Response of guinea pig vestibular nucleus neurons to clicks

Responses of single neurons in the vestibular nuclei to clicks were studied by extracellular recording in anaesthetised guinea pigs. Eighty-four neurons in the ipsilateral vestibular nuclei were activated with an average latency of 1.75±0.30 ms, which is about 0.9 ms longer than the mean latency of activation of click-sensitive vestibular afferents to intense clicks. The threshold of clicks for evoking the response of these neurons was around 70 dB above the auditory brainstem response threshold. Earlier studies have indicated that click-sensitive vestibular afferents are tilt-sensitive and likely to originate from saccular receptors, and in the present study nine of the click-sensitive vestibular nucleus neurons were tilt-sensitive, suggesting that these central neurons receive monosynaptic input from the corresponding saccular afferents. Recording sites were marked by means of iontophoretic injection of FCF green dye; they were located in the lateral portion of the descending vestibular nucleus and the caudal and ventral regions of the lateral vestibular nucleus.     

Oscillatory and intrinsic membrane properties of guinea pig nucleus prepositus hypoglossi neurons in vitro

Numerous models of the oculomotor neuronal integrator located in the prepositus hypoglossi nucleus (PHN) involve both highly tuned recurrent networks and intrinsic neuronal properties; however, there is little experimental evidence for the relative role of these two mechanisms. The experiments reported here show that all PHN neurons (PHNn) show marked phasic behavior, which is highly oscillatory in approximately 25% of the population. The behavior of this subset of PHNn, referred to as type D PHNn, is clearly different from that of the medial vestibular nucleus neurons, which transmit the bulk of head velocity-related sensory vestibular inputs without integrating them. We have investigated the firing and biophysical properties of PHNn and developed data-based realistic neuronal models to quantitatively illustrate that their active conductances can produce the oscillatory behavior. Although some individual type D PHNn are able to show some features of mathematical integration, the lack of robustness of this behavior strongly suggests that additional network interactions, likely involving all types of PHNn, are essential for the neuronal integrator. Furthermore, the relationship between the impulse activity and membrane potential of type D PHNn is highly nonlinear and frequency-dependent, even for relatively small-amplitude responses. These results suggest that some of the synaptic input to type D PHNn is likely to evoke oscillatory responses that will be nonlinearly amplified as the spike discharge rate increases. It would appear that the PHNn have specific intrinsic properties that, in conjunction with network interconnections, enhance the persistent neural activity needed for their function.     

Activity of lateral vestibular nucleus neurons during locomotion in the decerebrate Guinea pig

Summary The influence of locomotor activity upon neurons in the lateral vestibular nucleus was investigated in precollicularly-postmamillary decerebrate guinea pigs. Out of 95 recorded neurons, 24 were identified as vestibulospinal and 71 had no descending projections. Locomotor activity occurred either spontaneously or was prompted by electrical stimulation of the mesencephalic locomotor region. Natural vestibular stimulation was supplied by tilting the animal about its longitudinal axis. Locomotor rhythmic limb muscle activity was accompanied by an increase in the firing frequency in the vast majority of investigated neurons. The increase in frequency was observed at the beginning of ipsilateral forelimb extensor muscle activity. Only in a few non-vestibulospinal neurons was the spontaneous activity depressed during locomotion. An increase in evoked responses was observed in almost all vestibulospinal neurons and in two thirds of the neurons without descending projections. A decrease in evoked responses was observed in one quarter of non-vestibulospinal neurons. During locomotion, the mean and maximal frequencies of evoked neuronal impulse activity changed, but the phase lag of these changes was not altered significantly. The results suggest an enhancement of vestibulospinal influences during locomotion, thus providing a high level of tonus in antigravitational muscles. This is interpreted as a mechanism to ensure that equilibrium is maintained during motion in different gaits and postures.     

