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Vestibular Signals in the Parasolitary Nucleus
N. H. BARMACK AND V. YAKHNITSA
Neurological Sciences Institute, Oregon Health Sciences University, Portland, Oregon 97201
INTRODUCTION
The anatomical entity termed the Parasolitary nucleus (Psol)
derives its name primarily because of its proximity to the
nucleus solitarius and tractus solitarius. It is located dorsal and
lateral to these structures. It extends rostrocaudally for about 2
mm and in its most rostral extent lies wedged between the
medial and descending vestibular nuclei (MVN and DVN).
Rather than being directly a part of a baroceptive regulation,
the Psol is really the most caudal subdivision of the vestibular
complex.
The Psol consists of a compact cluster of 2,300 smalldiameter neurons (5–7 ␮m diam) extending from the nucleus
solitarius to the surface of the fourth ventricle (Barmack et al.
1998). In the rabbit, the Psol is identifiable using either cytoarchitectonic or immunohistochemical criteria (Fig. 1B). All
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Psol neurons are labeled by an antiserum to glutamic acid
decarboxylase (GAD; Fig. 1A), the synthetic enzyme for the
neurotransmitter gamma amino butyric acid (GABA) (Barmack et al. 1998).
Vestibular primary afferents project to Psol, demonstrated
by the distribution of neuronal degeneration following lesion of
the vestibular nerve (Korte 1979). This projection is also
revealed by the orthograde transport of the C-fragment of
tetanus toxin (TTC) into vestibular primary afferents terminals
in the Psol following injection of TTC into the membranous
labyrinth through the oval window (Barmack, unpublished
observations).
The Psol receives secondary vestibular afferent projections from neurons in the DVN and MVN (Ruggiero et al.
1996) and a bilateral descending projection from the fastigial nuclei that is shared with other vestibular nuclei (Walberg et al. 1962a,b). The Psol also receives projections from
cerebellar Purkinje cells located in the ipsilateral uvulanodulus (N. H. Barmack, Z.-Y. Qian, and J. Yoshimura,
unpublished data). Unlike the nucleus solitarius, the Psol
receives no sensory fibers from cranial nerves VII, IX, and
X (Allen 1923; Altschuler et al. 1989).
Evidence from both orthograde and retrograde tracer
studies indicates that the Psol is the source of the GABAergic projections to the ␤-nucleus and dorsomedial cell column (dmcc) of the inferior olive and the nucleus reticularis
gigantocellularis (NRGc) (Barmack et al. 1998; Fagerson
and Barmack 1995; Kaufman et al. 1996) (Fig. 1). Singleneuron recordings from the ␤-nucleus, dmcc, and NRGc
indicate that neurons in these nuclei respond to vestibular
stimulation with increases during contralateral static and
dynamic roll-tilt about the longitudinal axis (Barmack 1996;
Barmack et al. 1993a; Fagerson and Barmack 1995). The
␤-nucleus and dmcc send climbing fiber projections to the
contralateral uvula-nodulus where vestibular-related climbing fiber responses are mapped onto sagittal strips (Barmack
and Shojaku 1995; Fushiki and Barmack 1997). These strips
encode ipsilateral static and dynamic roll-tilt. In the uvulanodulus, as in the ␤-nucleus and dmcc, no modulation of
activity is evoked by vestibular stimulation in the plane of
the horizontal semicircular canals.
Since the anatomical evidence indicates that the Psol is
involved in the processing of vestibular information, in this
experiment we have examined how Psol neurons encode natural vestibular stimulation. We have sought answers to three
questions: are Psol neurons modulated by physiological vestibular stimulation, do signals from all vestibular end organs
drive Psol neurons, and do Psol neurons receive convergent
optokinetic signals? We answered these questions by using the
0022-3077/00 $5.00 Copyright © 2000 The American Physiological Society
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Barmack, N. H. and V. Yakhnitsa. Vestibular signals in the parasolitary nucleus. J Neurophysiol 83: 3559 –3569, 2000. Vestibular
primary afferents project to secondary vestibular neurons located in
the vestibular complex. Vestibular primary afferents also project to
the uvula-nodulus of the cerebellum where they terminate on granule
cells. In this report we describe the physiological properties of neurons in a “new” vestibular nucleus, the parasolitary nucleus (Psol).
This nucleus consists of 2,300 GABAergic neurons that project onto
the ipsilateral inferior olive (␤-nucleus and dorsomedial cell column)
as well as the nucleus reticularis gigantocellularis. These olivary
neurons are the exclusive source of vestibularly modulated climbing
fiber inputs to the cerebellum. We recorded the activity of Psol
neurons during natural vestibular stimulation in anesthetized rabbits.
