Physiological unloading of cardiopulmonary mechanoreceptors by posture changes does not influence the pressor response to isometric exercise in healthy humans

Summary In recent studies in humans the role of cardiopulmonary baroreflexes in modulating the cardiovascular responses to isometric exercise (somatic pressor reflex) has been investigated by performing static hand-grip exercise during deactivation of cardiopulmonary receptors produced by low levels of lower body negative pressure; however, findings from these studies have not been consistent. The purpose of this study was to investigate whether a more physiological unloading stimulus of cardiopulmonary baroreceptors, obtained by sequentially changing posture, could influence the pressor response to somatic afferent stimulation induced by isometric, exercise. To accomplish this, ten healthy subjects performed a 2-min isometric handgrip (IHG) at 30% maximal voluntary contraction after 10 min of supine rest and, in rapid sequence, after 10 min of sitting and 10 min of standing, at the time when, owing to their transitory nature, the cardiovascular effects, due to arterial baroreceptor intervention should have been minimal. During IHG arterial pressure (BP_a) was continuously and noninvasively measured to quantify accurately the blood pressure response to IHG both in magnitude and time course. Results showed that the pressor response to IHG was not significantly influenced by change in posture, either in magnitude or in time course. The mean arterial pressure increased by 17.4 (SEM 2.5), 18.6 (SEM 1.2) and 17.0 (SEM 1.3) mmHg in supine, sitting and standing [2.3 (SEM 0.3), 2.5 (SEM 0.2) and 2.3 (SEM 0.2) kPa] positions, respectively. Also the heart rate response to IHG was unaffected by change in posture. Most important, the sum of the separate BP_a responses induced by supine IHG and by posture change from supine to sitting (summation of reflexes) was not significantly different from the pressor response observed during sitting IHG (interaction of reflexes). Likewise, the sum of the separate BP_a. responses induced by sitting IHG and by changing postures from sitting to standing was not significantly different from the pressor response to standing IHG. These data indicate that, under physiological conditions, cardiopulmonary baroreflexes do not exert a significant role in modulating the reflex pressor drive from muscles during isometric exercise in healthy humans.     

Influence of stimulation of the head of the caudate nucleus on the activity of postural muscles during realization of an instrumental defensive reflex

A model of instrumental defensive reflexes associated with the maintenance of a specific posture was used in chronic experiments with four dogs to demonstrate the preferential inhibitory influence of preliminary low-frequency stimulation (2 impulses/sec) of the head of the caudate nucleus in the right and left hemispheres on the electromyographic and mechanographic components of the instrumental defensive reflex effecting the reflex motor program. Subjected to the greatest changes were the postural, components of the electromyogram, which permits the postulate as to the importance of the caudate head in the organization of posture. It was shown that the caudate head is bilaterally involved in the prerelease processes preceeding the instrumental response. At the same time, the difficulty of inhibiting the performance of the actual instrumental task- the avoidance of an electric current- was noted during stimulation of the caudate head in a system of instrumental defensive reflexes.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 68, No. 11, pp. 1488–1499, November, 1982.     

Habituation and adaptation of the vestibuloocular reflex: a model of differential control by the vestibulocerebellum

Summary We habituated the dominant time constant of the horizontal vestibuloocular reflex (VOR) of rhesus and cynomolgus monkeys by repeated testing with steps of velocity about a vertical axis and adapted the gain of the VOR by altering visual input with magnifying and reducing lenses. After baseline values were established, the nodulus and ventral uvula of the vestibulocerebellum were ablated in two monkeys, and the effects of nodulouvulectomy and flocculectomy on VOR gain adaptation and habituation were compared. The VOR time constant decreased with repeated testing, rapidly at first and more slowly thereafter. The gain of the VOR was unaffected. Massed trials were more effective than distributed trials in producing habituation. Regardless of the schedule of testing, the VOR time constant never fell below the time constant of the semicircular canals (5 s). This finding indicates that only the slow component of the vestibular response, the component produced by velocity storage, was habituated. In agreement with this, the time constant of optokinetic after-nystagmus (OKAN) was habituated concurrently with the VOR. Average values for VOR habituation were obtained on a per session basis for six animals. The VOR gain was adapted by natural head movements in partially habituated monkeys while they wore ×2.2 magnifying or ×0.5 reducing lenses. Adaptation occurred rapidly and reached about ±30%, similar to values obtained using forced rotation. VOR gain adaptation did not cause additional habituation of the time constant. When the VOR gain was reduced in animals with a long VOR time constant, there were overshoots in eye velocity that peaked at about 6–8 s after the onset or end of constant-velocity rotation. These overshoots occurred at times when the velocity storage integrator would have been maximally activated by semicircular canal input. Since the activity generated in the canals is not altered by visual adaptation, this finding indicates that the gain element that controls rapid changes in eye velocity in the VOR is separate from that which couples afferent input to velocity storage. Nodulouvulectomy caused a prompt and permanent loss of habituation, returning VOR time constants to initial values. VOR gain adaptation, which is lost after flocculectomy, was unaffected by nodulouvulectomy. Flocculectomy did not alter habituation of the VOR or of OKAN. Using a simplified model of the VOR, the decrease in the duration of vestibular nystagmus due to habituation was related to a decrement in the dominant time constant of the velocity storage integrator (1/h ₀). Nodulouvulectomy, which reversed habituation, would be effected by decreasing h ₀, thereby increasing the VOR time constant. Small values of h ₀ would cause velocity storage to approach an ideal integrative process, leading the system to become unstable. By controlling the VOR time constant through habituation, the nodulus and uvula can stabilize the slow component of the VOR. VOR gain adaptation was related to a modification of the direct vestibular path gain g ₁, without altering the coupling to velocity storage g ₀ or its time constant (1/h ₀). The mismatched direct- and indirect-pathway gains simulated the overshoots in the dynamic response to a step in velocity, that were observed experimentally. We conclude that independent distributed elements in the VOR modify its dynamic response, under control of separate parts of the vestibulocerebellum.     

