Central vestibular networks in the guinea-pig: functional characterization in the isolated whole brain in vitro

The isolated, in vitro whole brain of guinea-pig was used to assess some of the main physiological and pharmacological properties of the vestibulo-ocular pathways in this species. Extracellular and intracellular recordings were obtained from the vestibular, abducens and oculomotor nuclei, as well as from the abducens and oculomotor nerves, while inputs from the vestibular afferents, the visual pathways and the spinal cord were activated. The three main types of medial vestibular nucleus neurons (A, B and B+LTS), previously described on slices, were also identified in the isolated brain. They had similar membrane properties in both preparations. Eighty-five per cent of cells recorded in the vestibular nucleus responded with monosynaptic, excitatory postsynaptic potentials (latency 1.05-1.9 ms) to stimulation of the ipsilateral vestibular nerve, and were thus identified as second-order vestibular neurons. In addition, stimulation of the contralateral vestibular afferents revealed in most cases a disynaptic or trisynaptic, commissural inhibition. Second-order vestibular neurons displayed in the isolated brain a high degree of variability of their spontaneous activity, as in alert guinea-pigs. Type A neurons always exhibited a regular firing, while type B and B+LTS cells could have very irregular patterns of spontaneous discharge. Thus, type A and type B neurons might correspond, respectively, to the tonic and phasic vestibular neurons described in vivo. The regularity of spontaneous discharge was positively correlated with the amplitude of spike after hyperpolarization, and there was a trend for irregular neurons to be excited from ipsilateral vestibular afferents at shorter latencies than regular units. Synaptic activation could trigger subthreshold plateau potentials and low-threshold spikes in some of the second-order vestibular neurons. As a second step, the pharmacology of the synaptic transmission between primary vestibular afferents and second-order neurons was assessed using specific antagonists of the glutamatergic receptors. Both the synaptic field potentials and excitatory postsynaptic potentials elicited in the medial vestibular nucleus by single shock stimulation of the ipsilateral vestibular nerve were largely or, sometimes, totally blocked by 6-cyano-7-nitroquinoxaline-2,3-dione, indicating a dominating role of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated glutamatergic transmission. The remaining component of the responses was completely or partially suppressed by DL-2-amino-5-phosphonovaleric acid in 35% of the cases, suggesting a concomitant, moderate involvement of N-methyl-D-asparate receptors. In addition, a synaptic response resistant to both antagonists, but sensitive to a zero Ca2+/high Mg(2+)-containing solution, was often observed. Finally, recordings from abducens and oculomotor complexes confirmed the existence in the guinea-pig of strong bilateral, disynaptic excitatory and inhibitory inputs from vestibular afferents to motoneurons of extraocular muscles, which contribute to generation of the vestibulo-ocular reflex. The functional integrity of vestibular-related pathways in the isolated brain was additionally checked by stimulation of the spinal cord and optic tract. Stimulation of the spinal cord evoked, in addition to antidromic responses in the vestibular nucleus, short-latency synaptic responses in both the vestibular nucleus and abducens motoneurons, suggesting possible recruitment of spinal afferents. Activation of visual pathways at the level of the optic chiasm often induced long latency responses in the various structures under study. These results demonstrate that the in vitro isolated brain can be readily used for detailed, functional studies of the neuronal networks underlying gaze and posture control.     

Response of the hypothalamic neurons to stimulation of the vestibular nerve and lateral vestibular nucleus in rabbits

Effects of single, double, and rhythmic stimulation upon hypothalamic neurons responding to the 1st excitatory phase of lateral vestibular nucleus stimulation, were studied. The data obtained show that activation of some hypothalamic neurons following stimulation of the lateral vestibular nucleus has a monosynaptic character. The findings suggest that ascending afferents from the lateral vestibular nucleus to the hypothalamus pass via oligo- as well as polysynaptic pathways.     

Effects of localized pontine lesions on auditory brain-stem evoked potentials and binaural processing in humans