The rabbits were placed in a three-axis rate table at the center of a
large sphere, permitting vestibular and optokinetic stimulation. We
recorded from 74 neurons in the Psol and from 23 neurons in the
regions bordering Psol. The activity of 72/74 Psol neurons and 4/23
non-Psol neurons was modulated by vestibular stimulation in either
the pitch or roll planes but not the horizontal plane. Psol neurons
responded in phase with ipsilateral side-down head position or velocity during sinusoidal stimulation. Approximately 80% of the recorded
Psol neurons responded to static roll-tilt. The optimal response planes
of evoked vestibular responses were inferred from measurement of
null planes. Optimal response planes usually were aligned with the
anatomical orientation of one of the two ipsilateral vertical semicircular canals. The frequency dependence of null plane measurements
indicated a convergence of vestibular information from otoliths and
semicircular canals. None of the recorded neurons evinced optokinetic
sensitivity. These results are consistent with the view that Psol neurons provide the vestibular signals to the inferior olive that eventually
reached the cerebellum in the form of modulated climbing fiber
discharges. These signals provide information about spatial orientation about the longitudinal axis.
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technique of extracellular microelectrode recording from Psol
neurons in anesthetized rabbits.
METHODS
Anesthesia and surgery
Twenty pigmented rabbits (weight 0.8 –1.7 kg) were anesthetized
intravenously with ␣-chloralose (50 mg/kg) and urethan (500 mg/kg)
or intramuscularly with ketamine hydrochloride (50 mg/kg), xylazine
(6 mg/kg), and acepromazine maleate (1.2 mg/kg). Rectal temperature
was monitored and maintained at 37°C. The adequacy of anesthesia
was evaluated using the corneal reflex as an indicator.
In a preparatory operation, a dental acrylic plug was formed to the
calvarium of each rabbit. This plug held two inverted stainless steel
screws (8 –32) to the dorsal surface of the calvarium. Five smaller
stainless steel screws (2–56) were screwed into the calvarium and
helped to anchor the acrylic plug. The larger inverted screws mated
with a metal rod that was used to maintain the head rigidly fixed in the
center of a vestibular rate table.
Glutamic acid decarboxylase immunocytochemistry
Two rabbits were deeply anesthetized (as described in the preceding text) and perfused transcardially with physiological saline followed by a fixative consisting of 4% formaldehyde, 0.2% zinc salicylate, and 0.9% NaCl, pH 6.5 (Mugnaini and Dahl 1983). The brain
stems rostral to the obex and caudal to the dorsal cochlear nuclei were
removed and cryo-protected in graded sucrose in saline prior to being
frozen and sectioned on a cryostat at 30 ␮m. The sections were
processed for glutamic acid decarboxylase (GAD) immunocytochem-
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FIG. 1. Parasolitary nucleus (Psol) topography in the rabbit. A, 1–3: transverse sections immunolabeled with antiserum to
glutamic acid decarboxylase (GAD). Sections are spaced ⬃500 ␮m apart, from rostral (A1 to caudal A3). B, 1–3: histology of Psol
neurons identified with Klüver-Barrera stain. MVN, medial vestibular nucleus; Nsol, nucleus solitarius; sol, tractus solitarius.
Calibration bar in B3 applies to all panels.
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istry as previously described using a double-peroxidase–anti-peroxidase protocol (Barmack et al. 1998).
Vestibular stimulation
The head of the rabbit was held rigidly in the center of rotation of
a three-axis vestibular rate table with the plane of the horizontal
semicircular canals maintained in the earth horizontal plane. The body
of the rabbit was encased in foam rubber and fixed with elastic straps
to a plastic tube aligned with the longitudinal axis of the rate table.
The rate table was sinusoidally oscillated about its vertical axis (yaw),
about its longitudinal axis (roll), or about its interaural axis (pitch)
(⫾10°, 0.005– 0.800 Hz). During vestibular stimulation the vision of
the rabbit was occluded by hemispherical ping pong balls.
Static vestibular sensitivity
Static vestibular stimulation was used to test for the otolithic origin
of vestibularly evoked discharges. The rabbit was tilted 5–10° about
the longitudinal axis. After an adaptation period of 20 –30 s, the
average discharge frequency was measured for the next 20 –30 s. The
rabbit was then tilted in the opposite direction. A difference in mean
discharge frequency of 20%, evoked for roll tilts in the two opposite
directions, indicated sensitivity to linear acceleration. Based on the
predominant mediolateral polarization vector of hair cells within the
utricular maculae, as opposed to the predominant ventral-dorsal polarization vectors for hair cells within the saccular maculae (Fernandez and Goldberg 1976), we presume that a static roll stimulus evoked
activity originating primarily from utricular hair cells.
