Research in Vestibular Science

Original Article

Application of Tetrode Technology for Analysis of Changes in Neural Excitability of Medial Vestibular Nucleus by Acute Arterial Hypotension: Young Kim, Ho Koo, Byung Rim Park, Se Jin Moon, Seung-Bum Yang, Min Sun Kim; Res Vestib Sci. 2018;17(4):142-151. Published online December 21, 2018; DOI: https://doi.org/10.21790/rvs.2018.17.4.142

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Abstract PDF: Objectives
Excitability o medial vestibular nucleus (MVN) in the brainstem can be affected by changes in the arterial blood pressure. Several animal studies have demonstrated that acute hypotension results in the alteration of multiunit activities and expression of cFos protein in the MVN. In the field of extracellular electrophysiological recording, tetrode technology and spike sorting algorithms can easily identify single unit activity from multiunit activities in the brain. However, detailed properties of electrophysiological changes in single unit of the MVN during acute hypotension have been unknown.
Methods
Therefore, we applied tetrode techniques and electrophysiological characterization methods to know the effect of acute hypotension on single unit activities of the MVN of rats.
Results
Twoor3typesofunitcouldbeclassifiedaccordingtothemorphologyofspikes and firing properties of neurons. Acute hypotension elicited 4 types of changes in spontaneous firing of single unit in the MVN. Most of these neurons showed excitatory responses for about within 1 minute after the induction of acute hypotension and then returned to the baseline activity 10 minutes after the injection of sodium nitroprusside. There was also gradual increase in spontaneous firing in some units. In contrast small proportion of units showed rapid reduction of firing rate just after acute hypotension. Conclusions: Therefore, application of tetrode technology and spike sorting algorithms is another method for the monitoring of electrical activity of vestibular nuclear during acute hypotension.

Review

Anatomy and Physiology of the Autonomic Nervous System: Byung Rim Park; Res Vestib Sci. 2017;16(4):101-107. Published online December 15, 2017; DOI: https://doi.org/10.21790/rvs.2017.16.4.101

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5 Crossref

The autonomic nervous system (ANS) integrates the function of the internal organs for the homeostasis against various external environmental changes. The efferent components of the ANS are regulated by sensory signals arising from the viscera as well as non-visceral organs. The central neural networks that integrate these sensory signals and modify visceral motor output are complex, and synaptic reflexes formed in the brainstem and spinal cord integrate behavioral responses and visceral responses through the central neural networks. A detailed understanding of the neural network presented above may explain the role of the vestibular system on the homeostasis more extensively.

Citations

Citations to this article as recorded by

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Anatomy and physiology of the autonomic nervous system: Byung Rim Park; Received November 14, 2017 Accepted November 25, 2017 Published online November 25, 2017; [Accepted]

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Abstract: 자율신경계는 다양한 외적 환경의 변화에 대하여 내적 환경을 일정하게 유지하는 항상성을 위하여 내장기관의 기능을 통합 조절한다. 자율신경계 조절의 원심성분인 교감신경과 부교감신경은 내장기관뿐만 아니라 비내장기관으로부터 발생한 구심성 감각신호에 의하여 조절된다. 이러한 감각신호를 통합하고 내장운동 출력을 변화시키는 중추신경회로망은 복잡하며, 뇌간과 척수에서 형성된 시냅스반사는 중추뇌신경회로를 통하여 행동반응과 내장반응을 통합하여 조절한다. 이상에서 제시한 신경회로망을 상세하게 이해한다면 전정기관이 항상성에 미치는 역할을 보다 광범위하게 설명할 수 있을 것이다.

Original Articles

Pathways of Neurogenic and Humoral Control in the Vestibulosympathetic Reflex of Conscious Rats: Guang Shi Jin, Gyoung Wan Lee, Sang Eon Park, Yuan Zhe Jin, Byung Rim Park; Res Vestib Sci. 2015;14(4):110-116.

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Abstract PDF: Objective: The vestibular system contributes control of blood pressure during postural changes through the vestibulosympathetic reflex. In the vestibulosympathetic reflex, afferent signals from the peripheral vestibular receptors are transmitted to the vestibular nuclei, rostral ventrolateral medullary nuclei, and then to the intermediolateral cell column of the thoracolumbar spinal cord. Physiological characteristics of the vestibulosympathetic reflex in terms of neurogenic and humoral control of blood pressure were investigated in this study.
Methods
Conscious rats with sinoaortic denervation were used for removal of baroreceptors in reflex control of blood pressure, and hypotension was induced by intravenous infusion of sodium nitroprusside (SNP). Expression of c-Fos protein was measured in the medial vestibular nuclei (MVN), rostral vestrolateral medullary nuclei (RVLM), and intermediolateral cell column (IMC) in T4-7, and levels of blood epinephrine were measured following SNP-induced hypotension.
Results
SNP-induced hypotension significantly increased expression of c-Fos protein in the MVN, RVLM, and IMC, also significantly increased level of blood epinephrine compared to normotensive control animals.
Conclusion
These results suggest that the vestibulosympathetic reflex regulates blood pressure through neurogenic control including MVN, RVLM, and IMC, also through humoral control including epinephrine secretion by the adrenal medulla following SNP-induced hypotension. The physiological characteristics of the reflex may contribute to basic treatment of impairment of blood pressure control during postural changes.