Resonance of spike discharge modulation in neurons of the guinea pig medial vestibular nucleus

The modulation of action potential discharge rates is an important aspect of neuronal information processing. In these experiments, we have attempted to determine how effectively spike discharge modulation reflects changes in the membrane potential in central vestibular neurons. We have measured how their spike discharge rate was modulated by various current inputs to obtain neuronal transfer functions. Differences in the modulation of spiking rates were observed between neurons with a single, prominent after hyperpolarization (AHP, type A neurons) and cells with more complex AHPs (type B neurons). The spike discharge modulation amplitudes increased with the frequency of the current stimulus, which was quantitatively described by a neuronal model that showed a resonance peak >10 Hz. Modeling of the resonance peak required two putative potassium conductances whose properties had to be markedly dependent on the level of the membrane potential. At low frequencies (< or =0.4 Hz), the gain or magnitude functions of type A and B discharge rates were similar relative to the current input. However, resting input resistances obtained from the ratio of the membrane potential and current were lower in type B compared with type A cells, presumably due to a higher level of active potassium conductances at rest. The lower input resistance of type B neurons was compensated by a twofold greater sensitivity of their firing rate to changes in membrane potential, which suggests that synaptic inputs on their dendritic processes would be more efficacious. This increased sensitivity is also reflected in a greater ability of type B neurons to synchronize with low-amplitude sinusoidal current inputs, and in addition, their responses to steep slope ramp stimulation are enhanced over the more linear behavior of type A neurons. This behavior suggests that the type B MVNn are moderately tuned active filters that promote high-frequency responses and that type A neurons are like low-pass filters that are well suited for the resting tonic activity of the vestibular system. However, the more sensitive and phasic type B neurons contribute to both low- and high-frequency control as well as signal detection and would amplify the contribution of both irregular and regular primary afferents at high frequencies.     

Calcium-activated hyperpolarizations in neurons of the mediolateral part of the lateral septum: intracellular studies from guinea pig brain slices

Intracellular recordings were used to study the afterpotentials that followed a single spike and trains of spikes in class A neurons (n=85) of the mediolateral part of the lateral septum (LSml) of the guinea pig in in vitro slices. Following a single spike, LSml neurons (n=56) developed a slow afterhyperpolarization (sAHP), called early sAHP. These sAHP did not sum; other LSml neurons (n=8) showed a depolarizing afterpotential (DAP) that summed. Twenty-one neurons did not exhibit an afterpotential. Following a train of spikes, LSml neurons (n=79) developed a long-lasting sAHP, called late sAHP; these sAHP summed. Both the DAP and the early and late sAHP were markedly suppressed in amplitude by addition of Co²⁺ but persisted in the presence of tetrodotoxin (TTX). Increase in external K⁺ markedly depressed the early and late sAHP. Apamin and d-tubocurarine selectively blocked early sAHP, with no effect on late sAHP. These results indicate that the early and late sAHP are mainly generated by an activation of two types of Ca²⁺-dependent K⁺ conductances, with different time courses and pharmacological properties. In LSml neurons, late sAHP mediates the long-term adaptation of repetitive firing.     

Evidence for inhibitory amino acid receptors on guinea pig medial vestibular nucleus neurons in vitro

There is little evidence to indicate the identity of the inhibitory receptors which mediate inhibitory interaction between the two medial vestibular nuclei ('brainstem commissural inhibition'). In the present study we tested the hypothesis that medial vestibular nucleus (MVN) neurons have gamma-aminobutyric acid (GABA) or glycine receptors by recording from single MVN neurons in isolated guinea pig MVN slices maintained in vitro while superfusing with GABA (10(-8) M) and the non-competitive GABAA antagonist picrotoxin (10(-6) M or 2 x 10(-6) M), or glycine (10(-6) M) and the competitive glycine antagonist strychnine (10(-6) M). Forty-four % (16/36) of the neurons tested with GABA showed a decrease in firing; in 7 out of 8 cases in which a decrease in firing occurred, the addition of the antagonist picrotoxin completely blocked the effect of the GABA alone. Fifty % (7/14) of the neurons tested with glycine showed a decrease in firing; in 4 out of 6 cases where a decrease occurred, the addition of the antagonist strychnine completely blocked the effect of the glycine alone. In one case only did a cell respond both to GABA and glycine (8 neurons tested with both). These results are consistent with the hypothesis that some MVN neurons have GABA or glycine receptors (but in most cases not both), which may mediate brainstem commissural inhibition.     

Responses of guinea pig primary vestibular neurons to clicks

Responses of single neurons in the vestibular nerve to high-intensity clicks were studied by extracellular recording in anaesthetised guinea pigs. One hundred and two neurons in the posterior division of the superior branch or in the inferior branch of the vestibular nerve were activated at short latency by intense clicks. The latency of activation was short (median 0.9 ms) and the threshold was high: the click intensity for evoking the response of these cells was around 60 dB above the auditory brainstem response threshold. Animals were tilted and rotated to identify physiologically the sensory region of the labyrinth from which the activated neurons originated. Seventeen neurons responded to static tilt as well as clicks. These results show that vestibular receptors, probably the otoliths, respond to clicks at intensities corresponding to those used in a new clinical test of the vestibulo-collic pathway.     