Vestibular null plane measurement
A “null technique” was used to characterize the peripheral origins
of the vestibular signals that modulated the activity of Psol neurons.
While the rabbit was rotated about the longitudinal axis of the rate
table, the angle of the rabbit’s head was changed about the vertical
axis until a minimum in stimulus-modulated neuronal activity was
detected (null plane). On either side of this null plane, the phase of
modulated activity was shifted with respect to the vestibular forcing
function by 180°. For each tested neuron, the null plane characterized
the polarization vector of the hair cells of particular end organs that
contributed to the modulated response. The “optimal plane,” the plane
of maximal neuronal modulation was assumed to be orthogonal to the
null plane (Fushiki and Barmack 1997).
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FIG. 2. Activity of a Psol neuron evoked by sinusoidal roll vestibular stimulation. A: vestibular stimulation about the longitudinal axis evoked maximal
modulation of neuronal activity when the left posterior
semicircular canal was orthogonal to the axis of rotation. The head of the rabbit was oriented 45° clockwise
(CW) with respect to the longitudinal axis. Neuronal
activity increased during rotation onto the left side and
decreased during rotation onto the right side. The sign
wave at the bottom of the figure indicates rotation
about the longitudinal axis. An upward deflection indicates rotation onto the left side. B: when the head of
the rabbit was oriented 39° counterclockwise (CCW)
with respect to the longitudinal axis, the activity of the
Psol neuron was not modulated by sinusoidal roll. In
this “null plane,” the left posterior semicircular canal
was colinear to the axis of rotation. C: when the head
of the rabbit was oriented 48° CCW with respect to the
longitudinal axis (about 9° past the null plane), modulation of neuronal activity again appeared but with a
phase shift of 180° with respect to the sinusoidal stimulus. The location of the recorded neuron within the
Psol is illustrated in D. Amb, nucleus ambiguus; Cu,
cuneate nucleus; dmcc, dorsomedial cell column of the
inferior olive; icp, inferior cerebellar peduncle; LPC,
RAC, left posterior and right anterior semicircular canals; DVN, descending vestibular nuclei; NPH, nucleus prepositus hypoglossi; NRGc, nucleus reticularis
gigantocellularis; SpV, spinal trigeminal nucleus.
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Optokinetic stimulation
The rate table was located at the center of a large sphere (1.45 m
diam). A 120° segment was cut out of the sphere to allow convenient
access to the animal. Nonetheless it was possible to orient the rabbit
so that the visual field of a single eye was completely encompassed by
the interior surface of the sphere. A perforated aluminum globe (4 cm
diam), with a 50-W tungsten filament microscope bulb on the inside,
was positioned just over the head of the rabbit. The globe was
mounted on a small pen motor. Movement of this globe was controlled by voltage ramps to the pen motor. The globe-pen motor could
be aligned with any axis to create movement about that axis. The
optokinetic sensitivity of Psol neurons was tested for stimulation
about the vertical, longitudinal, and oblique axes.
Microelectrode recording
The Psol was approached by reflecting the muscles overlying the
cisterna magna and enlarging the dorsal aspect of the foramen magnum. The dura mater was carefully removed exposing the dorsal
surface of the brain stem and folia 9c of the cerebellum. The meningeal attachments of the cerebellum were carefully cut, allowing the
cerebellum to retract 1–2 mm rostrally. A hydraulic microdrive,
attached to the head-restraint bar, advanced tungsten microelectrodes
toward a region of the dorsal brain stem just caudal to the medial
vestibular nucleus about 1.8 mm lateral to the midline. The micro-
electrodes had an extended taper so that the diameter of the final 4 mm
was ⬍50 ␮m. The tip impedance was ⬃4 M⍀.
Action potentials were discriminated with a window-slope discriminator-Schmitt trigger. Discriminated action potentials were analyzed
by computer using Spike 2 software (Cambridge Electronic Design).
Evoked single-unit activity was displayed on-line as a peristimulus
histogram. Peristimulus histograms were constructed using different
numbers of stimulus cycles at different stimulus frequencies. During
data acquisition, each stimulus cycle was divided into 180 bins.
Interspike intervals for spike occurrences were stored in these bins.