Potassium channels are involved in the control of neuronal excitability by fixing the membrane potential, shaping the action potential, and setting firing rates. Recently, attention has been focused on identifying the factors influencing excitability in second-order auditory and vestibular neurons. Located in the brainstem, second-order auditory and vestibular neurons are sites for convergence of inputs from first-order auditory or vestibular ganglionic cells with other sensory systems and also motor areas. Typically, second-order auditory neurons exhibit two distinct firing patterns in response to depolarization: tonic, with a repetitive firing of action potentials, and phasic, characterized by only one or a few action potentials. In contrast, all mature vestibular second-order neurons fire tonically on depolarization. Already, certain fundamental roles have emerged for potassium currents in these neurons. In mature auditory and vestibular neurons, I(K), the delayed rectifier, is required for the fast repolarization of action potentials. In tonically firing auditory neurons, I(A), the transient outward rectifier, defines the discharge pattern. I(DS), a delayed rectifier-like current distinguished by its low threshold of activation, is found in phasically firing auditory and some developing vestibular neurons where it limits firing to one or a few spikes, and also may contribute to forming short-duration excitatory postsynaptic potential (EPSPs). Also, I(DS) sets the threshold for action potential generation rather high, which may prevent spontaneous discharge in phasically firing cells. During development, there is a gradual acquisition and loss of some potassium conductances, suggesting developmental regulation. As there are similarities in membrane properties of second-order auditory and vestibular neurons, investigations on firing pattern and its underlying mechanisms in one system should help to uncover fundamental properties of the other.     

Spontaneous activity of otolith-related vestibular nuclear neurons in the decerebrate rat

The discharge properties of lateral and descending vestibular neurons responsive to constant velocity off-vertical axis rotations (OVAR) in the clockwise (CW) and counterclockwise (CCW) directions, were studied at the stationary and earth-horizontal position of decerebrate adult rats. From the coefficient of variation (CV), the spontaneous activities of OVAR-responsive neurons were classified into regular and irregular patterns. Of the neurons (n = 36) that showed symmetric and stable bidirectional response sensitivity (delta defined as CW gain over CCW gain) to OVAR (10 degrees tilt), some exhibited progressive phase shift with velocity (1.75-15 degrees/s) while others exhibited stable response phase. Most neurons of the former group (93% or 12/13) showed regular discharge pattern while only 22% (n = 5/23) of the latter group showed such a pattern. Though the phase-stable neurons showed a significantly higher average CV than the phase-shifted neurons, there was no significant difference between the mean spontaneous firing rates of these neurons. The neurons (n = 17) that showed asymmetric and variable delta to OVAR velocity can also be grouped-those that exhibited a greater gain with rotations directed towards the side of recording (I neurons) showed irregular discharge pattern while those that exhibited a greater gain with rotations directed towards the side contralateral to recording (C neurons) showed regular discharge pattern. The I and C neurons also exhibited significant difference in mean firing rates. The relationship between the response characteristics of the OVAR-responsive neurons and their spontaneous activity at the stationary and earth-horizontal position is discussed.     

Cardiopulmonary sympathetic input excites primate cuneothalamic neurons: comparison with spinothalamic tract neurons

Stimulation of cardiopulmonary sympathetic afferent fibers excites thoracic and cervical spinothalamic tract (STT) cells that respond primarily to noxious somatic stimuli. Neurons in dorsal column nuclei respond primarily to innocuous somatic inputs, but noxious stimulation of pelvic viscera activates gracile neurons. The purpose of this study was to compare effects of thoracic visceral input on cuneothalamic and STT neurons. Stellate ganglia of 17 anesthetized monkeys (Macaca fascicularis) were stimulated electrically to activate cardiopulmonary sympathetic afferent fibers. Somatic receptive fields were manipulated with brush, tap, and pinch stimuli. Extracellular discharge rate was recorded for neurons antidromically activated from ventroposterolateral (VPL) thalamus. Stimulation of the ipsilateral stellate ganglion increased activity of 17 of 38 cuneothalamic neurons and of 1 gracilothalamic neuron with an upper body somatic field. Spinal cord transections showed that cardiopulmonary input to cuneothalamic neurons traveled in ipsilateral dorsal column and probably in dorsolateral funiculus. One of eight gracilothalamic neurons with lower body fields was inhibited by cardiopulmonary input, and none were excited. Stimulation of the ipsilateral stellate ganglion increased activity in 10 of 10 T3-T4 STT neurons. Evoked discharge rates, latencies to activation and durations of peristimulus histogram peaks were significantly less for cuneothalamic neurons compared with STT neurons. Furthermore, additional long latency peaks of activity developed in histograms for 6 of 10 STT neurons but never for cuneothalamic neurons. Contralateral cardiopulmonary sympathetic input did not excite cuneothalamic neurons but increased activity of 7 of 10 T3-T4 STT neurons. Most cuneothalamic neurons (24 of 31 cells tested) responded primarily to innocuous somatic stimuli, whereas STT neurons responded primarily or solely to noxious pinch of somatic fields. Neurons that responded to cardiopulmonary input most often had somatic fields located on proximal arm and chest. Results of this study showed that cardiopulmonary input was transmitted in dorsal pathways to cuneate nucleus and then to VPL thalamus and confirmed that STT neurons transmit nociceptive cardiopulmonary input to VPL thalamus. Differences in neuronal responses to noxious stimulation of cardiopulmonary sympathetic afferent fibers suggest that dorsal and ventrolateral pathways to VPL thalamus play different roles in the transmission and integration of nociceptive cardiac information.     

