On the role of vestibulo-ocular reflex plasticity in recovery after unilateral peripheral vestibular lesions

Summary Although adaptive plasticity is a wellknown feature of the vestibulo-ocular reflex (VOR), deficits in VOR performance after unilateral labyrinthectomy are poorly compensated in a large percentage of cats. To assess whether VOR plastic capabilities are affected by labyrinthectomy, forced oscillation in front of a patterned surround was imposed in unilaterally labyrinthectomized cats. This experimental paradigm has been shown to be very effective in inducing adaptive VOR gain changes in intact animals. We demonstrate that plasticity of VOR gain is still present both in acute and chronic stages following vestibular lesions. By contrast, forced oscillation did not significantly alter the lesion-induced asymmetry of responses. We conclude that VOR gain control mechanisms are not used to their fullest possible extent in a large percentage of animals suffering unilateral vestibular damage.Supported by grants nos. 3.228.82 and 3.403.83 from the Swiss National Science Foundation and Dr. Erik Slack-Gyr FoundationProf. Precht died on March 12, 1985     

Effects of acute hypotension on expression of cFos-like protein in the vestibular nuclei of rats

The expression and regional distribution of cFos protein, which is an oncogene product and metabolic marker of neural excitation, were investigated in the vestibular nuclear complex following acute hypotension in adult Sprague-Dawley rats. Intravenous administration of nitroprusside elicited a 10-50% reduction in mean blood pressure for 10 min. Unilateral or bilateral chemical labyrinthectomies were performed 14 days before the start of the experiment to eliminate afferent signals from the peripheral vestibular receptors in the inner ear. All of the animals were sacrificed and the tissues were fixed 2 h after the onset of acute hypotension using the cardiac perfusion method for c-Fos immunohistochemical staining. The cFos-like immunoreactive (cFLI) neurons were expressed selectively in the central area of the medial vestibular nucleus following a 10% reduction in blood pressure. Once the blood pressure had fallen by 30%, bilateral expression of cFLI neurons was observed in the superior, medial, and spinal vestibular nuclei, but not in the lateral vestibular nucleus, of control rats with intact labyrinths. The expression of cFLI neurons increased proportionately with reductions in blood pressure. In unilaterally labyrinthectomized rats, acute hypotension induced the expression of cFLI neurons in vestibular nuclei contra lateral to the injured labyrinth, but not in the ipsilateral vestibular nuclei. However, cFLI neurons were not expressed in bilateral vestibular nuclei following acute hypotension in bilateral labyrinthectomized rats. These results suggest that afferent signals from the peripheral vestibular receptors are essential for cFos protein expression in the vestibular nuclei following acute hypotension.     

Rotational syndrome after central injection of C-terminal 7-peptide of cholecystokinin

Intracerebroventricular (ICV) injections of sulfated C-terminal 7-peptide of cholecystokinin and of its N-tert-butyloxycarbonyl-protected analog elicited rotational behavior (barrel rotations), accompanied by a distorted head and body position, lack of spontaneous motor activity other than rotations, characteristic limb flexion and extension and loss of some reflexes. When the unsulfated 7-peptide was ICV injected, none of the above symptoms was observed. The rotational syndrome described resembles the syndrome of acute unilateral labyrinthectomy. Since similar results have been reported following central injections of other peptides, however, it appears to be a non-specific, probably toxic effect.     

前庭损伤急性期清醒大鼠MVN区c-Fos蛋白的表达

目的:探讨破坏一侧前庭器官急性期清醒大鼠MVN区c-Fos蛋白表达的变化。方法:实验选用雄性Wistar系清洁级大鼠,分别在对照组和用对氨基苯砷酸盐破坏外周单侧前庭器官后6、12、24、48、72 h的动物,利用免疫组织化学法观察了MVN区c-Fos蛋白的表达情况。结果:①正常组和假破坏组动物MVN区c-Fos的表达不明显;②用对氨基苯胂酸盐破坏单侧外周前庭器官6 h、24 h、48 h、72 h时,破坏同侧MVN区仅有少量表达,但对侧则有明显的表达,尤其是48 h最为显著,而12 h时呈反向性表达,即损伤侧表达明显多于对侧。结论:清醒大鼠破坏前庭器官早期,MVN区c-Fos除12 h呈反向表达以外其他时间段,破坏对侧有明显表达,而同侧表达不明显。     

Protein kinase C inhibition blocks the early appearance of vestibular compensation

This study tests the hypothesis that activation of protein kinase C (PKC) is a critical step for early recovery from spontaneous nystagmus after unilateral ablation of the vestibular periphery. Halothane–NO₂–O₂-anesthetized Long–Evans rats received a 5-μl intracerebroventricular bolus of vehicle (distilled water, six rats), PKC inhibitor [Iso-H-7 (10 mM, four rats; 50 mM, five rats) or bisindolemaleimide I (Bis-I, 10 μM, six rats)], PKG and PKA inhibitor (A-3, 1 mM, six rats), or the serine–threonine protein kinase inhibitor H-7 (1 mM, five rats; 10 mM, five rats). Surgical unilateral labyrinthectomy (UL) was completed within 15 min. Sham control groups showed no nystagmus. Bis-I and Iso-H-7 significantly retarded the disappearance of spontaneous nystagmus quick phases for 8 h after UL (p<0.05). The effects of Iso-H-7 were dose-dependent: more nystagmus quick phases (p<0.05) were present in the 50 mM than the 10 mM group at 7 and 8 h post-UL. The rats given A-3 showed a delayed retardation of nystagmus loss, which differed significantly (p<0.05) from controls at 4–8 h after labyrinthectomy. The number of nystagmus quick phases was significantly greater than controls (p<0.05) in the 10 mM H-7 group at 4, 5, 6 and 48 h post-UL, but only at 6 and 24 h post-UL in the 1 mM H-7 group. Thus, PKC activation is an important early requirement for vestibular compensation during the acute post-labyrinthectomy period, while cyclic-nucleotide dependent kinases may be important in a later time frame.     

