Stimulation Of Labyrinth Research Articles

Timing of low frequency responses of anterior and posterior canal vestibulo-ocular neurons in alert cats.

The pitch vertical vestibulo-ocular reflex (VOR) is accurate and symmetrical when tested in the normal upright posture, where otolith organ and central velocity storage signals supplement the basic VOR mediated by the semicircular canals. However, when the animal and rotation axis are together repositioned by rolling 90 degrees to one side, head forward pitch rotations that excite the anterior semicircular canals elicit a more accurately timed VOR than do oppositely directed rotations that excite the posterior canals. This suggests that velocity storage of posterior canal signals is lost when the head is placed on its side. We recorded from 47 VOR relay neurons, second-order vestibulo-ocular neurons, of alert cats to test whether asymmetries are evident in the responses of neurons in the medial and superior vestibular nuclei during earth-horizontal axis rotations in the normal upright posture. Neurons were identified by antidromic responses to oculomotor nucleus stimulation and orthodromic responses to labyrinth stimulation, and were classified as having primarily anterior, posterior, or horizontal canal input based on response directionality. Neuronal response gains and phases were recorded during 0.5 Hz and 0.05 Hz sinusoidal oscillations in darkness. During 0.5 Hz rotations, anterior canal second-order vestibulo-ocular neurons responded approximately in phase with head velocity (mean phase re head position, +/- SE, 80 degrees +/- 3 degrees, n=18), as did posterior canal second-order vestibulo-ocular neurons (mean phase 81 degrees +/- 1 degree, n=25). Lowering the rotation frequency to 0.05 Hz resulted in only slight advances in response phases of individual anterior canal second-order vestibulo-ocular neurons (mean phase 86 degrees +/- 6 degrees, mean advance 7 degrees +/- 5 degrees, n=12). In contrast, posterior canal second-order vestibulo-ocular neurons behaved more like semicircular canal afferents, with responses markedly phase-advanced (mean advance 28 degrees +/- 5 degrees, n=14) by lowering rotation frequency to 0.05 Hz (mean phase 111 degrees +/- 5 degrees, n=14). In summary, low frequency responses of anterior and posterior canal second-order vestibulo-ocular neurons recorded during horizontal axis pitch correspond to the VOR they excite during vertical axis pitch. These results show that velocity storage is evident at anterior but not posterior canal second-order vestibulo-ocular neurons. We conclude that responses of posterior canal second-order vestibulo-ocular neurons are insufficient to explain the accurate low frequency VOR phase observed during backward head pitch in the upright posture, and that velocity storage or otolith signals required for VOR accuracy are carried by other neurons.

Directional sensitivity of anterior, posterior, and horizontal canal vestibulo-ocular neurons in the cat.

Neurons subserving the vestibulo-ocular reflex transform the directionality and timing of input from semicircular canals into commands that are appropriate to rotate the eyes in a compensatory fashion. In order to assess the degree to which this transformation is evident in vestibular nucleus neurons of alert cats, we recorded the extracellular discharge properties of 138 second-order vestibular neurons in the superior and medial vestibular nucleus, including 64 neurons identified as second-order vestibulo-ocular neurons by antidromic responses to oculomotor nucleus stimulation and short-latency orthodromic responses to labyrinth stimulation (1.3 ms or less). Neuronal response gains and phases were recorded during 0.5-Hz sinusoidal oscillations about many different horizontal axes and during vertical axis rotations to define neuronal response directionality more precisely than in past studies. Neurons with spatial responses similar to anterior semicircular canal afferents were found to have more diverse maximal activation direction vectors than neurons with responses resembling those of posterior or horizontal canal afferents. The mean angle from neuron response vector to the axis of the nearest canal or canal pair was 19 degrees for anterior canal second-order neurons (n=28) and 20 degrees for anterior canal second-order vestibulo-ocular neurons (n=18), compared with 11 degrees for posterior canal second-order neurons (n=43) and 11 degrees for posterior canal second-order vestibulo-ocular neurons (n=25). Only two second-order vestibulo-ocular neurons (3%) showed a marked dependence of response phase on rotation direction, which is indicative of convergent inputs that differ in both dynamics and directionality. This suggests that spatiotemporal convergence is uncommon in the three-neuron vestibulo-ocular reflex arc of the cat. Neuron vectors included many that were closely aligned with canal axes and several that were better aligned with oblique or superior rectus extraocular muscle excitation axis vectors. Only single examples of second-order vestibulo-ocular neuron vectors were approximately aligned with the pitch and roll coordinate axes. We conclude that second-order vestibulo-ocular neurons do not exclusively represent either the semicircular canal sensory coordinate frame or the extraocular muscle excitation motor coordinate frame, and instead are mostly distributed on a continuum between the input and output coordinate frames, with anterior canal neurons having the widest distribution of directionality.