The initial vestibulo-ocular reflex and its visual enhancement and cancellation in humans

The gain (ratio of eye velocity to head velocity) of the initial horizontal vestibulo-ocular reflex (VOR) was calculated in 12 normal subjects over 350 ms during impulsive, unpredictable whole body rotation under three conditions: (1) darkness; (2) visual enhancement of the VOR, while the subjects fixated a stationary target; and (3) visual cancellation of the reflex, while subjects fixated a target that rotated with the head. The gain of the initial 80 ms of compensatory eye movement increased significantly during visual fixation in 5 subjects and decreased during attempted VOR cancellation in 3 subjects, when compared with VOR gain in darkness. Compensatory vestibular smooth eye movements were slowed, becoming curved at the onset of VOR cancellation, at mean latencies ranging from 78 to 149 ms in individual subjects (group mean 128 ms). At about 190 ms, quick phases moved the eyes in the same direction as head and target motion. The subsequent vestibular eye movements were about 50% slower than the initial smooth eye movements, indicating more effective cancellation. Visual enhancement of the VOR can occur prior to the onset of pursuit, providing evidence that fixation and smooth pursuit are distinct ocular motor systems. Visual cancellation of the VOR also begins prior to smooth pursuit initiation and becomes more effective after the latency of smooth pursuit.     

Adaptive modification of the vestibulo-ocular reflex by mental effort in darkness

Summary The vestibulo-ocular reflex (VOR) can be suppressed in darkness if a subject tries to imagine that he looks at a head fixed target. This mental suppression of VOR was used to induce adaptive changes in VOR gam during 3 h of active head oscillations in complete darkness. VOR gain changes were tested by asking the subject to look at a visual target; then passively or actively the head was turned in darkness while the subject fixated the same target. Corrective saccades occurring at the end of the movement when lights were turned on give an elegant measure of VOR gain. Three hours of training induced in 3 subjects a mean of 10.9% and 11.4% decrease of VOR gain for passive and active conditions, respectively. This demonstrates that reflex adaptation can be obtained without external cues, and probably with only an internal reconstruction of target and eye movement.     

Dependence of adaptation of the human vertical angular vestibulo-ocular reflex on gravity

We determined the spatial dependence of adaptive gain changes of the vertical angular vestibulo-ocular reflex (aVOR) on gravity in five human subjects. The gain was decreased for 1 h by sinusoidal oscillation in pitch about a spatial vertical axis in a subject-stationary surround with the head oriented left-side down. Gains were tested by sinusoidal oscillation about a spatial vertical axis while subjects were tilted in 15° increments from left- to right-side down positions through the upright. Changes in gain of the vertical component of the induced eye movements were expressed as a percentage of the preadapted values for the final analysis. Vertical aVOR gain changes were maximal in the position in which the gain had been adapted and declined progressively as subjects were moved from this position. Gain changes were plotted as a function of head orientation and fit with a sine function. The bias level of the fitted sines, i.e., the gravity-independent gain change, was –29±10% (SD). The gains varied around this bias as a function of head position by ±18±6%, which were the gravity-dependent gain changes. The gravity-dependent gain changes induced by only 1 h of adaptation persisted, gradually declining over several days. We conclude that there is a component of the vertical aVOR gain change in humans that is dependent on the head orientation in which the gain was adapted, and that this dependence can persist for substantial periods.     

Canal-otolith interactions in the squirrel monkey vestibulo-ocular reflex and the influence of fixation distance