The reciprocal of these interspike intervals, spike frequency, was
averaged for the number of spike occurrences in each bin.
Histological verification of recording sites
The location of each neuron from which recordings were obtained
was marked electrolytically (⫺8 ␮A, 30 s). At the conclusion of the
experiment each rabbit was deeply anesthetized and perfused transcardially with 0.9% saline, followed by 10% paraformaldehyde. The
brain was removed and cryoprotected with 10, 20, and 30% sucrose in
0.1 M PBS, pH 7.2. The brain stem was blocked sagittally, mounted
onto cork with OCT compound, and frozen in isopentane cooled with
dry ice. Sagittal frozen sections (35 ␮m) were cut and collected in
cold 0.1 M PBS and mounted serially. The location of each recorded
neuron was reconstructed from the locations of the marking lesions.
These locations were analyzed in transverse histological sections and
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FIG. 3. Responses of a Psol neuron to static roll. Step-roll stimulation was used to characterize the otolithic sensitivity of Psol
neurons. A: this neuron, recorded from the left Psol increased its rate of discharge when the rabbit was rolled onto its left side. The
step response at the bottom of the figure indicates step-roll about the longitudinal axis. An upward deflection indicates step-roll onto
the left side. B: cartoon indicates the optimal response plane for the Psol neuron whose responses are shown in A. C: the
peristimulus histogram for this neuron illustrates 2 complete cycles of vestibular step roll-tilt. D: this neuron was located in the Psol
⬃500 ␮m rostral to its caudal pole. The rectangle demarcates the area of the photomicrograph in E. 2, microlesion that marked
the location of the neuron. X, dorsomotor nucleus of the vagus.
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two discharge rates reflects the stimulus-driven activity of
many otherwise quiescent Psol neurons.
We measured the null plane of 47/74 Psol neurons from
which we recorded and inferred the optimal response planes
from these null planes. During sinusoidal vestibular stimulation about the longitudinal axis, the orientation of the head of
the rabbit was systematically changed until a minimum in the
evoked modulation of Psol activity was reached (Fig. 2B). On
either side of the null plane the modulation of activity was
phase shifted by 180° (Fig. 2, A and C). The optimal plane for
the neuron illustrated in Fig. 2 aligned with the ipsilateral
posterior and contralateral anterior semicircular canals (Fig.
2A).
Absence of Psol responses to horizontal vestibular
stimulation
Absence of optokinetic modulation of Psol neuronal activity
The activity of none of the neurons localized to Psol could
be modulated by optokinetic stimulation. The absence of a
modulated optokinetic response was not dependent on the
particular alignment of the optokinetic stimulation. There was
no modulation of Psol activity when the optokinetic stimulation axis was coaxial as well as orthogonal to the optimal axis
of vestibular stimulation.
FIG. 4. Influence of stimulus frequency on a cell with static vestibular
sensitivity. A: a peristimulus histogram for a neuron recorded in the left Psol
during static roll-tilt stimulation indicates sensitivity to static tilt. B: the
figurine indicates that the optimal plane for this neuron was 36° CCW to the
longitudinal axis. C: 1, location of the neuron in the rostral Psol. D: peristimulus histograms were constructed of the response of this Psol neuron tested
at different sinusoidal stimulus frequencies, all delivered with the head maintained in the optimal plane. Stimulus frequencies are indicated for each panel.
The response lead head position by ⬃40° at a stimulus frequencies of 0.02–
0.40 Hz. At the highest frequency examined, the response lagged head position
by 20 –30°. Numbers in each panel refer to the number of stimulus cycles that
were used to obtain the peristimulus histograms. XII, hypoglossal nucleus.
Static roll responses of Psol neurons
In addition to testing each suspected Psol neuron with vestibular sinusoids, we examined the static responses of Psol
then transferred onto one of four templates spaced about 500 ␮m apart
representing the rostrocaudal extent of the Psol.
RESULTS
Activity evoked in Psol neurons by vestibular stimulation:
optimal and null response planes
We recorded from a total of 97 neurons, 74 of which were
localized to the Psol. Sinusoidal oscillation of the rabbit about
its longitudinal axis modulated the activity of Psol neurons
(Fig. 2). When the rabbit was rotated onto the side that was
ipsilateral to the recorded Psol neuron, an increase in discharge
rate was evoked. When the rabbit was rolled onto the side
contralateral to the recorded Psol neuron, there was a decrease
in discharge rate. Rotation of the rabbit about its vertical axis
(yaw stimulation) failed to modulate Psol activity.