Tuning in caudal fastigial nucleus units during natural and galvanic labyrinth stimulation.

Neurons of the caudal fastigial nucleus were investigated by means of single unit recordings. Natural vestibular stimuli were applied as well as galvanic labyrinth polarization. One-third of the neurons showed a convergence of vertical and horizontal canals. More than 80% of the neurons responded to polarization of both the ipsilateral and contralateral canals (binaural responders). Most neurons had a limited response range. Two classes of neurons could be distinguished: up to 1 Hz responders and up to 10 Hz responders. In addition a group of fastigial cells showed a tuning within a small range of frequencies (sharp-tuning responders).

Anatomical and theoretical observations on otolith repositioning for benign paroxysmal positional vertigo.

To determine if there is an anatomic basis for the assumption that loose, "rogue" otoliths presumed to arise from the utricular macula and theorized to cause benign paroxysmal positional vertigo (BPPV) by impinging on semicircular canal ampullae could be returned to their original site by a series of changes in the position of the head called particle repositioning maneuvers (PRMs). Further, if such otolith movement were possible, once they were replaced into the utricle, would they adhere to the utricular macula? Kodachrome photographs of 2-mm-thick macrosections of human temporal bones were available for evaluation. The bones were sectioned in horizontal, coronal, and sagittal planes. Rice grains were placed on the photographs of the cross-sections to demonstrate the possible paths taken by loose otoliths under the influence of gravity in different positions of the head. A study of cross-sections of the temporal bone shows that loose macular otoliths after PRMs would tend to fall into the lumen of the utricle. Once the patient assumes the erect position, however, repositioned otoliths would tend to fall into the near or utriculopetal side of the cupula of the posterior semicircular canal, which opens directly into the inferior portion of the utricle, and could cause labyrinth stimulation and BPPV by the same mechanism of misplaced otoliths on the opposite or far side of the cupula. Loose otoliths in the utricle could also stimulate the horizontal ampullae. PRMs do not remove or fix otoliths in any specific site in the labyrinth. Repositioning of loose otoliths onto the original site in the macula of the utricle, which lies superiorly in the vestibule, could not be accomplished by any of the repositioning maneuvers. If otoliths were to be repositioned on the utricular macula, there is no evidence that the otoliths would adhere to the macula when the patient assumes the erect position. The good results obtained by physiotherapeutic procedures suggest that some other mechanism than repositioning of otoliths is responsible for the relief of BPPV.

Vasopressin in the locus coeruleus and dorsal pontine tegmentum affects posture and vestibulospinal reflexes