Natural head movements include angular and linear components of motion. Two classes of vestibulo-ocular reflex (VOR), mediated by the semicircular canals and otoliths (the angular and linear VOR, or AVOR and LVOR, respectively), compensate for head movements and help maintain binocular fixation on targets in space. In this study, AVOR/LVOR interactions were quantified during complex head motion over a broad range of fixation distances at a fixed stimulus frequency of 4.0 Hz. Binocular eye movements were recorded (search-coil technique) in squirrel monkeys while fixation distance (assessed by vergence) was varied using brief presentations of earth-fixed targets at various distances. Stimuli consisted of rotations around an earth-vertical axis and therefore always activated the AVOR. Horizontal and vertical AVORs were assessed when the head was centered over the axis of rotation and oriented upright (UP) and right-side-down (RD), respectively. AVOR gains increased slightly with increasing vergence in darkness, as expected given the small anterior position of the eyes in the head. Combined AVOR/LVOR responses were recorded when subjects were displaced eccentrically from the rotation axis. Eccentric rotations activated the AVOR just as when the head was centered, but added a translational stimulus which generated an LVOR component in response to interaural (IA) or dorsoventral (DV) tangential accelerations, depending on whether the head was UP or RD, respectively. When the head was eccentric and facing nose-out, the AVOR and LVOR produced ocular responses in the same plane and direction (coplanar and synergistic), and response magnitudes increased with increasing vergence. With the head facing nose-in, AVOR and LVOR response components were oppositely directed (coplanar and antagonistic). The AVOR dominated the response when fixation distance was far, and phase was compensatory for head rotation. As fixation distance decreased toward the rotation axis, responses declined to near zero, and when fixation distance approached even closer, the LVOR component dominated and response phase inverted. The same pattern was observed for both horizontal (head UP) and vertical (head RD) responses. The LVOR was recorded directly by rotating subjects eccentrically but in the nose-up (NU) orientation. The AVOR then generated torsional responses to head roll, coexistent with either horizontal or vertical LVOR responses to tangential acceleration when the subject was oriented head-out or right-side-out, respectively. Only the LVOR response components were modulated by vergence. A vectorial analysis of AVOR, LVOR, and combined responses supports the conclusion that AVOR and LVOR response components combine linearly during complex head motion. Received: 27 February 1997 / Accepted: 18 June 1997     

The organization of the vestibulo-oculomotor and trochlear reflex pathways in the rabbit

Summary Intracellular and extracellular responses were recorded with glass micro-electrodes from motoneurons in the IIIrd and IVth cranial nuclei of anesthesized rabbits. Five subgroups of neurons innervating the superior rectus (SR), inferior oblique (IO), inferior rectus (IR), medial rectus (MR), and superior oblique (IVth) extraocular muscles were identified by their antidromic activation from the branches of the IIIrd and IVth cranial nerves. The relative positions of the subgroups thus determined were consistent with the histological data on the rabbit. In the SR, IO, IR, and IVth subgroups the effects of ipsilateral VIIIth nerve stimulation were inhibitory, producing disynaptic IPSPs, while the effects of contralateral VIIIth nerve stimulation were excitatory, producing disynaptic EPSPs. In the MR subgroup, however, a mixture of EPSPs and IPSPs was produced by VIIIth nerve stimulation: this was particularly clear on the ipsilateral side. Sites relaying these VIIIth nerve effects to each of the five subgroups were explored by direct stimulation of various brain stem sites. Stimulation of the superior vestibular nucleus (SV) produced IPSPs monosynaptically in all five subgroups on the ipsilateral side as well as in the contralateral MR subgroup. Stimulation of the medial vestibular nucleus (MV) produced EPSPs monosynaptically in all of the five subgroups on the contralateral side as well as in the ipsilateral MR subgroup. Stimulation of the brachium conjunctivum (BC) also produced EPSPs monosynaptically in the contralateral SR, IO, and IR subgroups. Further, while the recording electrode was placed within each of the five subgroups to observe the extracellular potentials corresponding to the intracellularly recorded IPSPs and EPSPs, the medulla and cerebellum were systematically tracked with a monopolar stimulating electrode. It was thus confirmed that the SV is the sole inhibitory relay site, while excitation is relayed by both the MV and the BC. The origin of the BC pathway was traced to the Y-Group for the IO, to the lateral nucleus of the cerebellum (LN) for the IR, and to both the Y-Group and the LN for the SR subgroup.     

Immunohistochemical localization of substance P and substance P receptor (NK1) in the olivary pretectal nucleus of the rat

The olivary pretectal nucleus (OPN) is the first central nucleus in the pupillary light reflex arc (PLR). Substance P (SP) is a neuropeptide present in the OPN. The present immunohistochemical study, performed at the ultrastructural level, aimed to determine the synaptic localization of SP and SP receptor in the OPN. Three types of SP-positive terminals were found. The most abundant type was of retinal origin, characterized by electron-lucent mitochondria and round vesicles, organized in glomerular structures, making asymmetric synaptic contacts with dendrites, and profiles containing pleomorphic vesicles, also making synaptic contacts with dendrites. The second type of SP-immunoreactive terminal contained electron-dense mitochondria and pleomorphic vesicles. This type made symmetric synaptic contacts and may originate from the ventral part of the lateral geniculate nucleus. The third type of SP-immunoreactive terminals contained electron-dense mitochondria, clear round vesicles, and made an asymmetric synaptic contact. This type originates from the contralateral OPN. SP receptors of the NK1 subtype were revealed to be on dendrites and were part of the glomerular-like arrangement. On account of the present observations, it can be concluded that retinal projections to the OPN use SP as a neuromodulator and synapse on NK1 receptor-containing dendrites of large neurons projecting to the Edinger-Westphal nucleus. Since SP also modulates the parasympathetic component of the PLR, we postulate that SP plays a modulating role in all components of the PLR.