Rhythmic activity of neurons in the rostral ventrolateral medulla of conscious cats: effect of removal of vestibular inputs

Although it is well established that bulbospinal neurons located in the rostral ventrolateral medulla (RVLM) play a pivotal role in regulating sympathetic nerve activity and blood pressure, virtually all neurophysiological studies of this region have been conducted in anesthetized or decerebrate animals. In the present study, we used time- and frequency-domain analyses to characterize the naturally occurring discharges of RVLM neurons in conscious cats. Specifically, we compared their activity to fluctuations in carotid artery blood flow to identify neurons with cardiac-related (CR) activity; we then considered whether neurons with CR activity also had a higher-frequency rhythmic firing pattern. In addition, we ascertained whether the surgical removal of vestibular inputs altered the rhythmic discharge properties of RVLM neurons. Less than 10% of RVLM neurons expressed CR activity, although the likelihood of observing a neuron with CR activity in the RVLM varied between recording sessions, even when tracking occurred in a very limited area and was higher after vestibular inputs were surgically removed. Either a 10-Hz or a 20- to 30-Hz rhythmic discharge pattern coexisted with the CR discharges in some of the RVLM neurons. Additionally, the firing rate of RVLM neurons, including those with CR activity, decreased after vestibular lesions. These findings raise the prospect that RVLM neurons may or may not express rhythmic firing patterns at a particular time due to a variety of influences, including descending projections from higher brain centers and sensory inputs, such as those from the vestibular system.     

Postsynaptic potentials of neck muscle motoneurons evoked by horizontal semicircular canal stimulation in cats

Postsynaptic potentials evoked by stimulation of ipsilateral and contralateral horizontal semicircular canals in motoneurons of muscles tilting and turning the head were investigated in acute experiments on cats anesthetized with chloralose and pentobarbital. Stimulation of the ipsilateral canal evoked EPSPs with latent periods varying from 1.8 to 10.0 msec in 25 of these motoneurons and IPSPs with latent periods varying from 1.9 to 3.9 msec in 10 of them. Calculation of the impulse conduction time from the ipsilateral semicircular canal through Deiters' nucleus to the cervical motoneurons indicates that EPSPs with latent periods of under 3.8 msec may be regarded as disynaptic, and those with latent periods of over 3.8 msec as polysynaptic. Stimulation of the contralateral canal evoked EPSPs with latent periods varying from 1.8 to 6.0 msec in 19 motoneurons and IPSPs with latent periods varying from 3.2 to 3.9 msec in two cells. The possible pathways of transmission of these influences and their functional role are discussed.     

A poroelastic continuum model of the cupula partition and the response dynamics of the vestibular semicircular canal.

Using mixture theory, an axisymmetric continuum model is presented describing the response dynamics of the vestibular semicircular canals to canal-centered head rotation in which the cupula partition is modeled as a poroelastic mixture of interpenetrating solid and fluid constituents. The solid matrix of the cupula is assumed to behave as a linear elastic material, whereas the fluid constituent is assumed to be Newtonian. A regular perturbation analysis of the fluid dynamics in the canal provides a dynamic boundary condition, which acts across the cupula partition. Numerical solution of the coupled system of momentum equations provides the spatio-temporal displacement fields for both the fluid and solid constituents of the cupula. Results indicate that at frequencies above 1 Hz, the fluid constituent is dynamically entrained by the solid matrix such that their motions are bound as if to exist as a single component. The resulting high-frequency response is consistent with the macromechanical response predicted by single-component viscoelastic models of the cupula. Below 1 Hz, the dynamic coupling between the fluid and solid constituents weakens and the transcupular differential pressure is sufficient to force fluid through the mixture with little deformation of the solid matrix. Results are sensitive to the precise value of the cupular permeability. One of the most important distinctions between the present analysis and previous impermeable models of the cupula arises at the micromechanical level in terms of the local fluid flow that is predicted to occur within the cupula and around the ciliary bundles and sensory hair cells. Another important result reveals that the permeation dynamics predicted below 1 Hz gives rise to the same low-frequency macromechanical response as would occur with an impermeable viscoelastic structure having a much greater stiffness. Current estimates of the mechanical stiffness of the cupula, based solely on afferent nerve data, may therefore overestimate the true value intrinsic to the solid matrix by as much as an order of magnitude.     