Vasopressin (VP) acts on both the locus coeruleus (LC) neurons and the neighbouring dorsal pontine reticular formation (PRF) neurons by exciting them. Experiments performed in precollicular decerebrate cats have shown that microinjection of 0.25 x 10(-11) micrograms VP into the LC complex of one side increased the extensor rigidity of the ipsilateral limbs, while rigidity of the contralateral limbs remained unmodified or slightly decreased. The amplitude of modulation and thus the response gain of both the ipsilateral and the contralateral forelimb extensor triceps brachii to sinusoidal roll tilt of the animal (at 0.15 Hz, +/- 10 degrees), leading to stimulation of labyrinth receptors, decreased significantly, while there was only a slight decrease in phase lead of the responses. These effects occurred 5-10 min after the injection, were fully developed within 30 min and disappeared in about 2 h. VP activation of presumed noradrenergic LC neurons had a facilitatory influence on ipsilateral limb extensor motoneurons, either directly through the coeruleospinal (CS) pathway, or indirectly by inhibiting the dorsal PRF and the related medullary inhibitory reticulospinal (RS) neurons. Moreover, because the facilitatory CS neurons fire out-of-phase with respect to the excitatory VS neurons, we postulated that the higher the firing rate of the CS neurons in the animal at rest, the greater the disfacilitation affecting the limb extensor motoneurons during side-down animal tilt. These motoneurons would then respond less efficiently to the excitatory VS volleys elicited for the same direction of animal orientation, leading to a reduced gain of the EMG responses of the forelimb extensors to labyrinth stimulation. In contrast to these findings, unilateral injections of the same dose of VP immediately ventral to the LC, i.e., in the peri-LC alpha and the surrounding dorsal PRF, where presumed cholinergic neurons are located, decreased extensor rigidity in the ipsilateral limbs while that of the contralateral limbs either decreased or increased. The same injection also produced either a moderate or a marked increase in gain of the multiunit EMG response of the ipsilateral triceps brachii to animal tilt. In the first instance the response gain of the contralateral triceps brachii to animal tilt increased slightly, while the corresponding response pattern remained unmodified, as shown for the ipsilateral responses (increased EMG activity during ipsilateral tilt and decreased activity during contralateral tilt). In the second instance, however, the response gain of the contralateral triceps brachii showed only slight changes, while the pattern of response was reversed. These effects occurred 5-20 min after the injection, developed fully within 20-60 min and disappeared in 2-3 h. We postulated that VP increased the discharge of the dorsal PRF neurons and the related medullary inhibitory RS neurons of the injected side, leading to reduced postural activity of the ipsilateral limbs. However, because these inhibitory RS neurons fire out-of-phase with respect to the excitatory VS neurons, it appeared that the higher the firing rate of the RS neurons in the animal at rest, the greater the disinhibition affecting the limb extensor motoneurons during ipsilateral tilt. These motoneurons would then respond more efficiently to the same excitatory VS volleys elicited by given parameters of stimulation, leading to an increased gain of the EMG responses. The contralateral effects could be attributed to crossed excitation by dorsal PRF neurons of one side, either of medullary inhibitory RS neurons or of excitatory CS neurons of the opposite side, respectively. We conclude that VP controls posture and gain of the VS reflex by acting on LC neurons as well as on dorsal PRF and the related medullary inhibitory RS neurons.

Unilateral testing of utricular function.

A modified rotatory chair test is reported in which radial acceleration, generated by eccentric displacement of the subject during constant angular velocity, is exploited as a unilateral stimulation to the otolith organs. During constant angular rate rotation, the test subject is displaced laterally on the rotating turntable by 3.5 cm, so that one labyrinth becomes aligned with the rotatory axis while the second - eccentric - labyrinth is solely exposed to the altered gravito-inertial acceleration (GIA). Previously reported results showed that the direction of the response is independent of the direction of turntable rotation, ruling out any canal influence, and indicated that in a normal population the response, measured in one eye, was symmetrical for displacement of the left and right labyrinths. This mode of stimulus thus appears to elicit a unilateral otolith-ocular response (OOR). Examination of this unilateral OOR was extended in the present study; comparative testing with head-tilt to gravity, i.e. involving bilateral stimulation to the otolith organs, was carried out. Movements of both eyes were recorded (by three-dimensional video-oculography), in order to examine response conjugacy. To verify the specificity of the unilateral stimulus, tests were performed with patients who had previously undergone unilateral section of the vestibular nerve as treatment for acoustic neuroma. The eccentric displacement profile (EDP) and head-tilt stimulus each included ten cycles of left-right oscillation in order to permit signal averaging. In the normal subjects (n=12) the torsional component of the OOR proved to be both labyrinth-symmetrical and conjugate, during both bilateral and unilateral otolith stimulation. OOR gain (ocular torsion/GIA tilt) was higher for bilateral than unilateral stimulation. Bilateral OORs, obtained from three of the five unilaterally deafferented patients, proved less symmetrical and conjugate than in the normals. Unilateral OORs in all five patients were characteristically asymmetrical, with little or no response during stimulation of the diseased labyrinth.

Interdependence of spatial properties and projection patterns of medial vestibulospinal tract neurons in the cat.