Membrane properties and synaptic responses of the guinea pig nucleus accumbens neurons in vitro

1. The membrane properties and synaptic responses of guinea pig nucleus accumbens neurons in vitro were studied with intracellular recording methods. 2. The population of neurons could be divided into groups of low (20-60 M omega, average 46.5 M omega) and high (60-180 M omega, average 96.5 M omega) input resistance. The resting membrane potential in both groups was approximately -70 mV. 3. Other membrane properties were quite similar in both groups. Inward rectification occurred at potentials more negative than -80 mV; this was blocked by Cs+ (2 mM). Membrane potential oscillations were observed at potentials between -65 and -55 mV; these were blocked by tetrodotoxin (TTX, 0.5 microM). Outward rectification occurred at potentials less negative than -45 mV; this was depressed by tetraethylammonium (TEA, 10 mM). 4. Action potentials elicited by small depolarizing current pulses (2-5 ms, 0.3-0.5 nA) were approximately 95 mV in amplitude and 1.0 ms in duration. The afterhyperpolarization following each action potential was less than 30 ms in duration, and no accommodation of action-potential discharge was seen at frequencies up to 40 Hz. The action potentials were reversibly blocked by TTX (0.3 microM). In addition, TTX-insensitive, Ca2+-dependent spikes were evoked by passing larger and more prolonged current pulses (greater than 40 ms, greater than 0.5 nA) across the membrane. 5. Focal electrical stimulation of the slice surface with low intensity (1 ms, less than 10 V) elicited excitatory postsynaptic potentials (EPSPs) in neurons of both high- and low-resistance groups. The reversal potential (+10.2 mV) for the EPSPs was close to the reversal potential (+7.7 mV) of the responses to glutamate applied in the superfusing solution. The N-methyl-D-aspartic acid (NMDA) receptor antagonists, D-alpha-aminoadipic acid (1 mM) and DL-2-amino-5-phosphonovaleric acid (DL-APV, 250 microM), reversibly depressed the EPSP; the glutamate uptake inhibitor, L-aspartic acid-beta-hydroxamate (50 microM), or removal of Mg2+ from the superfusate, augmented the EPSP. 6. When the intensity of the focal stimulus was increased (1 ms, greater than or equal to 10 V), a second larger depolarizing response (duration, 800 ms to 2 s) could be evoked in addition to the smoothly graded EPSP. This was seen only in cells of the high-resistance group (90-130 M omega).(ABSTRACT TRUNCATED AT 400 WORDS)     

Electrotonic coupling between neurons in the rat lateral vestibular nucleus

Summary Correlation of morphological and electrophysiological data strongly suggest that in rat, the giant cells of the lateral vestibular nucleus (L.V.N.) are electrotonically coupled. 1. in addition to active zones large terminals synapsing on the perikaryon and/or the main dendritic trunk of the cells bear gap junctions which are interpreted as low electrical resistance pathways between neurons. 2. electrical activity of the giant cells was recorded intracellularly as the vestibulo-spinal tract was stimulated. Graded antidromic stimulation produced graded antidromic depolarizations (G.A.Ds) in 69% of cells with high threshold axons. 3. the latency of the G.A.Ds was too short to allow for chemical transmission through afferents or recurrent collaterals. 4. collision experiments demonstrated that directly evoked spikes blocked the antidromic spikes but did not block the G.A.Ds which thus were accounted for by activation of cells others than the impaled ones. 5. lesion experiments indicated that afferent fibers from the spinal cord terminate exclusively in the dorsal part of the L.V.N. Since G.A.Ds were recorded all throughout the nucleus, they were not excitatory post synaptic potentials (EPSPs) from spinal afferents. 6. when the strength of the spinal cord stimulation was increased EPSPs were also generated but they were distinct from the G.A.Ds by their latencies, time course and maximum amplitude. 7. since no direct contact is observed between neurons it is inferred that, as in other documented cases, coupling between giant cells is mediated by way of presynaptic fibers.Maitre de Recherches à l'INSERM.     

