Efferent-mediated responses in vestibular nerve afferents of the alert macaque

Abstract

The peripheral vestibular organs have long been known to receive a bilateral efferent innervation from the brain stem. However, the functional role of the efferent vestibular system has remained elusive. In this study, we investigated efferent-mediated responses in vestibular afferents of alert behaving primates (macaque monkey). We found that efferent-mediated rotational responses could be obtained from vestibular nerve fibers innervating the semicircular canals after conventional afferent responses were nulled by placing the corresponding canal plane orthogonal to the plane of motion. Responses were type III, i.e., excitatory for rotational velocity trapezoids (peak velocity, 320 degrees/s) in both directions of rotation, consistent with those previously reported in the decerebrate chinchilla. Responses consisted of both fast and slow components and were larger in irregular (approximately 10 spikes/s) than in regular afferents (approximately 2 spikes/s). Following unilateral labyrinthectomy (UL) on the side opposite the recording site, similar responses were obtained. To confirm the vestibular source of the efferent-mediated responses, the ipsilateral horizontal and posterior canals were plugged following the UL. Responses to high-velocity rotations were drastically reduced when the superior canal (SC), the only intact canal, was in its null position, compared with when the SC was pitched 50 degrees upward from the null position. Our findings show that vestibular afferents in alert primates show efferent-mediated responses that are related to the discharge regularity of the afferent, are of vestibular origin, and can be the result of both afferent excitation and inhibition.

FIG. 1.

Finding the null plane of the vertical canals. A: response of an afferent to manual pitch rotations. As it is excited by downward pitches, the unit is a superior canal (SC) unit. B: response of the same SC unit during rotations about an earth-vertical axis after the animal is placed in 1 of 3 pitch positions. The unit is excited by (a) clockwise (CW) rotations at 0° pitch, defined as the stereotaxic plane being earth horizontal. The unit was (b) nulled near 20° nose-down (ND), and (c) excited by counterclockwise (CCW) rotations at 30° nose-down. In all figures, rotation direction is as viewed from above. C: calculating the null angle. The normalized sensitivity, calculated relative to that at 0° pitch, is plotted as a function of pitch angle. A linear regression passes through 0 sensitivity at a pitch angle of 21° ND, which is considered the null position. Letters a, b, and c correspond in B and C.

FIG. 2.

Efferent-mediated responses in the control (CNTL) condition for an irregular (left) and a regular (right) vertical canal (VC) unit. The animal was in the VC-null position and rotated using the velocity trapezoid stimulus (top traces). Average responses based on >10 trials are shown for CW and CCW rotations as viewed from above. Traces for both directions are the average of the CW and CCW averages. The horizontal line marks the resting discharge of the afferent. The efferent-mediated response is excitatory and symmetric for both directions of rotation (i.e., type III). The response of the irregular unit is larger and more rapidly developing than that of the regular unit. Note the postrotational excitatory responses in both units. For a conventional afferent response, CW and CCW responses would be in opposite directions and the postrotatory would be in the opposite direction from the per-rotatory response.

FIG. 3.

Efferent-mediated population responses in the control (CNTL) condition averaged for irregular (left) and regular (right) VC [including SC and posterior canal (PC)] units. The animal was in the VC-null position (inset) and rotated using the velocity trapezoid stimulus (top traces). Population responses for CW and CCW rotations and for both directions, based on averaging the average traces, such as seen in Fig. 2 for individual units are shown. The horizontal lines mark the average resting discharge of the afferents. The population responses in the CNTL condition were similar to those shown for the individual afferents in Fig. 2. See Table 1 for sample sizes.

FIG. 4.

Efferent-mediated responses following unilateral labyrinthectomy (UL) on right side, i.e., contralateral to the recording side, averaged for irregular (left) and regular (right) VC units. See Table 1 for sample sizes. A: the animal was in the VC-null position (inset) and rotated using the velocity trapezoid stimulus (top traces). In this position, only the horizontal canal (HC) on the intact side should be responsive. Population responses are shown for CW and CCW rotations, as well as the average population responses for rotations in both directions (bottom traces). The horizontal lines mark the average resting discharge of the afferents. Rotations that were excitatory (CCW) or inhibitory (CW) for the HC both resulted in excitatory efferent-mediated response in the VC units. The dynamics and magnitudes of the responses were similar to the CNTL condition for either irregular and regular units [compare uncolored (CNTL) and colored (UL) traces].

FIG. 5.

Following contralateral UL followed by unilateral plugging (PL) of the ipsilateral HC and PC, only the ipsilateral SC is responsive to roations. By placing the animal in the SC-null position, canal signals should be minimized in UL + PC animals compared with UL animals in which the ipsilateral HC was nearly maximally sensitive. Population responses in the SC-null position (cartoon) averaged for both rotation directions in the UL + PL condition are compared with the responses in the UL condition. See Table 1 for sample sizes. As expected, efferent-mediated responses were greatly reduced in SC or non-SC (HC + PC) units in UL + PL animals (colored traces) compared with SC units in CNTL animals (uncolored traces). The horizontal lines mark the average resting discharge of the afferents. In the UL + PL condition, only the ipsilateral SC was potentially responsive to rotations; because this canal was nulled, no vestibular signals were available. The large reduction in UL + PL compared with UL animals is consistent with vestibular signals making a large contribution to efferent-mediated responses.

FIG. 6.

Comparisons of efferent-mediated, type III responses under various conditions. Each point represents the average response for CW and CCW rotations in individual units. A: responses vs. normalized coefficient of variation or CV* for SC units following UL in comparison to SC units following UL + PL. These responses were recorded with the animal pitched to 20° ND (SC null) condition. Straight lines are linear regressions between type III response magnitudes and log (CV*) for the 2 preparations. B: responses in non-SC units in UL + PL animals are compared in 20° ND (SC null) (ordinate) and 30° NU (abscissa) positions. Straight line is linear regression through the origin. C: responses vs. normalized coefficient of variation (CV*) for VC units in CNTL (red triangles) and UL (green squares) animals pitched to 20° ND and for non-SC units in UL + PL animals pitched to 30° NU (blue diamonds). Straight lines for the 3 groups determined from an ANCOVA that compared response magnitudes with log (CV*) as the covariate. Two points (arrows) had to be left out of ANCOVA to preserve the homogeneity of residual variances among the 3 groups. Response magnitude as a function of log (CV*) was similar for the 3 groups.

FIG. 7.

Schematic of the connectivity of the central efferent vestibular pathways. Type I cells in the vestibular nuclei (VN) are excited by ipsilateral rotations (e.g., rightward rotations shown by curved arrows) and are inhibited by contralateral rotations (response direction denoted by small arrows). Type II neurons in each VN make inhibitory synapses with type I neurons on the same side (dashed line). Following UL, type I neurons on the ipsilesional side are modulated by ipsilesional rotations, as a result of disinhibition through ipsilesional type II cells. Signals from type I cells on the 2 sides can lead to excitatory responses from efferent cells during rotations in both directions, thus resulting in type III responses in the periphery.