Simulation of vestibular semicircular canal responses during righting movements of a freely falling cat

The righting maneuver of a freely falling cat was filmed at 1000 pictures per second, and the head position about the roll axis was digitized from each film frame using a graphics input tablet. The head angular velocity and acceleration were computed from the roll axis position trajectory. Head acceleration trajectories approximated two periods of a damped sinusoid at a frequency of 26 Hz. Head acceleration peak amplitudes exceeded 120,000 deg/s². These trajectories were used as stimuli for the horizontal semicircular canals in a computer simulation of first-order afferent responses during the fall. Linear system afferent response dynamics, characterized in a previous study of the cat horizontal canal using pseudorandom rotations, provided the basis for linear predictions of falling cat afferent responses. Results showed predicted single afferent firing rates that exceeded physiological values; and variations in afferent sensitivities and phase were predicted among different neurons. Fast head movement information could be carried by ensemble populations of vestibular neurons, and a phase-locking encoding hypothesis is proposed which accomplishes this. Implications for central program versus peripheral vestibular feedback strategies for motor control during falling are presented and discussed.     

Transformation of angular accelerations by the semicircular canal system of the vestibular apparatus]

Transformation of angular accelerations by the system of three semicircular channels is considered which takes into account mutual influence of vertical channels through a common crus.     

Functional physiology of the semicircular canal ampulla.

Physiology of the semicircular canal (sc) was studied by applying different manipulations to the isolated frog sc. Function of the cupula was investigated by mapping out the mechanical sensitivity on the cupular surface and by removing and replacing the cupula. The cupula was found to be most essential for effective activation of sc receptors. Responses of sc receptors to direct temperature change were studied. The sc nerve discharge increased and decreased due to cool and warm temperature change respectively. This suggests a possibility of direct temperature effect as one of the mechanisms of caloric response.     

Action of vestibular receptors pn the spontaneous afferent activity of an ipsilateral semicircular canal in the frog]

In the frog, the influence of both the part of the efferent system which depends on ipsilateral vestibular inputs and the receptor-receptor fibre system on the afferent activity of semicircular canals is either null or facilitatory. The receptor-receptor fibre system being inhibitory, it seems that the part of the efferent vestibular activity which depends on ipsilateral vestibular inputs is facilitatory, which agrees with previous results.     

Assessment of inertial and gravitational inputs to the vestibular system

A new device for the assessment of instantaneous angular and linear accelerations of the head is presented, which is based on four linear tri-axial accelerometers suitably attached to the head by an helmet. A procedure for reproducible helmet placement and calibration is given. A method is also illustrated to work out the different linear accelerations sensed by the vestibular organs in the left and right labyrinths and the components of the angular acceleration sensed by their semicircular canals. The computation is based on few individual parameters describing the helmet position with respect to external landmarks and on the average internal position and orientation of the vestibula. The purpose is to study the components of internal inertial forces, which represent the primary inputs to the vestibular system devoted to equilibrium and oculomotor control. The system is designed to be of easy application during rehabilitation exercises and in clinical environment during diagnostic and therapeutic manoeuvres. The prototype is tested with simple free movements such as "yes", "no", and gait.     