The average discharge rate during sinusoidal stimulation of
74 Psol neurons was 13.3 ⫾ 9.5 (SD) imp/s. The average
resting discharge rate for a smaller sample (n ⫽ 21) of Psol
neurons was 9.6 ⫾ 10.5 imp/s. The discrepancy between these
FIG. 5. Phase of responses in Psol neurons. A: in 47 Psol neurons, the phase
of the vestibularly evoked responses relative to the sinusoidal forcing function
were measured at a stimulus frequency of 0.3– 0.4 Hz while the rabbit’s head
was maintained in an optimal plane. B: in 13 Psol neurons, a complete series
of phase measurements were made. The responses are consistent with convergent inputs from both the vertical semicircular canals and utricular otoliths.
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Only one neuron responded optimally to horizontal vestibular stimulation. This neuron was localized to the border between the Psol and the MVN.
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neurons using static roll-tilt (see METHODS). More than 80% of
recorded Psol neurons had a positive static roll-tilt response. A
subset of these neurons was also tested with periodic vestibular
step stimulation. The optimal response plane for evoking activity from these neurons was based on previous testing with
vestibular sinusoids. An example of a neuron that tested positive for static roll is illustrated in Fig. 3. This neuron responded when the rabbit was stepped onto its left side (Fig.
3A). A peristimulus histogram illustrating two cycles of step
roll-tilt indicates that the response did not adapt during the
brief (10 s) step (Fig. 3C). This neuron was localized to Psol at
a level that was 1,000 ␮m rostral to the caudal pole of the Psol
(Fig. 3, D and E).
Another Psol neuron, with a positive static roll-tilt test, was
examined with a series of sinusoidal frequencies (Fig. 4). The
evoked discharge of this neuron lead head position by ⬃40° at
a stimulus frequencies of 0.02– 0.10 Hz (Fig. 4D). However, at
the highest two frequencies, the gain of the response was
reduced and the phase of the response lagged head position by
20 –30°. This neuron was localized to the most rostral part of
the Psol, 2,000 ␮m rostral to the caudal pole of the Psol (Fig.
4C).
The phase of 47 Psol neurons, each with a static roll response, was compared using vestibular sinusoids at 0.30 – 0.40
Hz (Fig. 5A). The mean phase lead of this population was
39.5 ⫾ 5.1°. Only four neurons had a phase lag at the frequencies tested.
A full range of vestibular sinusoids was used to examine the
phase of the evoked discharge in a subset of 13/47 Psol neurons
(Fig. 5B). The phase lead with respect to head position decreased by ⬃40° as the frequency of stimulation was increased
from 0.10 to 0.80 Hz.
Frequency dependence of null plane analysis
The foregoing data suggested that Psol neurons receive
convergent vestibular information. At least some of this convergence could be attributed to signals arising from the utricular otoliths and vertical semicircular canals. If this were true,
then it should be possible to obtain a frequency-dependent shift
in the null plane of a neuron. We measured the null plane at
two different frequencies (0.02 and 0.30 Hz) for the neuron
illustrated in Fig. 6. This neuron had a positive response to
static tilt, demonstrating that it received otolith information. In
such neurons, it was not feasible to conclude that the response
at higher frequencies was driven by either otoliths, semicircular canals or combinations of these inputs. The null plane for
the higher frequency corresponded to a null plane of 45°
counterclockwise (CCW; Fig. 6B). The null plane at the lower
frequency corresponded to a head orientation of 17° CCW
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FIG. 6. Influence of stimulus frequency
on measurement of null plane. The vestibular null plane was measured in a left Psol
neuron at 2 different stimulus frequencies.
Peristimulus histograms (B and C) were
obtained with the head maintained in the
positions shown in A and during sinusoidal
vestibular stimulation with a 0.30 and 0.02
Hz. The null plane was frequency dependent. The null plane at 0.30 Hz (B) aligned
with a head orientation of 45° CCW with
respect to the longitudinal axis. The null
plane in C aligned with a head orientation
of 17° CCW with respect to the longitudinal axis. The numbers in each panel refer to
the number of stimulus cycles that were
used to obtain the peristimulus histograms.
PARASOLITARY VESTIBULAR PHYSIOLOGY
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vestibular stimulation about the longitudinal axis. Twenty-six
neurons were localized within the Psol and had optimal response planes consistent with stimulation of the ipsilateral
anterior semicircular canal (E). These neurons were concentrated in the most rostral region of Psol (Fig. 8D). Twenty-nine
neurons had optimal response planes consistent with stimulation of the ipsilateral posterior semicircular canal (F). A topographic concentration of these neurons within the Psol was not
evident. Finally, four neurons were found with a Type 3
response (䡲). These neurons responded to sinusoidal rotation
onto the left and right sides.