Immunohistochemical evidence for GABAergic cell bodies in the medial nucleus of the trapezoid body and in the lateral vestibular nucleus in the guinea pig brainstem

The presence of gamma-aminobutyric acid (GABA) in two brainstem nuclei is demonstrated by using a pre-embedding immunohistochemical procedure followed by staining intensification. Firstly, immunoreactivity was found in numerous cell bodies and profiles of the medial nucleus of the trapezoid body (MNTB). Secondly, numerous neurons including giant Deiters' cells, terminals and fibers were strongly labelled within the lateral vestibular nucleus (LVN). These observations suggest that the inhibitory part of the efferent innervation of outer hair cells in the cochlea can originate from the MNTB, and that GABAergic neurons in the LVN may contribute to information processing within this nucleus.     

Responses of hypothalamic neurons to stimulation of the vestibular nerve and lateral vestibular nucleus in the rabbit

Acute experiments were performed on rabbits to study the responses of neurons in the anterior, ventromedial, and posterior nuclei of the hypothalamus to single, paired, and rhythmic stimulation of the vestibular nerve and lateral vestibular nucleus of Deiters. The data obtained showed that neurons of the posterior nucleus of the hypothalamus were the most sensitive. Three types of response were seen from hypothalamic neurons, with short, long, and intermediate latent periods. This provides evidence that ascending afferent spike activity from the lateral vestibular nucleus of Deiters to the hypothalamus is mediated by mono-, oligo-, and polysynaptic pathways. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 83, No. 11-12, pp. 49–56, November–December, 1997.     

Intrinsic membrane properties of central vestibular neurons in rodents

Numerous studies in rodents have shown that the functional efficacy of several neurotransmitter receptors and the intrinsic membrane excitability of central vestibular neurons, as well as the organization of synaptic connections within and between vestibular nuclei can be modified during postnatal development, after a lesion of peripheral vestibular organs or in vestibular-deficient mutant animals. This review mainly focuses on the intrinsic membrane properties of neurons of the medial vestibular nuclei of rodents, their postnatal maturation, and changes following experimental or congenital alterations in vestibular inputs. It also presents the concomitant modifications in the distribution of these neurons into different neuron types, which has been based on their membrane properties in relation to their anatomical, biochemical, or functional properties. The main points discussed in this review are that (1) the intrinsic membrane properties can be used to distinguish between two dominant types of neurons, (2) the system remains plastic throughout the whole life of the animal, and finally, (3) the intracellular calcium concentration has a major effect on the intrinsic membrane properties of central vestibular neurons.     

Muscarinic modulation of acetylcholine release from slices of guinea pig nucleus basalis magnocellularis

Spontaneous and electrically evoked endogenous acetylcholine release and [³H]-choline efflux from slices of guinea pig nucleus basalis magnocellularis (nbM) were studied. Tetrodotoxin reduced the spontaneous endogenous release by 55%, while the Ca²⁺-free medium reduced it by about 30%. Evoked [³H]-choline efflux was Na⁺ and Ca²⁺ dependent and frequency related. Physostigmine, 30 μM, nearly halved the stimulation-evoked efflux; atropine, 0.15 μM, not only antagonized, but even reversed this effect into facilitation. Pirenzepine, 1 μM, and AFDX 116, 1 μM, were less effective than atropine, and reversed the inhibitory effect of physostigmine only when applied together. 4-DAMP, 0.01 μM, was ineffective. These findings indicate that acetylcholine release in guinea pig nbM slices is inhibited by the cooperation of muscarinic autoreceptors, possibly belonging to the M₁ and M₂ subclasses.     

Projection of primary vestibular afferent fibres to the cochlear nucleus in the guinea pig

After tracing the superior branch of the vestibular nerve and the macula sacculi by means of the neuronal tracers horseradish peroxidase (HRP) and wheat germ conjugated horseradish peroxidase (WGA-HRP), a conspicuous fibre bundle running into the cochlear nucleus could be observed. The HRP-labeled axons travel caudally through the descending vestibular nucleus, enter the cochlear nucleus at a level caudal to subgroup y and terminate at cells situated between the dorsal and posteroventral cochlear nucleus. Considering recent electrophysiological studies, it is reasonable to imply that these fibres are involved with the transduction of acoustic stimuli.     