GABAergic inhibitory response of locus coeruleus neurons to caloric vestibular stimulation in rats

We examined the effects of caloric vestibular stimulation on the neuronal activity of the locus coeruleus (LC) in urethane-anesthetized rats. The middle ear cavity was irrigated with hot (44°C) or cold (30°C) water through a polyethylene tube. Most neurons (hot water: 76%, ; cold water: 90%, ) exhibited suppression of neuronal discharge in response to caloric stimulation. The suppression of LC neuronal discharge following caloric stimulation occurred with a long latency (approximately 80 s), and lasted a long period of time (approximately 3 min). Neither caloric stimulation of the auricle, nor irrigation of the middle ear with water at 37°C, nor caloric stimulation of the middle ear after labyrinthectomy inhibited LC neuronal discharge. The caloric stimulation-induced LC neuronal inhibition was significantly attenuated by the intravenous injection of picrotoxin and by the iontophoretic application of bicuculline methiodide. These findings indicate that the predominant effect of caloric vestibular stimulation on LC neuronal discharge is inhibitory, and that the caloric stimulation-induced LC neuronal inhibition is mediated by GABAA receptors located on the membrane of LC neurons. It is suggested that the suppressed activity of noradrenergic LC neurons is involved in the vestibulo-autonomic reflex.     

Changes in Fos Expression in the Rat Brainstem after Bilateral Labyrinthectomy

In order to elucidate the role of the vestibulocerebellar neural circuits during two-stage bilateral labyrinthectomy (BL) we examined Fos-like immunoreactive (-LIR) neurons as a marker of neural activation in the rat brainstem after BL and the projections of these neurons into the vestibulocerebellum using retrograde tracing and immunohistochemical techniques. Simultaneous BL did not show any Fos expression in the medial vestibular nucleus (MVe). However, with an interval of >6 h between the two stages of BL, Fos-LIR neurons were induced in the ipsilateral (ipsi-) MVe of the side operated on second, partially projecting into the ipsi-vestibulocerebellum. A previous study demonstrated that some of the unilateral labyrinthectomy-induced Fos-LIR neurons in the ipsi-MVe projected into the ipsi-vestibulocerebellum and inhibited the contra-MVe neurons, resulting in the restoration of the right-left balance. Taken together with our present data, it is suggested that some of the labyrinthectomy-induced Fos expression in the ipsi-MVe is representative of a switch-on signal for the vestibulo-cerebello-vestibular inhibitory neural circuits, which remain turned off after symmetrical lesions such as simultaneous BL but are turned on after severe asymmetrical lesions in order to restore the balance.     

Changes in calbindin expression within the flocculus after unilateral labyrinthectomy in rats

The role of flocculus in vestibular compensation is still a controversial issue. Calbindin regulates intracellular signaling and has been reported to be a reliable marker of Purkinje cell. Expression of calbindin in flocculus was examined using immunohistochemistry following unilateral labyrinthectomy (UL) in rats. Both the staining intensity and number of calbindin-positive Purkinje cells in the ipsilateral flocculus to the lesion side decreased 6 h after UL compared to the control and contralateral side. Forty-eight hours after UL, the expression of calbindin returned to control levels and asymmetric expression in bilateral flocculus subsided. These transient reduction of calbindin expression in the ipsilateral flocculus may reflect a decrease in the GABAergic inhibition of the floccular Purkinje cell to the ipsilateral vestibular nuclei during vestibular compensation.     

Fractionation of the cataleptic bracing response in rats

In haloperidol-treated rats, bracing, i.e., resistance to displacement along a horizontal surface, was found to involve four components: gripping by the digits, extension by the limbs, stiffening of the body axis and arching the vertebral column towards the displacing force. Labyrinthectomy weakened the bracing of the forequarters as did application of a head bandage. Labyrinthectomy, when combined with head bandage, completely abolished all forequarter bracing responses. Neither manipulation affected the bracing responses of the hindquarters. The hindquarter bracing reaction was abolished by application of an abdominal bandage, which left most of the forequarter responses intact. Isolation of fore- and hindquarter bracing responses revealed that whereas gripping by the digits and extension by the limbs could occur independently in either part of the body, stiffening of the body axis and arching of the vertebral column originated in the hindquarters. However, although these latter components of bracing originate in the hindquarters, as evidenced by their abolition with application of an abdominal bandage, their recruitment into the anterior of the body only occurred when the bracing of the forequarters was unimpaired. Either labyrinthectomy or head bandage prevented stiffening and arching of the vertebral column from occurring in the forequarters, even though these procedures had no effect on the hindquarters. Labyrinthectomy, head bandage and abdominal bandage all fractionated the bracing response over a wide range of haloperidol dosages (0.5, 1.0, 2,5, 5,0 and 7.5 mg/kg).