Vestibularly evoked oscillations in Psol neurons
In most Psol neurons vestibularly evoked discharges were
stationary. They were repeatedly evoked, for tens of minutes,
during sinusoidal rotation of the rabbit about the longitudinal
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FIG. 7. Distribution of optimal response planes for Psol neurons. Null
planes were measured in 47 Psol neurons at sinusoidal stimulus frequencies of
0.20 – 0.40 Hz. The optimal response planes of these neurons clustered about
the anatomical orientation of the ipsilateral anterior and posterior semicircular
canals. The numbers adjacent to each bracketed set of optimal response planes
indicate the mean for that cluster and the number, n, of Psol neurons included
in the average.
(Fig. 6C). These data suggest convergence of at least two
different vestibular primary afferents at the level of the Psol
neuron.
Distribution of optimal response planes for Psol neurons
We measured the null planes in 47 Psol neurons at stimulus
frequencies of 0.20 – 0.40 Hz. The optimal response planes of
most of these neurons aligned with the anatomical orientation
of either the ipsilateral anterior or posterior semicircular canals
(Fig. 7).
Topographic distribution of optimal response planes mapped
onto the Psol
For each neuron from which we recorded, a microlesion was
made to mark its location. The location of these marking
lesions was reconstructed from transverse histological sections
through the Psol and plotted onto standard transverse schematics spaced 500 ␮m apart (Fig. 8). The locations of 97 recorded
neurons are represented. Of these neurons, 21 were unresponsive to vestibular stimulation about the longitudinal axis (*).
Most of these unresponsive neurons (20/21) were found outside of the Psol. Only one Psol neuron was unresponsive to
vestibular stimulation about the longitudinal axis. The null
planes of seventeen neurons were not measured (▫). Of these
neurons, 15/17 were within the Psol and were sensitive to
FIG. 8. Localization of vestibularly responsive neurons within Psol. The
left dorsal brain stem is illustrated in transverse sections, spaced ⬃500 ␮m
apart in A–D, left. The numbers to the right of each section indicate the
distance from the caudal pole of the Psol. The area that includes Psol in each
section is indicated. This area is shown at higher magnification in the right
column. The locations of Psol neurons, confirmed by recovery of microlesions,
are plotted in the higher magnification sections. *, location of neurons that
lacked a vestibularly driven response; E, neurons whose optimal response
planes corresponded to the orientation of the left anterior-right posterior
semicircular canals; ●, neurons with optimal response planes corresponding to
the orientation of the left posterior-right anterior semicircular canals; 䡲, neurons that responded to rotation onto both the left and right sides; ▫, neurons that
were vestibularly responsive, but in which null planes were not measured.
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axis. When the vestibular stimulus was stopped, the discharge
of these responses returned to nonperiodic spontaneous levels.
However, the vestibularly evoked discharge of ⬃5% of Psol
neurons was not stationary. In these neurons, sinusoidal vestibular stimulation about the longitudinal axis evoked increased
discharge when the rabbit was rotated onto the side that was
ipsilateral to the recorded Psol neuron (Fig. 9A). However,
when the sinusoidal vestibular stimulation was stopped, the
neuron continued to oscillate at a frequency that reflected its
stimulus history (Fig. 9, B and C). These slow oscillations
lasted 100 –300 s.
DISCUSSION
Psol and its transmitter-specific circuitry
In the rabbit the Psol consists of a cluster of 2,300 neurons
that lies dorsolateral to the tractus solitarius in its caudal most
aspect and wedged between the MVN and DVN at its most
rostral aspect (Fig. 10) (Barmack et al. 1998). In this study we
Comparison of the physiology of Psol neurons with the
physiology of other neurons receiving projections from Psol
neurons
The optimal response planes for neurons in the nucleus
reticularis gigantocellularis (NRGc) (Fagerson and Barmack
1995), ␤-nucleus (Barmack et al. 1993a), dmcc (Barmack
1996), and climbing fiber responses of Purkinje cells in the
uvula-nodulus (Barmack and Shojaku 1995; Fushiki and Barmack 1997), like those of Psol neurons, were consistent with
stimulation of the vertical semicircular canals and utricular
otoliths. In each of these structures, the optimal response
planes correspond to the anatomical planes of the vertical
semicircular canals or utricular otoliths. In none of the Psol,
NRGc, ␤-nucleus, dmcc, or uvula-nodulus was there any physiological evidence of activity modulated by vestibular stimulation in the plane of the horizontal semicircular canal.