Activity of vestibular nucleus neurons with axons in the ipsi- or contralateral medial vestibulospinal tract was studied in decerebrate cats during sinusoidal, whole-body rotations in many planes in three-dimensional space. Antidromic activation of axon collaterals distinguished between neurons projecting only to neck segments from those with collaterals to C6 and/or oculomotor nucleus. Secondary neurons were identified by monosynaptic activation after labyrinth stimulation. A three-dimensional maximum activation direction vector (MAD) summarized the spatial properties of 151 of 169 neurons. The majority of secondary neurons (71%) terminated above the C6 segment. Of these, 43% had ascending collaterals to the oculomotor nucleus (VOC neurons), and 57% did not (VC neurons). The majority of VOC and VC neurons projected contralaterally and ipsilaterally, respectively. Most C6-projecting neurons could not be activated from oculomotor nucleus (V-C6 neurons) and projected primarily ipsilaterally. All VO-C6 neurons projected contralaterally. The distributions of MADs for secondary neurons with different projection patterns were different. Most VOC (84%) and contralaterally projecting VC (91%) neurons had MADs close to the activation vector of a semicircular canal pair, compared with 54% of ipsilaterally projecting VC (i-VC) and 39% of V-C6 neurons. Many i-VC (44%) and V-C6 (48%) neurons had responses suggesting convergent input from horizontal and vertical canal pairs. Horizontal and vertical gains were comparable for some, making it difficult to assign a primary canal input. MADs consistent with vertical-vertical canal pair convergence were less common. Type II yaw or type II roll responses were seen for 22% of the i-VC neurons, 68% of the V-C6 neurons, and no VOC cells. VO-C6 neurons had spatial properties between those of VOC and V-C6 neurons. These results suggest that secondary VOC neurons convey semicircular canal pair signals to both ocular and neck motor centers, perhaps linking eye and head movements. Secondary VC and V-C6 neurons carry more processed signals, possibly to drive neck and forelimb reflexes more selectively. Two groups of secondary i-VC neurons exhibited vertical-horizontal canal convergence similar to that present on neck muscles. The vertical-vertical canal convergence present on many neck muscles, however, was not present on medial vestibulospinal neurons. Spatial transformations achieved by the vestibulocollic reflex may occur in part on secondary neurons but further combination of canal signals must take place to generate compensatory muscle activity.

Neurotransmitters of Vestibular Commissural Inhibition in the Cat

The present study examined transmitters that regulate commissural inhibition. Extracellular spikes of a single vestibular neuron were recorded in decerebrated cats. Multibarreled electrodes were filled with transmitter candidates (GABA and glycine), their specific antagonists (bicuculline, strychnine) and 2 M NaCl for extracellular recording. After isolation of a type I neuron, chemicals were iontophoretically applied to examine their effects on the activity of the neuron. The results were as follows. Commissural inhibition caused by electrical stimulation of the contralateral labyrinth was not abolished by the application of strychnine (a glycine antagonist), but was abolished by bicuculline (a GABA antagonist). Commissural inhibition was not abolished by phaclofen. Some bicuculline-sensitive neurons, with a short-latency commissural inhibition (presumably disynaptic inhibition), showed spacial summation when the conditioning stimulation (contralateral vestibular nerve stimulation) was applied with the test stimulation (vestibular nucleus stimulation). It was concluded that commissural inhibition was activated by the GABAA receptor, but not by the GABAB receptor, that the inhibitory type I neurons located in the contralateral vestibular nucleus were GABAergic, and that inhibitory type II neurons were also GABAergic neurons.

Neuronal responses to vestibular stimulation in the guinea pig hypothalamic paraventricular nucleus.

We investigated the effects of caloric stimulation on neuronal activity in the hypothalamic paraventricular nucleus (PVN) in anesthetized guinea pigs. Hot water stimulation of the contralateral labyrinth produced excitation in 29.4% of the PVN neurons tested, while cold water produced excitation in 22.2% of the neurons. Hot water resulted in inhibition of 22.4% of the neurons and cold water inhibition of 24.7% of the neurons. Intracranial vestibular nerve section greatly reduced responsiveness of the PVN neurons to caloric stimulation, indicating that the majority of the responses observed were vestibular in origin. The response pattern of the individual PVN neurons was similar following hot and cold water stimulation and after stimulation of the contralateral and ipsilateral labyrinths. These results suggest that the PVN neurons receive vestibular afferents bilaterally according to the intensity of vestibular stimulation, with the information received probably integrated in the hypothalamus to participate in vestibulo-autonomic reflexes.