Peptidergic inputs to sympathetic preganglionic neurons

This paper presents data showing that the sympathetic autonomic areas of the cat thoracolumbar spinal cord contain nerve terminals and fibres with immunoreactivity for at least seven neuropeptides. The distribution in the intermediolateral cell column of the terminals and fibres which contain enkephalin-, neuropeptide Y-, neurotensin-, substance P-, and neurophysin II-like immunoreactivity (ENK, NPY, NT, SP, and NP2, respectively) suggests that these peptides are involved in more generalized functions of the autonomic nervous system. On the other hand, peaks in density of immunoreactivity at certain levels suggest that different levels of influence of sympathetic preganglionic neurons by the various peptides may occur along the length of the thoracolumbar cord. The distribution of terminals and fibres containing somatostatin- and oxytocin-like immunoreactivity (SS and OXY) suggests that these peptides may be part of specific pathways to particular sympathetic preganglionic neurons. The possible sources of the terminals and fibres containing ENK, NPY, NT, SS, and SP include the spinal cord and supraspinal areas, whereas the source of these structures with OXY and NP2 is most likely supraspinal. The data suggest that coexistence of peptides and interactions between structures containing different neuropeptides occur in the spinal autonomic areas. It is speculated that neuropeptides have an important role to play in the regulation of the cardiovascular division of the autonomic nervous system.     

Relations of single semicircular canals to the pontine reticular formation.

The effects of afferent vestibular impulses on single pontine reticular formation units and on a small filament of the IIIrd cranial nerve were recorded with tungsten microelectrodes in 40 curarized guinea pigs. Single-shock and repetitive electrical stimulations were applied by means of stimulating electrodes inserted bilaterally into the perilymphatic space of single ampullae of the anterior and lateral semicircular canals. The reticular unitary response consisted mainly in excitation of the resting discharge rate: most units showed vestibular convergence being affected by separate stimulation of the single four ampullae. the reticular evoked field and unitary potentials accounted for latency values ranging from 0.3 to 2.5 msec. As for the early latencies they can be interpreted as responses mediated by direct vestibulo-reticular fibres. A delimited vestibular projection field in the parameidan pontine reticular formation was not identified.     

Theoretical aspects of cupula deflection in semicircular canal

The deflection of the sensory hairs produced by a given volumetric displacement of endolymph (ΔV) is compared in the two usually-accepted models of the cupula behavior: the watertight hinged flap and the elastic diaphragm. Developing the mathematics of these two models, it appears that the elastic diaphragm engenders a larger deflection of sensory hairs than the hinged flap, the difference being about twice in magnitude. Whatever the model, the angle of the cupular deflection is always proportional to the relative angular displacement of the endolymph during natural stimulations.     

Perspectives for the comprehensive examination of semicircular canal and otolith function.

A review is presented on the three-dimensional aspects of the vestibulo-oculomotor system and the current functional tests for unilateral examination of the individual receptors in the vestibular labyrinth. In the presentation, attention is directed towards the recently developed vestibular tests, which promise a more comprehensive examination of labyrinth function. More explicitly, unilateral tests for the utricle, saccule and the individual semicircular canals are discussed. Caloric irrigation and rotatory testing are widely used as tests for the integrity of the (horizontal) semicircular canals. Little useful diagnosis is made however on the vertical canals, not to mention the otolith organs. A promising approach to the examination of individual semicircular canal function has been described. This involves the perception of self-rotation in each of the planes of the semicircular canals. The patient/subject is rotated by an arbitrary amount on a standard Barany chair and then required to return the chair to its original position, by joystick control of the chair velocity. In order to test the vertical canals, the head of the subject/patient is positioned so that the plane of each canal lies in the plane of rotation. A promising unilateral test of saccular function involves the use of vestibular evoked myogenic potentials. Here it has been demonstrated that the saccules can be activated using brief, high-intensity acoustic clicks. The myogenic potential is measured using surface electrodes over the sternocleidomastoid muscles. Initial data from patients has indicated that the test is specific for unilateral saccule disorders. The unilateral test of utricle function is based on the eccentric displacement profile. Thus, eccentric displacement of the head to 3.5 cm during constant velocity rotation about the earth-vertical axis generates an adequate unilateral stimulation of the otolith organ, without involving the semicircular canals. This paradigm has also proved efficient in localizing peripheral otolith dysfunction by means of SVV estimation. This represents a novel test of otolith function that can be easily integrated into routine clinical testing. In contrast to the otolith-ocular response, the subjective visual vertical also reflects the processing of otolithic information in the higher brain centres (thalamus, vestibular cortex). Exploitation of the two complementary approaches therefore provides useful information for both experimental and clinical scientists. Of direct interest is the finding that testing with the subject rotating on-centre is sufficient to localize peripheral otolith dysfunction by means of SVV estimation. This represents a novel test of otolith function that can be easily integrated into routine clinical testing. In addition to caloric testing, which has remained the classical unilateral test of vestibular function, the newly developed tests should improve the differential diagnosis of vestibular disorders.     