There are differences as well as similarities in the evoked
neuronal activity in each of these locations. For example, we
found that Psol neurons lacked optokinetic sensitivity. However, in the ␤-nucleus and uvula-nodulus, many of the neurons
driven by vestibular stimulation are also responsive to vertical
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FIG. 9. Vestibularly induced oscillations in Psol neurons. The responses of
some Psol neurons persisted after the sinusoidal stimulus was stopped. The
discharge of this neuron, recorded from the right Psol, continued to oscillate
after sinusoidal roll stimulation. A: the peristimulus histograms for vestibular
stimulation about the longitudinal axis at 0.3 and 0.5 Hz are illustrated. B:
when the vestibular stimulation stopped, the Psol neuron continued to oscillate.
C: the oscillations attenuated over 1–2 min as indicated by the decreased
number of action potentials in each burst measured immediately after the
vestibular stimulation was stopped (0 min) and at 1 and 2 min later.
have shown that Psol neurons respond to vestibular stimulation. In particular we have shown that most Psol neurons are
modulated during static and dynamic roll-tilt about the longitudinal axis. Psol neurons have optimal response planes that
are consistent with stimulation of either the ipsilateral anterior
or posterior semicircular canals and the utricular otoliths. Psol
neurons are not modulated by rotation about the vertical axis
nor are they modulated by optokinetic stimulation.
The identity of the Psol as the exclusive source of the
vestibular GABAergic projection to both the ␤-nucleus and the
dmcc is reinforced by observations concerning the retrograde
and transneuronal transport of the ␣-herpes virus following
infection of the uvula-nodulus of gerbils (Kaufman et al. 1996).
Forty-eight hours after a postuvula-nodulus infection, the
␣-herpes virus was found only in the dmcc and ␤-nucleus.
However, after a 50-h survival period, the virus labeled a cell
group that corresponded to the location of Psol, contralateral to
uvula-nodulus injection site. Of equal interest, following the
50-h survival period, other neurons within the vestibular complex were only sparsely labeled.
The Psol is embedded in neuronal circuitry that provides an
important source of vestibular climbing fiber inputs to the
cerebellum. This transmitter-specific circuitry is illustrated in
Fig. 10. Stimulation of the vertical semicircular canals or the
utricular otolith activates glutamatergic primary vestibular afferents that synapse on ipsilateral Psol neurons (Raymond et al.
1984). Psol neurons are GABAergic and project to the ipsilateral NRGc and to the dmcc and ␤-nucleus (Barmack et al.
1998). The dmcc and ␤-nucleus, in turn, project to the contralateral cerebellar uvula-nodulus (Barmack 1996; Brodal
1976; Eisenman et al. 1983; Kaufman et al. 1996; Sato and
Barmack 1985; Whitworth et al. 1983). The transmitters for
this projection include aspartate or glutamate (Wiklund et al.
1982; Zhang and Ottersen 1993) and corticotropin-releasing
factor (Barmack and Young 1990; Mugnaini and Nelson 1989;
Young et al. 1986). The Purkinje cells of the uvula-nodulus
project onto the ipsilateral Psol (N. H. Barmack, Z.-Y. Qian,
and J. Yoshimura, unpublished results).
PARASOLITARY VESTIBULAR PHYSIOLOGY
3567
optokinetic stimulation (Barmack and Shojaku 1995; Barmack
et al. 1993b; Fushiki and Barmack 1997). Optokinetic information from the medial terminal nucleus converges directly
onto neurons in the ␤-nucleus (Giolli et al. 1984).
cessation of long-term periodic vestibular stimulation
(Kleinschmidt and Collewijn 1975). These vestibularly
evoked oscillations may reflect a fundamental system response to periodic motion.
Vestibularly evoked oscillations in Psol neurons
Comparison of Psol with “classical” vestibular nuclei
Some Psol neurons were driven into oscillations by repetitive sinusoidal roll stimulation. In this regard, these Psol
neurons are similar to, and maybe responsible for, climbing
fiber oscillations that we have previously recorded from
Purkinje neurons in the uvula-nodulus (Barmack and Shojaku 1992). There are two classes of explanations that could
account for these oscillations: the oscillations represent
intrinsic membrane properties of certain neurons and the
oscillations represent network properties of the vestibular
primary afferent 3 Psol 3 ␤-nucleus 3 uvula-nodulus 3
Psol circuit. In either case, these oscillations comprise an
adaptive function that could account for the persistence of
periodic reflexive eye movements that last 1–2 min after the
The Psol is the one vestibular nucleus for which we can
identify a clear encoding function. Psol neurons encode
vestibular spatial orientation about the longitudinal axis.
