Otolith-brain stem connectivity: evidence for differential neural activation by vestibular hair cells based on quantification of FOS expression in unilateral labyrinthectomized rats

1. The effects of acute and chronic labyrinthectomies on Fos-defined neuronal activity induced by rotation were determined with the use of quantitative image analysis procedures. Unilateral sodium arsanilate labyrinthectomies (UL) were performed either 24 h (acute) or 2 wk (chronic) before exposure to a 90 min, 2-G centripetal acceleration along the interaural axis that stimulated the intact otolith organs. The results obtained from both acute and chronic UL animals subjected to centripetal acceleration were compared with data obtained from nonrotated UL animals and fully intact, normal animals exposed to centripetal acceleration. Such comparisons allowed the definition of functional projections from the otolith organs of one labyrinth to vestibular related and inferior olivary brain stem nuclei in the rat. 2. The effect of the labyrinthectomy on nonrotated animals was first assessed. After acute UL, asymmetric Fos expression was present in the medial and inferior vestibular nuclei, the prepositus hypoglossi (bilaterally), the ipsilateral (with respect to the side of UL) dorsolateral periaqueductal gray, and the contralateral inferior olivary beta subnucleus, as previously described (Kaufman et al., 1992b). Except for minimal labeling in the contralateral prepositus hypoglossi and the dorsolateral periaqueductal gray, the Fos labeling that was present in the brain stem of acute UL animals was absent in chronic UL animals. Thus Fos neuronal activity appears to define a pattern of brain stem activation associated with the initial events that underlie vestibular compensation. 3. In acute UL rats, which were rotated, the contralateral beta subnucleus of the inferior olive had greater labeling (compared with nonrotated UL animals) when the lesion was away from the axis of rotation. In contrast, the ipsilateral beta subnucleus labeled when the lesion was towards the axis of rotation. Fos expression was observed bilaterally in the prepositus hypoglossi when the lesioned side was oriented toward the axis of rotation but was observed only in the contralateral prepositus nucleus when the lesioned side was oriented away from the axis of rotation. Finally, the dorsomedial cell column of the inferior olive (DMCC) was heavily labeled when the lesioned side was oriented towards the axis of rotation but was unlabeled when the lesioned side was oriented away from the axis of rotation. In acute UL nonrotated animals the DMCC was only lightly labeled. All other brain stem nuclear labeling was similar between the acute UL rotated and nonrotated animals.(ABSTRACT TRUNCATED AT 400 WORDS)

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A rodent model for artificial gravity: VOR adaptation and Fos expression

Journal of Vestibular Research ◽

10.3233/ves-2005-15302 ◽

2005 ◽

Vol 15 (3) ◽

pp. 131-147

Author(s):

Galen Kaufman ◽

Tianxiang Weng ◽

Tara Ruttley

Keyword(s):

Phase Relationship ◽

Cross Coupling ◽

Artificial Gravity ◽

Temporal Association ◽

Half Cycle ◽

Centripetal Acceleration ◽

Vor Adaptation ◽

Fos Expression ◽

Inferior Olivary ◽

And Training

Vestibulo-ocular reflex (VOR) adaptation and brainstem Fos expression as a result of short radius cross-coupling stimuli were investigated to find neural correlates of the inherent Coriolis force asymmetry from an artificial gravity (AG) environment. Head-fixed gerbils (Meriones unguiculatus, N = 79) were exposed, in the dark, to 60–90 minutes of cross-coupled rotations, combinations of pitch (or roll) and yaw rotation, while binocular horizontal, vertical, and torsional eye position were determined using infrared video-oculography. Centripetal acceleration in combination with angular cross-coupling was also studied. Simultaneous sinusoidal rotations in two planes (yaw with roll or pitch) provided a net symmetrical stimulus for the right and left labyrinths. In contrast, a constant velocity yaw rotation during sinusoidal roll or pitch provided the asymmetric stimulus model for AG. We found orthogonally oriented half-cycle VOR gain changes. The results depended on the direction of horizontal rotation during asymmetrical cross-coupling, and other aspects of the stimulus, including the phase relationship between the two rotational inputs, the symmetry of the stimulus, and training. Fos expression also revealed laterality differences in the prepositus and inferior olivary C subnucleus. In contrast the inferior olivary beta and ventrolateral outgrowth were labeled bilaterally. Additional cross-coupling dependent labeling was found in the flocculus, hippocampus, and several cortical regions, including the perirhinal and temporal association cortices. Analyses showed significant differences across the brain regions for several factors (symmetry, rotation velocity and direction, the presence of centripetal acceleration or a visual surround, and training). Finally, animals compensating from a unilateral surgical labyrinthectomy who received multiple cross-coupling training sessions had improved half-cycle VOR gain in the ipsilateral eye with head rotation toward the intact side. We hypothesize that cross-coupling vestibular training can benefit aspects of motor recovery or performance.

