Reduction of long-term potentiation at Schaffer collateral-CA1 synapses in the rat hippocampus at the acute stage of vestibular compensation

Vestibular compensation is a recovery process from vestibular symptoms over time after unilateral loss of peripheral vestibular end organs. The aim of the present study was to observe time-dependent changes in long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in the CA1 area of the hippocampus during vestibular compensation. The input-output (I/O) relationships of fEPSP amplitudes and LTP induced by theta burst stimulation to Schaffer's collateral commissural fibers were evaluated from the CA1 area of hippocampal slices at 1 day, 1 week, and 1 month after unilateral labyrinthectomy (UL). The I/O relationships of fEPSPs in the CA1 area was significantly reduced within 1 week post-op and then showed a non-significant reduction at 1 month after UL. Compared with sham-operated animals, there was a significant reduction of LTP induction in the hippocampus at 1 day and 1 week after UL. However, LTP induction levels in the CA1 area of the hippocampus also returned to those of sham-operated animals 1 month following UL. These data suggest that unilateral injury of the peripheral vestibular end organs results in a transient deficit in synaptic plasticity in the CA1 hippocampal area at acute stages of vestibular compensation.

Changes in the Gastrointestinal Motility following Unilateral Labyrinthectomy / 대한평형의학회지

BACKGROUND AND OBJECTIVES The temporal changes and the role of glutamate receptors in the recovery of vestibulogastrointestinal symptoms following unilateral labyrinthectomy (UL) were investigated in this study. Vestibulogastrointestinal symptoms were evaluated in terms of gastric emptying and intestinal transit. MATERIALS AND METHODS Expression of the c-Fos protein was observed in the solitary tract nucleus (STN) and rostral ventrolateral medullary nucleus (RVLM). These were measured at 0.5, 2, 6 and 24 h following UL in rats. RESULTS Gastric emptying and intestinal transit were significantly decreased for 6 h post UL and recovered to control levels within 24 h. Pretreatment of UL animals with MK-801 significantly increased the gastric emptying and intestinal transit. Bilateral labyrinthectomy significantly decreased the gastric emptying and intestinal transit compared to the intact labyrinthine animals but significantly increased when compared to UL animals. The expression of c-Fos protein was significantly increased in STN and RVLM compared to the control animals for 6 h post UL and recovered to control levels within 24 h. The expression was significantly decreased in animals that were pretreated with MK-801. CONCLUSION These results suggest that UL decreases the gastrointestinal motility, which recovers to control levels within 24 h post UL. Glutamate plays an important role in the recovery of vestibulogastrointestinal symptoms following UL.

Activation of cAMP-Response Element Binding Protein in the Brain Stem Nuclei during Vestibular Compensation in Unilateral Labyrinthectomizied Rats / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The p-CREB (phospholyated form of cAMP/calcium response element binding protein) was known to be one of transcription factors for immediate early genes in the brain stem nuclei. The purpose of this present study was to evaluate time-dependent expression of p-CREB and investigate the effect of MK801, non-competitive NMDA channel blocker, on p-CREB expression following unilateral labyrinthectomy (ULX). MATERIALS AND METHODS: Adult Sprague-Dalwey rats weighing 250-300 g were divided into a control group and an unilateral labyrinthetomy (ULX) group. The intraperitoneal injection of MK801 was administered either 30 min before or 24 hrs after ULX. The ABC immunohistochemical staining and digital image analysis system were used to measure the p-CREB expression in neuronal cells. RESULTS: The peak level of p-CREB expressions in 4 major vestibular nuclei was observed bilaterally with the other brain stem nuclei including reticular formation and olivary complex at 30 min following ULX. Thereafter, the p-CREB immunoreactivity in these nuclei was reduced rapidly to the control level for 6 hrs after ULX. Treatment of MK801 for 30 min preceding ULX decreased p-CREB immunoreactivity significantly in both the injured and intact sides of the 4 major vestibular nuclei with dose-dependent relationship. However, MK801 did not affect the change of p-CREB immunoreactivity in bilateral vestibular complex 24 hrs after ULX. CONCLUSION: These results suggest that cAMP/calcium response element binding protein plays an important role in the initial events of vestibular compensation in which its activity is in part regulated by NMDA receptor.