Monitoring of Anterior Cervical Spinal Cord Function

Anterior surgery is frequently chosen for treatment of cervical myelopathy. However, intraoperative spinal cord recording has rarely been used to monitor the function of the ventral columns. We report a method of monitoring evoked spinal cord potentials useful for detection of minor injury of the anterior spinal cord. Evoked spinal cord potentials elicited in cats by thoracic spinal cord and labyrinth stimulation were studied. Evoked intraspinal field potentials recorded after labyrinth stimulation were confirmed to originate from the vestibulospinal tract in the ventral columns. Low-amplitude potentials were recorded from the posterior epidural space. However, this method has not been used clinically because of difficulty in obtaining selective stimulation in humans. Spinal cord potentials evoked by thoracic stimulation were recorded from the anterior and posterior epidural spaces. The amplitude of the potentials was large enough to permit quantitation of neural function. We confirmed that anterior recording was more sensitive in detecting ventral column injury than posterior recording was. Based on these findings, we used anterior recording from the disc clinically for anterior spinal cord monitoring during anterior cervical surgery.

Inputs from the ipsilateral and contralateral vestibular apparatus to behaviorally characterized abducens neurons in rhesus monkeys.

1. We made extracellular recordings from neurons in the abducens nuclei of alert rhesus monkeys during electrical stimulation of the vestibular labyrinths with brief current pulses and during smooth pursuit, steady fixation, and the vestibuloocular reflex (VOR) evoked by passive head turns. The responses to electrical stimuli were compared with quantitative measures of the sensitivity of each neuron to eye position and eye velocity. We also compared the strengths of the vestibular inputs from the labyrinths ipsilateral and contralateral to the side of recording. 2. Abducens neurons showed transient excitation after a current pulse was applied to the contralateral labyrinth and transient inhibition after stimulation of the ipsilateral labyrinth. The latency of excitation had a mean value of 1.7 ms and a median value of 1.5 ms. Latency was unimodally distributed with little variation among neurons. Neurons with large responses showed a second phase of excitation that started 2.5 ms after the stimulus. 3. In two of three monkeys, the excitatory responses of abducens neurons to electrical stimulation of the contralateral labyrinth were approximately 3 times as large as their inhibitory responses to stimulation of the ipsilateral labyrinth. The difference in response size was not observed in the third monkey. The asymmetry in the size of the electrically evoked inputs from the two labyrinths was associated with a smaller asymmetry in responses of abducens neurons during the VOR evoked by passive head turns. The increase in firing rate during head rotation away from the side of the recording was almost always larger than the decrease in firing rate during head rotation toward the side of the recording. 4. The size of the neuronal response to electrical stimulation was correlated with the magnitude of the change in discharge rate during eye movements. Single or multiple regression of measures of response amplitude against eye position threshold, sensitivity to eye position, sensitivity to eye velocity, and baseline discharge rate yielded correlation coefficients that ranged from 0.26 to 0.92 in different monkeys. The existence of positive correlations is consistent with a role of the intrinsic properties of abducens neurons in determining recruitment order. However, the existence of large amounts of variability within most of the samples suggests that the recruitment order of abducens neurons also depends on the discharge properties of the afferents to each abducens neuron.

Posterior canal-activated excitatory vestibuloocular relay neurons participate in the vestibulocortical pathways in cats.

We have previously reported that axon collaterals of posterior canal-activated excitatory vestibular (PC) neurons project to the contralateral oculomotor nucleus, and rostrally to the thalamus. To elucidate the vestibulothalamocortical pathways we investigated the synaptic connections of the PC neurons with the thalamic neurons by post-spike averaging of compound potentials triggered by spikes of the PC neuron in anesthetized cats. The averaged field potential evoked in the ventrobasal complex (VBC) revealed a spike followed by a negative wave. Latencies of the wave ranged from 0.8 to 1.5 ms. Next, we examined the location and axonal projection of 36 thalamic neurons which were activated by nose-up head rotation and by contralateral labyrinth stimulation. Most of them were located in the VBC and some in the medial geniculate body. Thirteen of the 36 neurons were antidromically activated from the anterior suprasylvian sulcus or postcruciate dimple of the cortex. These results suggest that the PC neurons participate, at least in part, in the vestibulocortical pathways contributing to spatial orientation.

Microinjections of GABAergic agents in the locus coeruleus modify the gain of vestibulospinal reflexes in decerebrate cats.