Role of primate medial vestibular nucleus in long-term adaptive plasticity of vestibuloocular reflex

1. Fifteen hundred and thirty cells were recorded in the medial vestibular nucleus (MVN) of alert monkeys whose vestibuloocular reflex (VOR) had been adapted to one of two kinds of spectacles. The "high-gain" sample was recorded from monkeys that had worn 2.0 x telescopic spectacles; the gain of the VOR in the dark (eye velocity divided by head velocity) was greater than 1.5. The "low-gain" sample was recorded from monkeys that had worn goggles providing a visual field that was fixed with respect to the freely turning head; the gain of the VOR was less than 0.4. 2. Cells showing modulation of firing rate related to imposed head velocity were grouped into four categories: pure vestibular (10), vestibular-plus-saccade (10), vestibular-plus-position (10), and vestibular-plus-head/body (24). Sensitivity to head velocity was measured from averaged responses to sinusoidal, 0.4-Hz whole-body oscillation in the horizontal plane. Almost all cells (98%) having increased firing during ipsilateral head rotation received inputs from the horizontal semicircular canals. Conversely, 82% of cells having increased firing during contralateral head rotation received inputs from the vertical canals. 3. There were no statistically significant differences in resting discharge rate, phase shift, or sensitivity to head velocity between the high- and low-gain samples of any of the cell types. Nonetheless, there was a consistent tendency, evident in all the functionally defined cell groups, for the sensitivity to be about 20% greater in the high-gain samples. However, this difference is small by comparison with the fourfold difference in VOR gain. 4. Detailed scrutiny of the response properties of individual cells suggested that the small differences in sensitivity reflect small changes distributed throughout the population, rather than large and potentially significant changes within a small sub-population. 5. Our data indicate that large, adaptive changes in the gain of the VOR are accompanied by only minor changes in the vestibular sensitivity and no changes in the phase shift or resting discharge rates of cells in the MVN. It remains possible that large changes in vestibular sensitivity occurred in cells we did not sample or in subgroups we could not identify. We argue that this is unlikely and that the major changes underlying VOR plasticity occur after the first central synapse in the VOR pathways.     

Polyamine changes in the vestibular nuclei of guinea pigs following labyrinthectomy

Vestibular compensation is a process of behavioral recovery from ocular, motor and postural disorders following unilateral damage to the vestibular end-organ. Although restoration of the normal resting discharge rate in the ipsilateral vestibular nuclei is important in compensation, the biochemical and molecular mechanisms mediating recovery are largely unknown. The ornithine decarboxylase polyamine pathway is activated in the nervous system following axotomy or denervation. The authors postulate that changes in polyamines mediate vestibular compensation. Within 150-micron brain stem coronal section micropunches analyzed by high performance liquid chromatography techniques, the polyamine spermidine was significantly increased in the ipsilateral lateral vestibular nucleus 8 hours following labyrinthectomy in the guinea pig model. Because naturally occurring polyamines modulate excitatory amino acid receptors (N-methyl-D-aspartate [NMDA]) which in turn mediate neurotransmission between primary afferents and second order vestibular neurons, stimulation of polyamine pathways following neural injury may play a critical role in compensation.     

Convergent input from brainstem coincidence detectors onto delay-sensitive neurons in the inferior colliculus

Responses of low-frequency neurons in the inferior colliculus (IC) of anesthetized guinea pigs were studied with binaural beats to assess their mean best interaural phase (BP) to a range of stimulating frequencies. Phase plots (stimulating frequency vs BP) were produced, from which measures of characteristic delay (CD) and characteristic phase (CP) for each neuron were obtained. The CD provides an estimate of the difference in travel time from each ear to coincidence-detector neurons in the brainstem. The CP indicates the mechanism underpinning the coincidence detector responses. A linear phase plot indicates a single, constant delay between the coincidence-detector inputs from the two ears. In more than half (54 of 90) of the neurons, the phase plot was not linear. We hypothesized that neurons with nonlinear phase plots received convergent input from brainstem coincidence detectors with different CDs. Presentation of a second tone with a fixed, unfavorable delay suppressed the response of one input, linearizing the phase plot and revealing other inputs to be relatively simple coincidence detectors. For some neurons with highly complex phase plots, the suppressor tone altered BP values, but did not resolve the nature of the inputs. For neurons with linear phase plots, the suppressor tone either completely abolished their responses or reduced their discharge rate with no change in BP. By selectively suppressing inputs with a second tone, we are able to reveal the nature of underlying binaural inputs to IC neurons, confirming the hypothesis that the complex phase plots of many IC neurons are a result of convergence from simple brainstem coincidence detectors.     