The Role of the Cerebellar Uvulonodulus on the Early Stage of Vestibular Compensation in Rats / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Many expeerimental evidences have beensupported that the vestibulocerebellum involved in recovery of vestibular compensation. The purpose of this study was to investigate effect of unilateral ablation of uvula and nodular lobes on early stage of vestibular compensation. MATERIALS AND METHODS: Adult Sprague-Dawley rats weighing 250~300 g were used and divided into control (CON) group receiving sham operation, unilateral labyrinthectomy (ULX) group, ULX plus left uvulonodulectomy (ULX+Lt-UNLX) group, and ULX plus right uvulonodulectomy (ULX+Rt-UNLX) group. UNLX was performed 1 hour following ULX. Spontaneous nystagmus (SN) and roll head tilt (RHT) were recorded for 3 days following ULX. Temporal change of c-Fos protein expression in the medial vestibular nuclei (MVN) was measured for 2 days following ULX. RESULTS: There were observed SN with contralateral direction to injured labyrinth and RHT toward ipsilateral side with flexion of ipsilateral limb and extenstion of contralateral one just after ULX. There was significant increase in SN frequency of ULX+Rt-UNLX group compared with that of ULX group. In addition, ULX+Rt-UNLX group resulted in severe postural asymmetry. ULX elicited prominent expression of c-Fos protein in contralateral MVN 2 hours but in ipsilateral one 6, 24 hours after ULX, respectively. In contrast, number of c-Fos positive neurons was higher in contralateral MVN. 24 hours after ULX higher expression of c-Fos protein in contralteral MVN was still remained in ULX+Rt-UNLX group but that in ipsilateral MVN was observed in ULX+Lt-UNLX group. CONCLUSION: These results suggest that UNLX have a different effect on the early stage of vestibular compensatory process and the uvulonodulus serves the restoration of balance between intervestibular nuclear activities after ULX by inhibition of vestibular nuclear complex through nhibitory Purkinje system.

Temporal changes in neuronal activity of the bilateral medial vestibular nuclei following unilateral labyrinthectomy in rats

To investigate the changes in the responses of vestibular neurons with time during vestibular compensation, the resting activity and dynamic responses of type I and II neurons in the medial vestibular nuclei to sinusoidal angular acceleration were recorded following unilateral labyrinthectomy (ULX) in Sprague-Dawley rats. The unitary extracellular neuronal activity was recorded from the bilateral medial vestibular nuclei with stainless steel microelectrodes of 3~5 MOMEGA before ULX, and 6, 24, 48, 72 hours, and I week after ULX under pentobarbital sodium anesthesia (30 mg/kg, i.p.). Gain (spikes/s/deg/s) and phase (in degrees) were determined from the neuronal activity induced by sinusoidal head rotation with 0.05, 0.1, 0.2, and 0.4 Hz. The mean resting activity before ULX was 16.7+/-8.6 spikes/s in type I neurons (n=67, M+-SD) and 14.5+/-8.4 spikes/s in type II neurons (n=43). The activities of ipsilateral type I and contralateral type 11 neurons to the lesion side decreased markedly till 24 hr post-op, and a significant difference between ipsilateral and contralateral type I neurons sustained till 24 hr post-op. The gain at 4 different frequencies of sinusoidal rotation was depressed in all neurons till 6 or 24 hr post-op and then increased with time. The rate of decrease in gain was more prominent in ipsilateral type I and contralateral type 11 neurons immediately after ULX. Although the gain of those neurons increased gradually after 24 hours, it remained below normal levels. The phase was significantly advanced in all neurons following ULX. These results suggest that a depression of activities in ipsilateral type I and contralateral type II neurons is closely related with the occurrence of vestibular symptoms and restoration of activities in those neurons ameliorates the vestibular symptoms.