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Brain Stem Opioidergic and GABAergic Neurons Mediate the Antinociceptive Effect of Nitrous Oxide in Fischer Rats

Anesthesiology ◽

10.1097/00000542-200310000-00030 ◽

2003 ◽

Vol 99 (4) ◽

pp. 947-954 ◽

Cited By ~ 31

Author(s):

Yoko Ohashi ◽

Tianzhi Guo ◽

Ryo Orii ◽

Mervyn Maze ◽

Masahiko Fujinaga

Keyword(s):

Spinal Cord ◽

Brain Stem ◽

Antinociceptive Effect ◽

Opioid Peptide ◽

Periaqueductal Gray ◽

Gabaergic Neurons ◽

Aminobutyric Acid ◽

Gamma Aminobutyric Acid ◽

Gray Area ◽

Fos Expression

Background Recent studies have revealed that N2O exerts its antinociceptive effect by inducing opioid peptide release in the brain stem, thereby activating the descending noradrenergic inhibitory neurons, which modulate pain processing in the spinal cord. However, the precise neuronal pathways that mediate these events remain to be determined. Methods Using immunohistochemical and behavioral techniques in adult male Fischer rats, the authors studied the involvement of brain stem opioidergic and gamma-aminobutyric acid-mediated (GABAergic) neurons in the N2O-induced antinociceptive effect using discrete microinjections of an opioid receptor antagonist or GABAergic activator into the periaqueductal gray area and pontine noradrenergic nuclei. They used c-Fos expression as an immunohistochemical mark of neuronal activation induced by N2O and the plantar test as the behavioral paradigm for nociception. Results Microinjection of either naloxone (an opioid receptor antagonist) or muscimol (a gamma-aminobutyric acid receptor type A agonist) into the ventrolateral periaqueductal gray area inhibited N2O-induced c-Fos expression in the spinal cord and pontine noradrenergic nuclei, particularly in the A7. Microinjection of either naloxone or muscimol into the A7 nuclei also inhibited N2O-induced c-Fos expression in the spinal cord and the N2O-induced antinociceptive effect by the plantar test. Conclusions These results support the hypothesis that both opioidergic and GABAergic neurons mediate the antinociceptive effect of N2O at the periaqueductal gray area and A7 in the brain stem. The authors postulate that N2O-induced opioid peptide release leads to inhibition of GABAergic neurons via opioid receptors. The descending noradrenergic inhibitory pathways, which are tonically inhibited by these gamma-aminobutyric acid neurons, are thereby activated (disinhibited) and modulate pain processing in the spinal cord.

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Salicylate evokes c-fos expression in the brain stem

Neuroreport ◽

10.1097/00001756-199702100-00029 ◽

1997 ◽

Vol 8 (3) ◽

pp. 725-728 ◽

Cited By ~ 44

Author(s):

E Wallhäusser-Franke

Keyword(s):

Brain Stem ◽

Fos Expression ◽

The Brain

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Suppressive effects of Neiting acupuncture on toothache: an experimental analysis on Fos expression evoked by tooth pulp stimulation in the trigeminal subnucleus pars caudalis and the periaqueductal gray of rats

Neuroscience Research ◽

10.1016/s0168-0102(00)00162-0 ◽

2000 ◽

Vol 38 (4) ◽

pp. 331-339 ◽

Cited By ~ 12

Author(s):

Liu Lian Sheng ◽

Keiji Nishiyama ◽

Takashi Honda ◽

Midori Sugiura ◽

Hiroyuki Yaginuma ◽

...

Keyword(s):

Experimental Analysis ◽

Periaqueductal Gray ◽

Tooth Pulp ◽

Fos Expression

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The embryonic cerebellum contains topographic cues that guide developing inferior olivary axons

Development ◽

10.1242/dev.124.4.861 ◽

1997 ◽

Vol 124 (4) ◽

pp. 861-870 ◽

Cited By ~ 1

Author(s):

A. Chedotal ◽

E. Bloch-Gallego ◽

C. Sotelo

Keyword(s):

Inferior Olive ◽

Positional Information ◽

Original Position ◽

Chick Embryos ◽

In Vitro Experiments ◽

In Vitro System ◽

Target Region ◽

Inferior Olivary ◽

Anteroposterior Polarity

The formation of the olivocerebellar projection is supposed to be regulated by positional information shared between pre- and postsynaptic neurons. However, experimental evidence to support this hypothesis is missing. In the chick, caudal neurons in the inferior olive project to the anterior cerebellum and rostral ones to the posterior cerebellum. We here report in vitro experiments that strongly support the existence of anteroposterior polarity cues in the embryonic cerebellum. We developed an in vitro system that was easily accessible to experimental manipulations. Large hindbrain explants of E7.5-E8 chick embryos, containing the cerebellum and its attached brainstem, were plated and studied using axonal tracing methods. In these cultures, we have shown that the normal anteroposterior topography of the olivocerebellar projection was acquired, even when the cerebellar lamella was detached from the brainstem and placed again in its original position. We also found that, following various experimental rotations of the anteroposterior axis of the cerebellum, the rostromedian olivary neurons still project to the posterior vermis and the caudolateral neurons to the anterior vermis, that now have inverted locations. Thus, the rotation of the target region results in the rotation of the projection. In addition, we have shown that the formation of the projection map could be due to the inability of rostromedian inferior olivary axons to grow in the anterior cerebellum. All these experiments strongly indicate that olivocerebellar fibers recognize within their target region polarity cues that organize their anteroposterior topography, and we suggest that Purkinje cells might carry these cues.