Canal-specific excitation and inhibition of frog second-order vestibular neurons

Second-order vestibular neurons (secondary VNs) were identified in the in vitro frog brain by their monosynaptic excitation following electrical stimulation of the ipsilateral VIIIth nerve. Ipsilateral disynaptic inhibitory postsynaptic potentials were revealed by bath application of the glycine antagonist strychnine or of the gamma-aminobutyric acid-A (GABA(A)) antagonist bicuculline. Ipsilateral disynaptic excitatory postsynaptic potentials (EPSPs) were analyzed as well. The functional organization of convergent monosynaptic and disynaptic excitatory and inhibitory inputs onto secondary VNs was studied by separate electrical stimulation of individual semicircular canal nerves on the ipsilateral side. Most secondary VNs (88%) received a monosynaptic EPSP exclusively from one of the three semicircular canal nerves; fewer secondary VNs (10%) were monosynaptically excited from two semicircular canal nerves; and even fewer secondary VNs (2%) were monosynaptically excited from each of the three semicircular canal nerves. Disynaptic EPSPs were present in the majority of secondary VNs (68%) and originated from the same (homonymous) semicircular canal nerve that activated a monosynaptic EPSP in a given neuron (22%), from one or both of the other two (heteronymous) canal nerves (18%), or from all three canal nerves (28%). Homonymous activation of disynaptic EPSPs prevailed (74%) among those secondary VNs that exhibited disynaptic EPSPs. Disynaptic inhibitory postsynaptic potentials (IPSPs) were mediated in 90% of the tested secondary VNs by glycine, in 76% by GABA, and in 62% by GABA as well as by glycine. These IPSPs were activated almost exclusively from the same semicircular canal nerve that evoked the monosynaptic EPSP in a given secondary VN. Our results demonstrate a canal-specific, modular organization of vestibular nerve afferent fiber inputs onto secondary VNs that consists of a monosynaptic excitation from one semicircular canal nerve followed by disynaptic excitatory and inhibitory inputs originating from the homonymous canal nerve. Excitatory and inhibitory second-order (secondary) vestibular interneurons are envisaged to form side loops that mediate spatially similar but dynamically different signals to secondary vestibular projection neurons. These feedforward side loops are suited to adjust the dynamic response properties of secondary vestibular projection neurons by facilitating or disfacilitating phasic and tonic input components.     

Functional characterization of primary vestibular afferents in the frog

1. In order to more accurately identify the nature of the vestibular input to central neurons, the response properties of single semicircular canal and otolith units in the frog VIIth nerve were studied in curarized preparations. 2. An equation describing the response plane was calculated for each canal on the basis of null point measurements. These results show that the ipsilateral canal planes are orthogonal within 2-5 degrees, and the pairs of right-left synergists are essentially coplanar. A head position of 10-20 degrees maxilla nose up produces optimal horizontal canal and minimal vertical canal activation with horizontal rotation. 3. The frequency response of the horizontal canal was examined in the range 0.025-0.5 Hz. Comparatively shorter phase-lags and a 10 fold greater acceleration gain in this frequency range distinguish the frog from the mammalian species studied. 4. Otolithic responses were tonic, phasic-tonic, and phasic in nature. The preponderance of the latter two groups is stressed (94%). Tonic responses were proportional to the gravitational vector change. Phasic responses were proportional to velocity during transitions in head position and phase-led displacement (30-80%) with sinusoidal acceleration in roll and pitch. 5. Efferent vestibular neurons respond to rotation in the horizontal (usually Type III) as well as vertical planes. Responses in the vertical planes result from canal and/or otolithic input to these neurons indicating that the vestibular efferent system receives extensive multi-labyrinthine convergence.     