Electrically evoked responses in onset chopper neurons in guinea pig cochlear nucleus

Extracellular recordings were obtained from single cochlear nucleus neurons in guinea pigs anesthetized with Nembutal and Hypnorm. Neurons were classified by their spontaneous firing rates and responses to acoustic stimuli. In addition, electrical shocks were applied to the midline at the level of the IVth ventricle and spike responses were recorded. Spikes were evoked by shocks only in neurons that were classified as onset choppers (O(c)). The shock-evoked spikes could be extinguished by acoustically evoked action potentials in the same neurons. In roughly 30% of the sample of O(c) neurons, quantitative aspects of the timing of this extinction were not compatible with the shock-evoked spike being antidromically conducted from O(c) output axons. Together with the presence of temporal jitter at high shock rates, the data suggest the possibility that at least some of the shock-evoked spikes may be generated by excitatory synaptic input to the O(c) neurons, most likely from the collaterals of the medial olivocochlear system (MOCS), whose axons pass close to the floor of the IVth ventricle. This excitatory synaptic input may operate to modulate the activity of O(c) neurons in addition to MOCS actions in the auditory periphery.     

Functional properties of a slowly inactivating potassium current in guinea pig dorsal lateral geniculate relay neurons.

1. The time- and voltage-dependent properties of a slowly inactivating and depolarization-activated potassium current and the functional consequences of its activation was investigated with current and single-electrode voltage-clamp techniques applied to guinea pig dorsal lateral geniculate neurons maintained as a slice in vitro. 2. In current clamp, application of a step depolarization to near firing threshold resulted in a slowly rising membrane potential that took up to 10 s to reach steady state and firing threshold. In voltage clamp, step depolarization of the membrane potential to values positive to approximately -65 mV resulted in the rapid activation followed by slow inactivation of an outward current. In both cases the sudden depolarization was associated with a large increase in membrane conductance, which gradually lessened in parallel with the slow depolarization in current clamp or with the decrease in outward current in voltage clamp. 3. The time course of inactivation of the outward current, which we refer to as IAs, was well fitted by a two-exponential function with time constants of 96 and 2,255 ms, suggesting the presence of a fast and slow phase of inactivation. The activation threshold for IAs was about -65 to -60 mV, whereas inactivation was incomplete even at -50 mV, suggesting the presence of a substantial "window" current. The time course of removal of inactivation of IAs at -85 to -100 mV was well fitted by a single exponential function with time constant of 91 ms. 4. IAs appears to be mediated by K+. Increasing [K+]o from 2.5 to 10 mM resulted in a reduction in amplitude of IAs, whereas changing from 10 to 2.5 mM [K+]o enhanced this current. Intracellular injection of Cs+ resulted in an abolition of IAs, whereas extracellular application of Ba2+ resulted in a large decrease in the apparent input conductance but relatively little reduction of IAs. 5. Both phases of inactivation of the transient outward current were completely blocked by low doses (100 microM) of 4-aminopyridine (4-AP), but not by extracellular application of Cs+, tetraethylammonium (TEA), tetrodotoxin (TTX), or after block of transmembrane Ca2+ currents. Local application of 4-AP to neurons depolarized to near firing threshold resulted in depolarization associated with a decrease in apparent input conductance, thereby confirming the presence of a window current.4+ this bias against depolarizing inputs.(ABSTRACT TRUNCATED AT 400 WORDS)     

Electrophysiological evidence for cholinoceptive neurons in the medial vestibular nucleus: studies on rat brain stem in vitro

Electrophysiological studies were performed to determine whether or not cholinoceptive neurons are present in the rat medial vestibular nucleus (MVN) using brainstem slice preparations. Fifty-three MVN neurons, whose activities were extracellularly recorded, fired spikes spontaneously and regularly with an interspike interval of 180 +/- 27 ms (mean +/- S.E.M.) and a coefficient of variation of 0.11 +/- 0.02. Intracellularly recorded neurons also exhibited similar spontaneous and regular generation of action potentials. Carbachol dose-dependently increased the spontaneous firing, although the firing rate was decreased in a few neurons. The addition of atropine reduced the firing rate, and dose-dependently attenuated the carbachol-induced excitation of the neurons. In a low Ca2+ and high Mg2+ medium, carbachol also increased the firing rate. These results indicate that the MVN contains neurons with spontaneous and regular firing, and that the excitability of these neurons is regulated by a cholinergic muscarinic mechanism.