateral thalamic stimulation (2t, 500 μA). MVN, medial vestibular nucleus; IVN, inferior vestibular nucleus; PH, nucleus prepositus hypoglossi; NTS, nucleus of the solitary tract; ABD, abducens nucleus; SIX, nucleus salivatorius inferior; NSV, nucleus tractus spinalis; *, field potential in IN with contralateral VL stimulation.

Figure 3.

A, Vestibular responses of three IN neurons sensitive to sinusoidal WBR (2 Hz, ±10°/s) or side-to-side WBT (2 Hz, ± 0.05 G). Each row corresponds to a different type of unit including a canal-only unit that responded only during WBR and not during side-to-side WBT, an otolith-only unit that responded during side-to-side WBT but not during WBR, and a canal–otolith unit that responded during both WBR and side-to-side WBT. Traces shown include: head velocity (Ḣ), head acceleration (Ḧ), and unit discharge rate (gray fill). Schematic illustrations shown above each figure correspond to the paradigm that was used. Fits for estimating vestibular sensitivities are shown superimposed on the unit's discharge rate (see Materials and Methods). All recordings were from animal B. All averages included 30 stimulus cycles. All three of these example neurons also have neck sensitivity and are discussed in later figures. B, Polar plots summarizing the vestibular response properties of IN neurons. Left, Gain and phase response properties of IN neurons during 2 Hz WBR for canal-only (n = 14) and canal–otolith (n = 23) neurons. Type I (right-hand plane, filled symbols) and type II (left-hand plane, open symbols) are shown. Gains and phases were computed with respect to rotational velocity. Right, Gain and phase response properties of IN neurons during 2 Hz EVA-WBR as a function of unit type (otolith-only, n = 7; canal–otolith, n = 23). Gains and phases were computed with respect to translational acceleration.

Figure 4.

A, Responses during eccentric off-axis rotations (EVA-WBR). The three neurons illustrated are the same as those in Figure 3. Responses are shown for EVA-WBR (2 Hz, ±10°/s) while the head was located 8 cm in front of the earth-vertical axis. Each row corresponds to a different type of unit including a canal-only neuron, an otolith-only neuron, and a canal–otolith neuron. Traces shown include head velocity (Ḣ), head acceleration (Ḧ), and unit discharge rate (gray fill). Schematic illustration at the top shows the paradigm that was used. Models superimposed on each unit's response (dashed lines) are a linear combination of the WBR and WBT response sensitivities illustrated in Figure 3 (see Materials and Methods). All recordings were from animal B. All averages included 30 stimulus cycles. B, Linearity of responses during eccentric off-axis rotations (EVA-WBR). Top, Estimated gain from a linear model representing a combination of the WBR and WBT response sensitivities as a function of the gain determined by regressively fitting the neural response. The superimposed line is a linear fit (model gain = 1.04*g_eva-wbr− 0.041sp/s/°/s; R² = 0.993). Bottom, Estimated response phase from the linear model as a function of the response phase determined by regressively fitting the neural response. The superimposed line is a linear fit (model phase = 0.96*θ_eva-wbr + 2.9°; R² = 0.984). Thirty-two neurons are shown including: 9 canal-only, 4 otolith-only, and 19 canal–otolith neurons (see legend). The filled symbols are the three neurons illustrated in Figure 3.

Figure 5.

A, Typical responses of IN neurons during on-axis neck rotations about the C1–C2 axis (left, PNR) and off-axis neck flexion about the C6–T3 axis (right, EVA-PNR). Shown are the responses during 2 Hz rotations (±10°/s) for a canal-only (top), otolith-only (middle), and canal–otolith neuron (bottom). Traces shown include neck angular velocity (solid trace) and unit discharge rate (histogram). Fits for estimating the unit's gain and phase are shown superimposed on the unit's discharge rate. The neurons illustrated here are the same as in Figure 3. B, Summary of the IN neuron response properties during axial PNRs and lateral neck flexion (EVA-PNR). Left, A polar plot summarizing the gain and phase characteristics of neuron responses during PNR as a function of unit type. Right, A polar plot summarizing the gain and phase characteristics of neuron responses during EVA-PNR as a function of unit type. Filled (ipsilateral sensitive) and open (contralateral sensitive) symbols in all plots denote the unit's vestibular sensitivity.

Figure 6.

Comparison of neck proprioceptive and vestibular sensitivities. A, Top, Gain during PNR as a function of the gain during WBR. Bottom, Relative phase during PNR as a function of the relative phase during WBR. Relative phase was computed by subtracting 180° from both the WBR and PNR response phase if the WBR response phase was >180°. In both graphs, linear fits are shown superimposed upon the population of IN neurons having both WBR and PNR responses with significant gains (>0.1 sp/s/°/s). Linear fits: Top, g_pnr = 0.99*g_wbr + 0.001, R² = 0.85 and bottom, θ_pnr = 0.95*θ_wbr + 2.54, R² = 0.95. B, Top, Gain during EVA-PNR as a function of the gain during EVA-WBR. Bottom, Relative phase during EVA-PNR as a function of the relative phase during EVA-WBR. In both right-side graphs, linear fits are shown superimposed upon the population of IN neurons having both EVA-WBR and EVA-PNR responses with significant gains (>0.1 sp/s/°/s). Linear fits: top, g_eva-pnr = 1.04*g_eva-wbr + 0.01, R² = 0.92 and bottom, θ_eva-pnr = 0.92*θ_eva-wbr + 3.55, R² = 0.93.

Figure 7.

A, Responses of three types of neurons during HTRs (2 Hz, ±10°/s) about the C1–C2 axis including a canal-only unit, a canal–otolith unit, and an otolith-only unit. B, Responses of three types of neurons during EVA-HTR (2 Hz, ±10°/s) that produced lateral flexion of the neck including a canal-only unit, a canal–otolith unit, and an otolith-only unit. The neurons illustrated here are the same as in Figure 3. C, Top, The relative gain during HTRs (HTR gain/WBR gain) as a function of the relative strength of on-axis rotational proprioceptive signals (1 − [PNR gain/WBR gain]). Bottom, The relative gain during eccentric HTRs (EVA-HTR gain/EVA-WBR gain) as a function of the relative strength of on-axis rotational proprioceptive signals (1 − [EVA-PNR gain/EVA-WBR gain]). Each type of neuron is identified with different symbols (see legend).