Are vocationally trained general practitioners better GPs? A review of research designs and outcomes

Three experiments were conducted on healthy adult bullfrogs (Rana catesbeiana) for the purpose of investigating three characteristics of centrifugal vestibular afferent regeneration after complete transection of the anterior division of the vestibular nerve (AVN). In experiment 1 total fiber count and axon diameter measurements were obtained from the anterior canal nerve at three different time periods and compared with normal. The normal group (n = 3) demonstrated a total fiber count of 1001 +/- 76 (SEM). The early time period (1 to 2 weeks, n = 3) did not completely regenerate as demonstrated by a total fiber count of 282 +/- 23. The intermediate (4 to 6 weeks, n = 3) and late (8 to 16 weeks, n = 3) groups exhibited total fiber counts of 907 +/- 29 and 946 +/- 50, respectively, which were not different from normal (Mann-Whitney U, p > 0.2). Evaluation of fiber diameter distribution of the intermediate and late regenerated nerves revealed a reduction in axon diameter caliber compared with normal (analysis of variance, p < 0.0001). Thus transection of the AVN results in regeneration of all afferents that exhibit a reduction in axon diameter. In experiment 2 fibers innervating the anterior canal crista (ACC) were prelabeled before nerve transection. After the labeling procedure the AVN (n = 3) was sectioned at a location that resulted in denervation of three vestibular receptors: the ACC, horizontal canal cristae (HCC), and utricular macula. After 4 weeks of regeneration the ACC fibers that were prelabeled were observed innervating all three denervated vestibular receptors. This result demonstrated that reinnervation of the peripheral vestibular end organs after AVN transection is a nonspecific process. In experiment 3, 167 regenerated canal afferents were evaluated for functional recovery 16 weeks after transection. Both spontaneous and rotation-induced discharge characteristics were obtained and compared with those obtained from a sample of 254 normal afferents in a previous study (Hoffman LF. Factors affecting the response dynamics of canalicular primary afferent neurons in the bullfrog. St. Petersburg (FL): Association for Research in Otolaryngology; 1989). The mean spontaneous discharge coefficient of variation (CV) +/- standard deviation was 0.60 +/- 0.32 and 0.49 +/- 0.33 for ACC and HCC regenerated afferents, respectively, which did not differ from the normal means of 0.63 +/- 0.33 and 0.54 +/- 0.36 (Mann-Whitney, p > 0.2). Response gains and phases obtained during 0.05 Hz sinusoid rotations at 15 degrees/second maximum horizontal table velocity also demonstrated normal discharge characteristics. The mean phases were -28.2 +/- 25.2 degrees and -55.9 +/- 21.5 degrees for regenerated ACC and HCC afferents, respectively, which were not different from the normal means of -33.77 +/- 24.31 degrees and -58.0 +/- 23.3 degrees (Mann-Whitney U). Furthermore, regenerated afferents exhibited a positive association between phase and CV, which was also true for normal afferents (correlation analysis, p > 0.001). Although the mean gains for regenerated ACC and HCC (7.13 +/- 5.5 and 3.3 +/- 2.4 spikes x sec(-1)/degrees x sec(-2), respectively) afferents were reduced from normal ACC and HCC (14.8 +/- 12.52 and 7.76 +/- 6.58 spikes x sec(-1)/degrees x sec(-2), respectively) afferents (Mann-Whitney U, p > 0.0001), a positive association between gain and CV was also demonstrated by regenerated afferents, as was the case for normal afferents (correlation analysis, p < 0.001). Thus the overall response discharges of regenerated afferents were comparable with normal afferents. Normally, large fibers innervate central regions of the receptor, and smaller fibers innervate the peripheral regions. However, the data from experiments 1 and 2 demonstrate that vestibular nerve regeneration results in a dissociation between the normal topographic organization of fiber size and regional innervation of the receptor epithelium. (ABSTRACT TRUNCATED)     

Uncrossed disynaptic inhibition of second-order vestibular neurons and its interaction with monosynaptic excitation from vestibular nerve afferent fibers in the frog