1. Precollicular decerebrate cats show a good postural activity in the four limbs and a small-amplitude vestibulospinal (VS) reflex, as revealed by recording the EMG response of the triceps brachii to sinusoidal roll tilt of the animal at 0.15 Hz, +/- 10 degrees. This preparation was used to study whether inactivation of the locus coeruleus (LC) elicited by local administration either of the GABA-A agonist muscimol or of the GABA-B baclofen produced changes in posture as well as in gain of the VS reflexes. 2. Microinjection into the LC of one side of 0.13-0.25 microliter of a muscimol or baclofen solution (at 2.5 or 1 microgram/microliter saline, respectively) stained with 5% pontamine, usually decreased the extensor tonus in the ipsilateral limbs and to a lesser extent also in the contralateral limbs. However, the amplitude of modulation and thus the gain of the first harmonic component of the multiunit EMG responses of the ipsilateral and to a lesser extent also of the contralateral triceps brachii to the same parameters of labyrinth stimulation increased. The phase angle of the responses remained nearly unchanged by this treatment. The effects appeared 5-10 min after the injection of muscimol, fully developed in 30 min and progressively declined within the following 2-2.5 hours. 3. The increased gain of the VS reflexes acting on the triceps brachii did not depend on the decreased postural activity following the injection of the GABA-A or GABA-B agonist, since it was still observed if the reduced EMG activity following the injection was compensated by an increased static stretch of the muscle. Moreover, the postural and reflex changes described above were not due to irritative events following the injection, since they were not observed in control experiments following injection of 0.25 microliter saline within the LC-complex. On the other hand, postural and reflex changes opposite in sign to those elicited by muscimol or baclofen were obtained by local injection into the LC-complex of a GABA-A or GABA-B antagonist (0.25 microliter of bicuculline or faclofen at 8 micrograms/microliters saline). 4. In some experiments, the decrease in postural activity of the forelimbs after injection of muscimol into the LC complex was followed by transient episodes of postural atonia, which affected not only the ipsilateral but also the contralateral triceps muscles.(ABSTRACT TRUNCATED AT 400 WORDS)

Posterior canal-activated vestibulocortical pathways in cats

This study was undertaken to investigate vestibulothalamocortical pathways in anesthetized cats. Synaptic connections of posterior canal-activated excitatory vestibuloocular relay (PC) neurons to thalamic neurons were examined by a spike-triggered averaging technique. The averaged potentials evoked in the ventrobasal complex of the thalamus revealed a negative wave with latencies from 0.8 to 1.5 ms. Thirty-six thalamic neurons, which were activated by nose-up head rotation and by contralateral labyrinth stimulation, were mainly located in the ventrobasal complex. Thirteen of these neurons were antidromically activated from the anterior suprasylvian sulcus or postcruciate dimple of the cortex. These results suggest that the PC neurons participate, at least in part, in the vestibulocortical pathways contributing to spatial orientation.

The use of focused ultrasound for stimulation of receptor’s nervous structures

It has been shown that short and relatively intense pulses of focused ultrasound (FUS) are able to stimulate selectively a variety of nervous structures [L. R. Gavrilov, Ultrasonics 22, 132–138 (1984)]. Different tactile, temperature (warmth and cold), and various pain sensations can be produced in the skin at the surface of the body. Pain sensations can also be produced in deep-seated structures, e.g., joints and muscles. Pulsed FUS acting on electroreceptors of skates induced spikes of neuronal activity. Stimulation of the ear labyrinth in humans with normal hearing by amplitude-modulated FUS induced hearing sensations that corresponded to the envelope of the amplitude-modulated ultrasonic signal. In similar circumstances deaf people, with clinically diagnosed destruction of the hair cells in the labyrinth, perceived the FUS signals. The mechanism of all these physiological phenomena has been attributed primarily to a mechanical effect of the FUS stimulation of the nerve structures. FUS stimulation has been applied successfully to the clinical diagnosis of a number of neurological and dermatological diseases and hearing disorders involving changes in the perception of various sensations.

Modulation of vestibulospinal reflexes through microinjection of an alpha 1-adrenergic antagonist in the dorsal pontine tegmentum of decerebrate cats.