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The effects of focal stimulation in nucleus raphe magnus and periaqueductal gray on intracellularly recorded neurons in spinal laminae I and II

Journal of Neurophysiology ◽

10.1152/jn.1986.56.3.555 ◽

1986 ◽

Vol 56 (3) ◽

pp. 555-571 ◽

Cited By ~ 101

Author(s):

A. R. Light ◽

E. J. Casale ◽

D. M. Menetrey

Keyword(s):

Brain Stem ◽

Periaqueductal Gray ◽

The Other ◽

Descending Pathways ◽

Nucleus Raphe Magnus ◽

Raphe Magnus ◽

Low Threshold ◽

Conductance Increase ◽

Small Conductance ◽

Postsynaptic Mechanism

Single neurons in spinal laminae I and II of cats were recorded intracellularly while stimulating in nucleus raphe magnus (NRM) and periaqueductal gray (PAG) with monopolar tungsten microelectrodes. Brain stem stimulation inhibited about one-half of the nociceptive-specific neurons, whereas the other half was unaffected. Brain stem stimulation inhibited about one-half of the multireceptive neurons, but the other half was excited and then inhibited. Brain stem stimulation inhibited about one-third of the low-threshold neurons, one-half was excited then inhibited, and one-fifth showed no effect. In all classes of neurons, the inhibition was produced by an inhibitory postsynaptic potential (IPSP) that began with a latency of approximately 25 ms and lasted approximately 400 ms following a single stimulus. The IPSP occurred with a small conductance increase and was reversed by hyperpolarizing currents applied to the cell. These data indicate that NRM and PAG modulated laminae I and II neurons via a postsynaptic mechanism. The conduction velocity of this descending pathway was calculated to range from 6.1 to 66.6 m/s with an average of 13.8 m/s. These data also indicate heterogeneity in the pathway, since some neurons were inhibited, whereas other neurons were excited then inhibited by descending stimulation. Finally, these data indicate specificity in these descending pathways since nearly one-half of neurons that had low-threshold inputs were excited by brain stem stimulation, whereas nearly all nociceptive-specific neurons were either inhibited or unaffected.

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Low-Amplitude Oscillations in the Inferior Olive: A Model Based on Electrical Coupling of Neurons With Heterogeneous Channel Densities

Journal of Neurophysiology ◽

10.1152/jn.1997.77.5.2736 ◽

1997 ◽

Vol 77 (5) ◽

pp. 2736-2752 ◽

Cited By ~ 134

Author(s):

Yair Manor ◽

John Rinzel ◽

Idan Segev ◽

Yosef Yarom

Keyword(s):

Inferior Olive ◽

Electrical Coupling ◽

The Other ◽

Sustained Oscillation ◽

Large Coupling ◽

Model Based ◽

Subthreshold Oscillations ◽

Coupling Current ◽

Low Amplitude ◽

Inferior Olivary

Manor, Yair, John Rinzel, Idan Segev, and Yosef Yarom. Low-amplitude oscillations in the inferior olive: a model based on electrical coupling of neurons with heterogeneous channel densities. J. Neurophysiol. 77: 2736–2752, 1997. The mechanism underlying subthreshold oscillations in inferior olivary cells is not known. To study this question, we developed a single-compartment, two-variable, Hodgkin-Huxley-like model for inferior olive neurons. The model consists of a leakage current and a low-threshold calcium current, whose kinetics were experimentally measured in slices. Depending on the maximal calcium and leak conductances, we found that a neuron model's response to current injection could be of four qualitatively different types: always stable, spontaneously oscillating, oscillating with injection of current, and bistable with injection of current. By the use of phase plane techniques, numerical integration, and bifurcation analysis, we subdivided the two-parameter space of channel densities into four regions corresponding to these behavioral types. We further developed, with the use of such techniques, an empirical rule of thumb that characterizes whether two cells when coupled electrically can generate sustained, synchronized oscillations like those observed in inferior olivary cells in slices, of low amplitude (0.1–10 mV) in the frequency range 4–10 Hz. We found that it is not necessary for either cell to be a spontaneous oscillator to obtain a sustained oscillation. On the other hand, two spontaneous oscillators always form an oscillating network when electrically coupled with any arbitrary coupling conductance. In the case of an oscillating pair of electrically coupled nonidentical cells, the coupling current varies periodically and is nonzero even for very large coupling values. The coupling current acts as an equalizing current to reconcile the differences between the two cells' ionic currents. It transiently depolarizes one cell and/or hyperpolarizes the other cell to obtain the regenerative response(s) required for the synchronized oscillation. We suggest that the subthreshold oscillations observed in the inferior olive can emerge from the electrical coupling between neurons with different channel densities, even if the inferior olive nucleus contains no or just a small proportion of spontaneously oscillating neurons.

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