1. Eighth nerve evoked responses in central vestibular neurons (n = 146) were studied in the isolated brain stem of frogs. Ninety percent of these neurons responded with a monosynaptic excitatory postsynaptic potential (EPSP) after electrical stimulation of the ipsilateral VIIIth nerve. In 5% of these neurons, the EPSP was truncated by a disynaptic inhibitory postsynaptic potential (IPSP), and in 5% of these neurons a pure disynaptic IPSP was evoked. 2. Disynaptic IPSPs superimposed upon apparently pure EPSPs were revealed by bath application of the glycine receptor antagonist strychnine (0.5-5 microM) or of the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline (0.5-2 microM). The evoked EPSP increased in most central vestibular neurons (strychnine: 15 out of 16 neurons; bicuculline 26 out of 29 neurons). At higher stimulus intensities, the evoked spike discharge increased from 2 to 3 spikes before up to 8-10 spikes per electrical pulse during the application of blocking agents. The unmasked disynaptic inhibitory component increased with stimulus intensity to a different extent in different neurons. 3. Lesion studies demonstrated that these inhibitory components were generated ipsilaterally with respect to the recording side. The disynaptic strychnine-sensitive inhibition was mediated by neurons located either in the ventral vestibular nuclear complex (VNC) or in the adjacent reticular formation. The spatial distribution of the disynaptic inhibition was investigated by simultaneous recordings of VIIIth nerve-evoked field potentials at different rostrocaudal locations of the VNC. A significant strychnine-sensitive component was detected in the middle and caudal parts but not in the rostral part of the VNC. A bicuculline-sensitive component was detected in the rostral and in the caudal parts but not in the middle part of the VNC. In view of a similar rostrocaudal distribution of glycineor GABA-immunoreactive neurons in the VNC of frogs, our results suggest that part of the disynaptic inhibition is mediated by local interneurons with a spatially restricted projection area. 4. The monosynaptic EPSP of second-order vestibular neurons was mediated in part by N-methyl-D-aspartate (NMDA) and in part by non-NMDA receptors. The relative contribution of the NMDA receptor-mediated component of the EPSP decreased with stronger stimuli. This negative correlation could have resulted from a preferential activation of NMDA receptors via thick vestibular nerve afferent fibers. Alternatively, the activation of NMDA receptors became disfacilitated at higher stimulus intensities due to the recruitment of disynaptic inhibitory inputs. Comparison of data obtained in the presence and in the absence of these glycine and GABAA receptor blockers indicates a preferential activation of NMDA receptors via larger-diameter vestibular nerve afferent fibers. 5. The kinetics of NMDA receptors (delay, rise time) activated by afferent nerve inputs were relatively fast. These fast kinetics were independent of superimposed IPSPs. The association of these receptors with large-diameter vestibular nerve afferent fibers suggests that fast NMDA receptor kinetics might be matched to the more phasic response dynamics of the large diameter vestibular afferent neurons to natural head accelerations.     

Whole-cell analysis of ionic currents underlying the firing pattern of neurons in the gustatory zone of the nucleus tractus solitarii

1. Previous work from this laboratory has shown that rostral nucleus tractus solitarii (rNTS) neurons can be separated into four different classes on the basis of responses to a current injection paradigm consisting of membrane hyperpolarization immediately followed by a depolarizing pulse. These classes have been termed Group I, II, III, and IV neurons. The regular repetitive firing discharge pattern of Group I cells is changed into an irregular spike train by membrane hyperpolarization. Hyperpolarization of Group II neurons delays the firing discharge induced by depolarization. Hyperpolarization had the least effect on the discharge pattern of Group III neurons. The discharge pattern of Group IV neurons consisted of a short burst of spikes. We used whole-cell recordings and pharmacological channel blockers in an in vitro brain stem slice preparation to determine the ionic basis for the repetitive firing properties of rNTS neurons. 2. Application of 4-aminopyridine (4-AP, 1 mM) decreased input resistance and increased action potential duration in all groups of neurons. However, the discharge pattern of Group I, III, and IV neurons was either unaltered or slightly modified by 4-AP. In contrast the delay in firing of Group II cells induced by hyperpolarization was strongly reduced and in some cases completely suppressed by application of 4-AP. This suggests that a 4-AP-sensitive conductance primarily underlies the firing pattern of Group II cells. 3. Voltage-clamp recordings revealed that the delay in Group II neurons is due to a transient outward potassium current that is partially inactivated around the resting membrane potential. Hyperpolarization removed this inactivation, causing a delay in the firing of the cell. The potassium current was blocked by 4-AP. A similar current was occasionally seen in neurons of the other groups. On the basis of its voltage and pharmacological dependence this current was presumed to be an A-current (IKA). 4. Blockade of calcium currents by a low-calcium (0.5 mM) saline containing 2 mM Co2+ depressed the excitability of rNTS cells. For Group II neurons the delay in firing activity was increased. In the other groups the repetitive firing pattern was suppressed. In addition the amplitude of the afterhyperpolarization occurring after a short train of action potentials was substantially reduced. This indicates that calcium currents (ICa) and calcium-activated potassium currents (IKCa) contribute to the repetitive firing properties of rNTS neurons. 5. In about half of Group I, III, and IV neurons an additional property was found.(ABSTRACT TRUNCATED AT 400 WORDS)     

Imaging techniques in investigation of inflammatory disease of the head and neck

The small-signal linear characteristics of afferent responses from the isolated semicircular canal were described by the use of white-noise rotational acceleration inputs. The results, based on cross-correlation analysis, showed a striking and systematic variation in linear system impulse response characteristics from afferents which innervated different regions of the receptor. Afferents from centrally located nerve bundles innervating the crest region of the crista exhibited an initial maximum response amplitude followed by a rapid decay. In contrast, afferents from extreme rostral and caudal nerve bundles innervating the crista slopes exhibited an initial rise up to a low-amplitude maximum followed by a slower decay. These results imply that the afferents innervating a single canal do not merely carry redundant information concerning current head acceleration, but could be considered an ensemble of specific classes of filters that are tuned individually to specific classes of head movements. On the basis of these considerations, a new hypothesis of matched filter detection was proposed as relevant to information processing and dynamic control in central vestibular pathways.     