1. The possibility that the norepinephrine (NE)-containing locus coeruleus (LC) neurons produce changes in posture as well as in gain of the vestibulospinal (VS) reflexes by acting on the dorsolateral pontine tegmentum (DPT) and the related medullary inhibitory reticulospinal (RS) system through alpha 1-adrenoceptors has been investigated in decerebrate cats. 2. Injection of the alpha 1-adrenergic antagonist prazosin PRZ (0.25 microliter at 0.1-1 microgram/microliter solvent) into the DPT, namely in the dorsal pontine reticular formation (pRF), as well as in the peribrachial nucleus of one side, decreased the postural activity in the ipsilateral limbs while increasing that of the contralateral limbs. In addition, the amplitude of modulation and thus the gain of the multiunit EMG responses of the ipsilateral and to a lesser extent of the contralateral triceps brachii to roll tilt of the animal at 0.15 Hz, +/- 10 degrees, increased. These effects appeared 5-10 min after the injection, reached the highest values in about 40-60 min and persisted for additional 1.5-2 h before disappearing. 3. The effects were site-specific and to some extent dose-dependent. However, neither changes in posture nor in gain of the VS reflexes were obtained after injection in the effective area of an equal volume of solvent. 4. In order to account for these findings it was postulated that the alpha 1-antagonist blocks the tonic inhibitory influence that the NE-containing LC neurons exert on ipsilateral DPT either by exciting through alpha 1-receptors interposed inhibitory interneurons, or by inhibiting presynaptically excitatory afferents to the same pontine tegmental structures. The increased discharge of these neurons and the related medullary inhibitory RS neurons would reduce the postural activity in the ipsilateral limbs. However, since the inhibitory RS neurons show a response pattern to tilt opposite in sign to that elicited by the excitatory VS neurons, we could expect that for a given labyrinth signal, the increased discharge of the RS neurons in the animal at rest would lead to a greater disinhibition of limb extensor motoneurons during ipsilateral tilt. These motoneurons would then respond more efficiently to the same excitatory volleys elicited by given parameters of stimulation, thus leading to an increased gain of the EMG responses of forelimb extensors to labyrinth stimulation. The possibility that the DPT of one side activates inhibitory RS neurons of both sides explains why PRZ increases the gain of the VS reflexes not only ipsilaterally but also contralaterally to the side of the injection.(ABSTRACT TRUNCATED AT 400 WORDS)

Vestibular inputs to brain stem neurons that participate in motor learning in the primate vestibuloocular reflex.

1. Previous studies have described a subpopulation of interneurons in the vestibuloocular reflex (VOR) pathways that express large changes in their responses to head turns in conjunction with motor learning in the VOR. These neurons are called flocculus target neurons (FTNs) because they are inhibited at monosynaptic latencies by stimulation of the flocculus and ventral paraflocculus. 2. Electrical stimulation of the vestibular labyrinth revealed that FTNs receive excitatory monosynaptic inputs from the ipsilateral vestibular labyrinth and longer-latency, excitatory inputs from the contralateral labyrinth. 3. Our data show that commissural inhibition, which has been thought to be an important feature of vestibular processing, does not provide the dominant inputs from the contralateral labyrinth to FTNs. Instead, the inputs from both labyrinths are excitatory and may be functionally antagonistic. Changes in the balance of excitatory inputs from the two horizontal canals to FTNs could contribute to motor learning in the VOR.

Neurotransmitters in the vestibular commissural system of the cat.

The present study focused on the transmitters that control the vestibular neural activity and, in particular, that regulate commissural inhibition. Extracellular spikes of a single vestibular neuron were recorded in decerebrate cats. The seven barrels of the electrode, with the exception of the center barrel, were filled with transmitter candidates and their specific antagonists, while the center barrel was filled with 2 M NaCl for extracellular recording. After isolation of a type 1 neuron, chemicals were iontophoretically applied to examine their effects on its activity. The results were as follows: (1) GABA and glycine markedly decreased spontaneous firing of the neurons, while serotonin did not affect their activity. (2) Bicuculline abolished the inhibitory effects of GABA on the neurons. (3) Strychine abolished the effects of glycine. (4) Commissural inhibition induced by electrical stimulation of the contralateral labyrinth was not abolished by strychine but was abolished by bicuculline. We conclude that (1) vestibular type 1 neurons are controlled by GABAergic and glycinergic but not serotoninergic neurons, and (2) commissural inhibition is activated by the GABAA receptor, but not by the GABAB receptor.

Noradrenergic and cholinergic modulations of corticocerebellar activity modify the gain of vestibulospinal reflexes.