Effects of MK801 on Neuronal Activity of the Contralateral Medial Vestibular Nuclei Following Unilateral Labyrinthectomy in Rats / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Several lines of evidence suggest that recovery of symptoms following unilateral labyrinthectomy (ULX) is due to the restoration of neuronal activity in the ipsilateral vestibular nuclei, leading to the reestablishment of bilateral symmetry in the resting neuronal activity. Effects of dizocilpine maleate (MK801), a non-competitive NMDA receptor antagonist, on vestibular compensation following unilateral labyrinthectomy (ULX) were investigated in adult Sprague-Dawley rats. MAERIAL AND METHODS: Responses of spontaneous nystagmus and neuronal activity of the contralateral medial vestibular nuclei (MVN) to labyrinthectomy were recorded in course of time after intraperitoneal injection of MK801. RESULT: Spontaneous nystagmus decreased gradually with time, but recovery of the nystagmus was aggravated 2 to 4 hours after administration of MK801 (p<0.05). In the labyrinthine intact rats, MK801 treatment significantly increased resting activity of type I and II in MVN compared with non-treated rats, and the effect of MK801 on neuronal activity was more prominent in the type I neurons than in the type II neurons. After 6 hours of ULX, the activities of type I and II neurons were decreased compared with labyrinthine intact rats, and type II neurons showed higher activity than the type I neurons. MK801 treated ULX rats showed higher resting activity in the type I and II neurons than in the labyrinthine intact rats or ULX rats, but lower resting activity than the MK801 treated labyrinthine intact rats. In the neuronal activity induced by sinusoidal rotation, gain was the highest in the MK801 treated ULX rats among the 4 experimental groups, and sensitivity was decreased in the type I & II neurons by treatment of MK801. CONCLUSION: These results suggest that MK801 deteriorates asymmetry of the resting activity in the bilateral MVN by inhibition of cerebellar Purkinje system inhibiting the intact MVN, which results in decompensation of the vestibular function following ULX.

Spontaneous, Positional, Positioning and Post Head Shaking Nystagmus in Unilaterally Labyrinthectomized Cats / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Unilateral vestibular dysfunction evokes many bothersome symptoms such as nausea, vomiting, vertigo, ataxia, and positional change. We attempted to understand the vestibular signs after a loss of unilateral vestibular function. MATERIALS & METHOD: We evaluated the serial changes of eye movements and body posture after unilateral labyrinthectomy which was performed on five cats. Data obtained from three of these cats. The eye movements were measured in vertical, horizontal and torsional planes using magnetic search coils, with eyes open in light and eyes open in darkness. The eye movements were recorded with head in neutral, tilted, hanging, and Dix-Hallpike position, and after head was shaken. RESULTS: 1) Spontaneous nystagmus was present for the first three days. 2) Head tilting positional nystagmus was present only on the first day after the operation. Head hanging position produced nystagmus with high slow phase eye velocity for 4 weeks. 3) Positioning nystagmus was recorded for 4 weeks and it was more prominent when labyrinthectomized ear was undermost. 4) Head shaking nystagmus around the pitch and roll axis was evoked within one week, but in the yaw axis it persisted for 4 weeks. When the cat was tilted to the lesion side, the intensitiy of positional and positioning nystagmus was stronger. CONCLUSION: Unusual positions such as head hanging and Dix-Hallpike position evoked prolonged nystagmus. Head shaking in the yaw axis could be used on a long term basis to understand unilateral vestibular dysfunction.

c-fos Expression in Medial Vestibular Nucleus of Guinea Pigs After Unilateral Labyrinthectomy / 听力学及言语疾病杂志

Objective To investigate the c-fos ex pr ession in guinea pigs' medial vestibular neuleus (MVN) following unilateral laby rinthectomy (UL). Methods Twenty-seven SCO guinea pigs were randomly divide d into nine groups, three in each group. After resection of right labyrinth,th e immunohistological staining of c-fos was performed. Fos-like immunoreactivity (FLI) was analyzed at fifteen minutes, and 1?2?6?8?12 and 24 h, and 2 and 7 days after UL. Results Results showed no Fos expression in the control g roup. By contrast, Fos was consistently induced in the UL guinea pigs. Asymmetri cal labeling was found in the bilateral medial vestibular nucleus, with more Fos -like neurons in the ipsilateral MVN of the lesioned side than that in the contr alateral MVN(P

Effects of electrical stimulation of the vestibular system on neuronal activity of the ipsilateral medial vestibular nuclei following unilateral labyrinthectomy in rats