Converging inputs to the entorhinal cortex from the piriform cortex and medial septum: facilitation and current source density analysis

Converging inputs to the entorhinal cortex from the piriform cortex and medial septum: facilitation and current source density analysis. J. Neurophysiol. 78: 2602-2615, 1997. The entorhinal cortex receives sensory inputs from the piriform cortex and modulatory inputs from the medial septum. To examine short-term synaptic facilitation effects in these pathways, current source density (CSD) analysis was used first to localize the entorhinal cortex membrane currents, which generate field potentials evoked by stimulation of these afferents. Field potentials were recorded at 50-micron intervals through the medial entorhinal cortex in urethan-anesthetized rats and the one-dimensional CSD was calculated. Piriform cortex stimulation evoked a surface-negative, deep-positive field potential component in the entorhinal cortex with mean onset and peak latencies of 10.4 and 18.4 ms. The component followed brief 100-Hz stimulation, consistent with a monosynaptic response. CSD analysis linked the component to a current sink, which often began in layer I before peaking in layer II. A later, surface-positive field potential component peaked at latencies near 45 ms and was associated with a current source in layer II. Medial septal stimulation evoked positive and negative field potential components which peaked at latencies near 7 and 16 ms, respectively. A weaker and more prolonged surface-negative, deep-positive component peaked at latencies near 25 ms. The early components were generated by currents in the hippocampal formation, and the late surface-negative component was generated by currents in layers II to IV of the entorhinal cortex. Short-term facilitation effects in conscious animals were examined using electrodes chronically implanted near layer II of the entorhinal cortex. Paired-pulse stimulation of the piriform cortex at interpulse intervals of 30 and 40 ms caused the largest facilitation (248%) of responses evoked by the second pulse. Responses evoked by medial septal stimulation also were facilitated maximally (59%) by a piriform cortex conditioning pulse delivered 30-40 ms earlier. Paired pulse stimulation of the medial septum caused the largest facilitation (149%) at intervals of 70 ms, but piriform cortex evoked responses were facilitated maximally (46%) by a septal conditioning pulse 100-200 ms earlier. Frequency potentiation effects were maximal during 12- to 18-Hz stimulation of either the piriform cortex or medial septum. Occlusion tests suggested that piriform cortex and medial septal efferents activate the same neurons. The CSD analysis results show that evoked field potential methods can be used effectively in chronically prepared animals to examine synaptic responses in the converging inputs from the piriform cortex and medial septum to the entorhinal cortex. The short-term potentiation phenomena observed here suggest that low-frequency activity in these pathways during endogenous oscillatory states may enhance entorhinal cortex responsivity to olfactory inputs.     

Differential expression of Fos protein after transection of the rat infraorbital nerve in the trigeminal nucleus caudalis

To determine the effects of nerve injury on Fos expression, temporal and spatial distributions of Fos-positive neurons in the trigeminal nucleus caudalis were examined after tissue injury for isolation of the infraorbital nerve as controls and transection of this nerve as well as noxious chemical stimulation by formalin injection in adult rats. Fos immunoreactivity was markedly elevated in laminae I and II of the only ipsilateral nucleus caudalis 2 h after these surgical procedures and noxious chemical stimulation. The distributions of Fos-positive neurons were restricted rostro-caudally following formalin injection and tissue injury compared to transection of the infraorbital nerve. One day after tissue injury and nerve transection, however, Fos-positive neurons were distributed bilaterally in laminae III and IV extending rostro-caudally and medio-laterally in this nucleus, and this persisted over the 2-week study period. The number of Fos-positive neurons in the side ipsilateral to nerve transection was markedly less than that in the contralateral side whereas positive neurons in the tissue injured rats were distributed symmetrically along the rostro-caudal axis. There was no difference in the contralateral sides between nerve transection and tissue injury groups. The rostro-caudal level showing reduction in Fos expression corresponded roughly to the sites of central termination of the injured nerve in this nucleus, suggesting a role for the primary afferents in the reduction of Fos expression in laminae III and IV neurons of the ipsilateral nucleus caudalis.     