In addition to mossy fibers and climbing fibers, the cerebellar cortex receives noradrenergic and cholinergic afferents. Since the Purkinje (P) cells of the cerebellar vermis (culmen) respond to roll tilt of the animal with a discharge pattern that is out of phase with respect to that of the related lateral vestibular neurons, thus exerting a facilitatory influence on the gain of the vestibulospinal (VS) reflex, we tested the effects of local microinjection into the anterior vermis of noradrenergic and cholinergic agents on these reflexes. In decerebrate cats, unilateral microinjection in the paramedial zone B of the culmen of 0.25 microliters of small doses of alpha 1-, alpha 2-, and beta-noradrenergic agonists (i.e., metoxamine, clonidine, and isoproterenol, respectively) increased the response gain (in impulses/second per deg) of the EMG response of the ipsilateral and to some extent also of the contralateral triceps brachii to animal tilt (at 0.15 Hz, +/- 10 degrees). On the other hand local injection of the corresponding antagonists (i.e., prazosin, yohimbine, and propranolol) either decreased the gain of the ipsilateral triceps brachii to labyrinth stimulation or else prevented the occurrence of the effects induced by the corresponding agonists. An increase in gain of the VS reflexes was also elicited in other experiments by unilateral microinjection either of the nonselective cholinergic agonist carbachol or of the anticholinesterase eserine sulfate. Thus, the effects could be produced by increasing the naturally present amount of acetylcholine. Further experiments indicated that a bilateral increase in the response gain of the triceps brachii to labyrinth stimulation occurred after microinjection of a selective muscarinic (bethanechol) or nicotinic agonist (nicotine), while just the opposite result was obtained after microinjection of the corresponding muscarinic (scopolamine) and nicotinic (hexamethonium, D-tubocurarine) blockers. The effects of the noradrenergic and cholinergic agonists, which persisted for about two hours after the injection, were site specific and dose dependent. It appears, therefore, that the noradrenergic and cholinergic afferents to the cerebellar vermis intervene in the gain regulation of the VS reflexes, possibly by increasing the amplitude of modulation of the P cells to labyrinth stimulation.

Response of pontomedullary reticulospinal neurons to vestibular stimuli in vertical planes. Role in vertical vestibulospinal reflexes of the decerebrate cat.

1. To investigate the neural substrate of vestibulospinal reflexes in decerebrate cats, we studied the responses of pontomedullary reticulospinal neurons to natural stimulation of the labyrinth in vertical planes. Our principal aim was to determine whether reticulospinal neurons that terminate in, or are likely to give off collaterals to, the upper cervical segments had properties similar to those of the vestibulocollic reflex (VCR). 2. Antidromic stimulation was used to determine whether the neurons projected to the neck, lower cervical, thoracic, or lumbar levels. Dynamics of the responses of spontaneously firing neurons were studied with sinusoidal stimuli delivered at 0.05-1 Hz and aligned to the plane of body rotation, that produced maximal modulation of the neuron (response vector orientation). Each neuron was assigned a vestibular input classification of otolith, vertical canal, otolith + canal, or spatial-temporal convergence (STC). 3. We found, in agreement with previous studies, that the largest fraction of pontomedullary reticulospinal neurons projected to the lumbar cord, and that only a small number ended in the neck segments. Neurons projecting to all levels of the spinal cord had similar responses to labyrinth stimulation. 4. Reticulospinal neurons that received only vertical canal inputs were rare (1 of 67 units). Most reticulospinal neurons (48%) received predominant otolith inputs, 18% received otolith + canal input, and only 9% had STC behavior. These data are in sharp contrast to the results of our previous studies of vestibulospinal neurons. A considerable portion of vestibulospinal neurons receives vertical canal input (38%), fewer receive predominantly otolith input (22%), whereas the proportion that have otolith + canal input or STC behavior is similar to our present reticulospinal data. 5. The response vector orientations of our reticulospinal neurons, particularly those with canal inputs (canal, otolith + canal, STC) were predominantly in the roll quadrants. There was no evidence of convergence of inputs from like canals across the midline (e.g., right anterior + left anterior). 6. Two characteristics of the VCR, STC behavior and bilateral input from symmetric vertical canals (in some muscles), cannot be accounted for by the reticulospinal neurons that we studied. Because these characteristics are also not seen in vestibulocollic neurons, they are likely to be the result of the appropriate convergence of vestibular signals in the spinal cord. 7. Pontomedullary reticulospinal neurons seem particularly well suited to play a role in gravity-dependent postural reflexes of neck and limbs.