An analysis of the mechanical forces in each semicircular canal of the cat under single and combined rotations

The vector equation for the general motion of a body in an inertial system is used to analyze the accelerations in the semicircular canals of the cat when the head undergoes rotation about a vertical axis only, rotation about the naso-occipital axis only, and both rotations simultaneously. The corresponding mean forces and mean pressures in the endolymph are calculated by means of a closed line integral along each canal circumference. The importance of the area of the semicircular canal and of its orientation in space become evident. One can see through this mathematical analysis that the input pattern received by the labyrinthine system depends on a set of well-specified geometrical and mechanical conditions, which must be precisely evaluated in order to interpret the nystagmic outputs.     

Olfactory inputs to hypothalamic neurons controlling reproduction and fertility

In order to gain insight into sensory processing modulating reproductive behavioral and endocrine changes, we have aimed at identifying afferent pathways to neurons synthesizing luteinizing hormone-releasing hormone (LHRH, also known as gonadotropin-releasing hormone [GnRH]), a key neurohormone of reproduction. Injection of conditional pseudorabies virus into the brain of an LHRH::CRE mouse line led to the identification of neuronal networks connected to LHRH neurons. Remarkably, and in contrast to established notions on the nature of LHRH neuronal inputs, our data identify major olfactory projection pathways originating from a discrete population of olfactory sensory neurons but fail to document any synaptic connectivity with the vomeronasal system. Accordingly, chemosensory modulation of LHRH neuronal activity and mating behavior are dramatically impaired in absence of olfactory function, while they appear unaffected in mouse mutants lacking vomeronasal signaling. Further visualization of afferents to LHRH neurons across the brain offers a unique opportunity to uncover complex polysynaptic circuits modulating reproduction and fertility.     

Effect of removal of the cerebellum on vestibular responses of neurons in various descending tracts in cats

Responses of vestibulo-, reticulo-, and rubro-spinal neurons of decerebrate cats to tilting in the frontal plane were investigated. In cats with an intact cerebellum only dynamic responses, i.e., responses during movement (with a small after-effect), were observed. In decerebellate cats responses of the rubro-spinal neurons were absent, and those of the reticulo-spinal neurons were greatly reduced. Dynamic responses of vestibulo-spinal neurons also were considerably reduced, but static responses appeared in many neurons.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 4, No. 3, pp. 303–310, May–June, 1972.     

Evolution of locomotion in Anthropoidea: the semicircular canal evidence

Our understanding of locomotor evolution in anthropoid primates has been limited to those taxa for which good postcranial fossil material and appropriate modern analogues are available. We report the results of an analysis of semicircular canal size variation in 16 fossil anthropoid species dating from the Late Eocene to the Late Miocene, and use these data to reconstruct evolutionary changes in locomotor adaptations in anthropoid primates over the last 35 Ma. Phylogenetically informed regression analyses of semicircular canal size reveal three important aspects of anthropoid locomotor evolution: (i) the earliest anthropoid primates engaged in relatively slow locomotor behaviours, suggesting that this was the basal anthropoid pattern; (ii) platyrrhines from the Miocene of South America were relatively agile compared with earlier anthropoids; and (iii) while the last common ancestor of cercopithecoids and hominoids likely was relatively slow like earlier stem catarrhines, the results suggest that the basal crown catarrhine may have been a relatively agile animal. The latter scenario would indicate that hominoids of the later Miocene secondarily derived their relatively slow locomotor repertoires.