The characteristics of Psol neurons differ from the more
“classic” vestibular neurons in several respects: 1) the Psol
is composed exclusively of an homogenous group of small
GABAergic, principal neurons, without evidence of inhibitory interneurons (Barmack et al. 1998). Other vestibular
nuclei are composed of a mixture of non-GABAergic principal neurons and inhibitory neurons that may be GABAergic or glycinergic (Behar et al. 1994; Kumoi et al. 1987). 2)
The Psol lacks a commissural projection. Other vestibular
nuclei (with the exception of Deiter’s nucleus) have a com-
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FIG. 10. Transmitter-specific circuitry related to the
parasolitary nucleus and central vestibular function.
Several transmitter-specific circuits are represented in
this schematic. One projection, represented in green,
expresses glutamate: 1) vestibular primary afferents 3
vestibular complex and cerebellum. Two projections
express GABA (red): 1) Psol 3 ␤-nucleus, dorsomedial
cell column and nucleus reticularis gigantocellularis
(NRGc) and 2) cerebellar folia 9 –10 3 Psol. One
projection expresses acetylcholine (blue): medial vestibular nucleus 3 cerebellar folia 9 –10. This projection is
primarily ipsilateral but also includes a contralateral
component. One circuit expresses acetylcholine (blue)
and GABA (red): NPH 3 dorsal cap (dc). This projection is primarily contralateral but also includes an ipsilateral component (Barmack et al. 1993a; Caffé et al.
1996; De Zeeuw et al. 1993). One projection expresses
both glutamate (green) and corticotropin-releasing factor (CRF) (yellow): vestibular inferior olive (␤-nucleus
and dorsomedial cell column) 3 contralateral cerebellum folia 9 –10. Abbreviations: Amb, nucleus ambiguus;
␤, ␤-nucleus; CF, climbing fiber; CRF, corticotropinreleasing factor; dc, dorsal cap of Kooy; DAO, dorsal
accessory olive; dmcc, dorsomedial cell column; icp,
inferior cerebellar peduncle; Fl, flocculus; Gr, granule
cell; LRN, lateral reticular nucleus; MAO, medial accessory olive; MF, mossy fiber; P, Purkinje neuron; PF,
parallel fiber; PFl, paraflocculus; PO, principal olive;
Pyr, pyramidal tract; 12n, hypoglossal nerve.
3568
N. H. BARMACK AND V. YAKHNITSA
Functional implications of Psol circuitry
It is interesting to speculate about the possible function of
the circuitry in which the Psol is embedded. Primary vestibular
inputs, say on the left side, would activate left Psol neurons.
These neurons would in turn inhibit neurons in the left ␤-nucleus and dmcc. This would decrease the climbing fiber signals
to the right uvula-nodulus. Because the modulation of the
simple spikes of cerebellar Purkinje cells is antiphasic to
climbing fiber signals, a decrease in climbing fiber input would
cause an increase in simple spike discharge (Fushiki and Barmack 1997). This increased simple spike discharge in the right
uvula-nodulus would reduce the activity of neurons in the right
Psol. Thus activation of neurons in one Psol by primary vestibular afferents would lead to a reciprocal reduction in activity
in the contralateral Psol mediated by: left Psol 3 left ␤-nucleus and dmcc 3 right nodulus 3 right Psol.
There is little doubt that this circuitry is critical for providing
information about spatial orientation about the longitudinal
axis. It remains for future experiments to determine the behavioral significance of this circuitry. Experiments that link its role
to otolithic function, vestibular adaptation and possible vestibular-autonomic interactions seem most promising.
We thank M. Westcott-Hodson for expert histological, technical, and artistic
assistance. We thank S.-H. Park for technical and graphic assistance. The
antiserum to GAD was provided by the Laboratory of Clinical Science,
National Institute of Mental Health. The antiserum was developed by Dr. I. J.
Kopin in association with Drs. W. Oertel, D. E. Schmechel and M. Tappaz.
This research was supported by National Eye Institute Grant EY-04778.
Address for reprint requests: N. H. Barmack, Neuronal Plasticity Group,
L111, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd.,
Portland, OR 97201.
Received 4 January 2000; accepted in final form 6 March 2000.
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