The purpose of this study was to evaluate the effects of electrical stimulation on vestibular compensation following ULX in rats. Electrical stimulation (ES) with square pulse (100 ~ 300 uA, 1.0 ms, 100 Hz) was applied to ampullary portion bilaterally for 6 and 24 hours in rats receiving ULX. After ES, animals that showed the recovery of vestibular symptoms by counting and comparing the number of spontaneous nystagmus were selected for recording resting activity of type I, II neurons in the medial vestibular nuclei (MVN) of the lesioned side. And then the dynamic neuronal activities were recorded during sinusoidal rotation at a frequency of 0.1 Hz and 0.2 Hz. The number of spontaneous nystagmus was significantly different 24 hours (p< 0.01, n = 10), but not 6 hours after ULX+ES. As reported by others, the great reduction of resting activity only in the type I neurons ipsilateral to lesioned side was observed 6, 24 hours after ULX compared to that of intact labyrinthine animal. However, the significant elevation (p < 0.01) of type I and reduction (p < 0.01) of type II neuronal activity were seen 24 hours after ULX+ES. Interestingly, gain, expressed as maximum neuronal activity(spikes/sec)/maximum rotational velocity (deg/sec), was increased in type I cells and decreased in type II cells 24 hours after ULX+ES in response to sinusoidal rotation at frequencies of both 0.1 Hz and 0.2 Hz. This result suggests that accompanying the behavioral recovery, the electrical stimulation after ULX has beneficial effects on vestibular compensation, especially static symptoms (spontaneous nystagmus), by enhancing resting activity of type I neurons and reducing that of type II neurons.

Correlation between electrical activity of type I neuron and c-Fos expression in the medial vestibular nuclei following unilateral labyrinthectomy in rats

To search the correlations between electrical activity and c-Fos expression in the process of vestibular compensation, we examined the changes of those two parameters in the medial vestibular nuclei (MVN) of unilaterally labyrinthectomized (ULX) rats. Spontaneous nystagmus with fast component toward the intact side disappeared gradually within 48 hours. Fourty eight hours after ULX, directional preponderance of the eye movement induced by sinusoidal rotation of the whole body which represents the symmetry of bilateral vestibular functions showed less than 20% by rotation of 0.1, 0.2, and 0.5 Hz, indicating the recovery of symmetry in bilateral vestibular functions. Six hours after ULX, spontaneous electrical activity of type I neurons resulted in asymmetry between bilateral MVN, however, the asymmetry of the electrical activity was decreased 48 hours after ULX. Immunocytochemical staining revealed that ULX produced dramatic induction of c-Fos positive cells in the MVN bilaterally. The number of c-Fos immunoreactive cells in the contralateral MVN was significantly higher than those in the ipsilateral MVN (p<0.0001) 2 hours after ULX. Thereafter, the number of c-Fos positive cells decreased bilaterally and was slightly, but not significantly higher in the ipsilateral MVN at 48 hours after ULX. The present results suggest that both electrical activity of type I neurons and c-Fos expression in MVN following ULX will reflect underlying mechanisms of recovery process of vestibular compensation.

Relationship between Recovery of Vestibuloocular Reflex and c-Fos Protein Expression in Medial Vestibular Nuclei Following Unilateral Labyrinthectomy in Rats / 대한이비인후과학회지

Relationships between recovery of vestibuloocular reflex and expression of c-fos immunoreactive cells in the medial vestibular nuclei following unilateral labyrinthectomy(ULX) were investigated in rats. Frequency of spontaneous nystagmus, velocity of eye movement induced by sinusoidal rotation of the whole body at frequencies of 0.1, 0.2, 0.5Hz, and the number of c-fos immunoreactive cells in the medial vestibular nuclei were measured for 72 hours after ULX. Frequency of spontaneous nystagmus was 3.9+/-0.5 beats/sec(M+/-SD) immediately after ULX and disappeared completely within 48 hours. On sinusoidal rotation, eye movement induced by rotation toward the lesioned side recovered normal pattern within 24 hours at 0.1Hz rotation, and 12 hours at 0.2, 0.5Hz. Directional preponderance which represents the symmetry of bilateral vestibular functions decreased to less than 20% at 72 hours, but did not recover normal limit. The number of c-fos immunoreactive cells in the bilateral medial vestibular nuclei was severe asymmetry till 24 hours of ULX. However, the symmetry was recovered after 48 hours. These results indicate that the recovery of vestibuloocular reflex correlates with the expression of c-Fos immunoreactive cells of the medial vestibular nuclei in the early stage of vestibular compensation following ULX. Therefore, the vestibular nuclei may play a key role in vestibular compensation.