Sensori-sensory afferent conditioning with leg movement: gain control in spinal reflex and ascending paths

Studies are reviewed, predominantly involving healthy humans, on gain changes in spinal reflexes and supraspinal ascending paths during passive and active leg movement. The passive movement research shows that the pathways of H reflexes of the leg and foot are down-regulated as a consequence of movement-elicited discharge from somatosensory receptors, likely muscle spindle primary endings, both ipsi- and contralaterally. Discharge from the conditioning receptors in extensor muscles of the knee and hip appears to lead to presynaptic inhibition evoked over a spinal path, and to long-lasting attenuation when movement stops. The ipsilateral modulation is similar in phase to that seen with active movement. The contralateral conditioning does not phase modulate with passive movement and modulates to the phase of active ipsilateral movement. There are also centrifugal effects onto these pathways during movement. The pathways of the cutaneous reflexes of the human leg also are gain-modulated during active movement. The review summarizes the effects across muscles, across nociceptive and non-nociceptive stimuli and over time elapsed after the stimulus. Some of the gain changes in such reflexes have been associated with central pattern generators. However, the centripetal effect of movement-induced proprioceptive drive awaits exploration in these pathways. Scalp-recorded evoked potentials from rapidly conducting pathways that ascend to the human somatosensory cortex from stimulation sites in the leg also are gain-attenuated in relation to passive movement-elicited discharge of the extensor muscle spindle primary endings. Centrifugal influences due to a requirement for accurate active movement can partially lift the attenuation on the ascending path, both during and before movement. We suggest that a significant role for muscle spindle discharge is to control the gain in Ia pathways from the legs, consequent or prior to their movement. This control can reduce the strength of synaptic input onto target neurons from these kinesthetic receptors, which are powerfully activated by the movement, perhaps to retain the opportunity for target neuron modulation from other control sources.     

Peripheral target specification of synaptic connectivity of muscle spindle sensory neurons with spinal motoneurons

The source of environmental cues determining the central connections of muscle sensory neurons was investigated by manipulating chick embryos so that sensory neurons supplied a duplicate set of dorsal thigh muscles. These neurons projected out ventral nerve pathways and along motor axons that normally project to ventral muscles but their ultimate target tissue was the duplicate set of dorsal muscles. The central connections of these sensory neurons to motoneurons supplying normal dorsal muscles were then determined with intracellular recordings in isolated spinal cord preparations. Sensory neurons supplying individual duplicate dorsal muscles made the same connections as those supplying the corresponding normal dorsal muscles; the pattern of these connections was different than that made by afferents supplying ventral muscles. Sensory neurons thus made synaptic connections appropriate for their target muscle rather than for their more proximal ventral environment. These findings suggest that the target muscle is the source of cues that determine the central connections of the sensory neurons projecting to it. Motoneurons forced to innervate novel muscle received many of the same sensory inputs they would normally receive, suggesting that motoneurons are less influenced by their target tissue than sensory neurons.     

The distribution of afferent neurons in the trigeminal mesencephalic nucleus and the central projection of afferent fibers of the mylohyoid nerve in the rat

Horseradish peroxidase conjugated to wheatgerm agglutinin (HRP:WGA) was injected into the proximal cut ends of three branches of the mylohyoid nerve in rats: the branch to the mylohyoid muscle (BrMh), the branch to the anterior belly of the digastricus muscle (BrDg), and the cutaneous branch (BrCu). HRP-labeled cells were detected in the ipsilateral caudal portion of the trigeminal mesencephalic nucleus (Vmes) and the ipsilateral ventromedial division of the trigeminal motor nucleus, except when HRP:WGA was applied to the BrCu. Morphologically, all labeled Vmes cells were of the pseudounipolar type. Projections of the primary afferents of the BrMh were observed in the ipsilateral trigeminal nucleus caudalis, the upper cervical dorsal horns of laminae I-III, and the dorsolateral recticular formation (Rf), whereas the primary afferents of the BrDg terminated in the ipsilateral trigeminal nucleus principalis and Rf. These observations suggest that the role of the afferent inputs of the mylohyoid muscle differs from that of those of the anterior belly of the digastricus muscle in terms of several functions associated with jaw-closing and infrahyoid muscles.     

Vestibulo-thalamic projections studied with antidromic technique in the cat

The vestibulo-thalamic projection was investigated in anaesthetized cats. Electrical stimulation of posterolateral thalamic areas frequently changed the spontaneous firing pattern of neurons in the vestibular nuclei but only 5% were antidromically invaded. This group was further analysed with regard to types of labyrinthine and somatosensory input; thalamo-projecting neurons in the vestibular nuclei are frequently located in the lateral vestibular nucleus, they receive no monosynaptic inflow from the labyrinth and they often receive convergent vestibular and somatosensory input.