Role of the Cerebral Cortex on Vestibular Compensation Following Unilateral Labyrinthectomy in Rats: Hyun Kwang Ryoo, Seung Bum Yang, Min Sun Kim, Byung Rim Park; Res Vestib Sci. 2015;14(3):75-82.

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Abstract PDF: Objective: The cerebral cortex can modulate vestibular functions through direct control of neuronal activities in the vestibular nuclei. The purpose of this study was to investigate the effect of unilateral cortical lesion or cortical stimulation on static vestibular symptoms and vestibular nuclear activities at the acute stage of vestibular compensation following unilateral labyrinthectomy (UL) in rats.
Methods
The photothrombic ischemic injury using rose bengal was induced in the primary motor cortex or primary sensory cortex, and electrical stimulation was applied to the primary motor cortex, primary sensory cortex, or sencondary sensory cortex, respectively, in unilateral labyrinthectomized rats. Static vestibular symptoms including ocular movement and postural deficits, and expression of c-Fos protein in the medial vestibular nucleus (MVN) were measured.
Results
Lesion of the motor cortex produced a marked postural deficit with paralytic weakness in the hindlimb contralateral to UL. Number of spontaneous nystagmus in animals receiving cortical lesion was significantly increased 2, 6, and 12 hours after UL compared with animals being UL only. Lesion of the primary motor cortex or stimulation of the S2 sensory cortex decreased expression of c-Fos protein in MVN following UL compared with UL only group. Electrical stimulation of S2 sensory areas caused significant reduction of static vestibular symptoms and decreased expression of c-Fos protein in MVN 24 hours following UL.
Conclusion
The present results suggest that cerebral cortex involves in recovery of static vestibular symptoms during vestibular compensation following UL.

Expression of Metabotropic Glutamate Receptors in the Medial Vestibular Nucleus Following Acute Hypotension in Rats: Myoung Ae Choi, Nari Kim, Sang Eon Park, Byung Geon Park, Min Sun Kim, Byung Rim Park; Res Vestib Sci. 2012;11(4):131-137.

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Abstract: Background and Objectives: Acute hypotension induces expression of c-Fos protein and phosphorylated extracellular signal-regulated kinase (pERK), and glutamate release in the vestibular nuclei. Expression of c-Fos protein and pERK is mediated by the excitatory neurotransmitter, glutamate. In this study, the signaling pathway of glutamate in the vestibular nuclei following acute hypotension was investigated. Materials and Methods: Expression of metabotropic glutamate receptors (mGluRs) was measured by Western blotting in the medial vestibular nucleus following acute hypotension in rats. Results: Expression of pGluR1 Ser831, a subtype of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, peaked at 30 minutes after acute hypotension insult, and expression of pNR2B, a subtype of N-methyl-D-aspartate (NMDA) receptors, peaked at 2 hours after acute hypotension insult. Acute hypotension induced expression of Homer1a and group I mGluR in the medial vestibular nucleus. Expression of mGluR1 and mGluR5 peaked at 6 hours following acute hypotension insults. Conclusion: These results suggest that afferent signals from the peripheral vestibular receptors, resulting from acute hypotension insult, are transmitted through group I mGluRs as well as AMPA and NMDA receptors in the vestibular system.

Role of the Peripheral Vestibular End Organ in the Expression of c-Fos Protein in the Medial Vestibular Nucleus Following Occlusion of the Anterior Inferior Cerebellar Artery: Nari Kim, Jae Hee Lee, Myoung Ae Choi, Byung Geon Park, Min Sun Kim, Byung Rim Park; Res Vestib Sci. 2012;11(2):51-58.

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Abstract PDF: Background and Objectives: The present study investigated the role of the peripheral vestibular end organ in vestibular symptoms and temporal changes in expression of c-Fos protein in the vestibular nuclei following anterior inferior cerebellar artery (AICA) occlusion using rats with unilateral or bilateral labyrinthectomy. Materials and Methods: Expression of c-Fos protein in the vestibular nuclei was measured 2, 12, 24, and 48 hours after AICA occlusion. Results: Unilateral AICA occlusion significantly induced expression of c-Fos protein bilaterally in the medial, inferior, superior, and lateral vestibular nuclei. Following AICA occlusion, the medial vestibular nucleus (MVN) showed the highest expression of c-Fos protein among the 4 vestibular nuclei. The expression of c-Fos protein was asymmetric between the bilateral MVN, showing higher expression in the MVN contralateral to the side of AICA occlusion compared to the ipsilateral MVN. The degree of asymmetry in c-Fos protein expression between the bilateral MVN peaked 12 hours after AICA occlusion. The expression of c-Fos protein gradually decreased 24 hours after AICA occlusion and returned to control levels 48 hours after AICA occlusion. Unilateral labyrinthectomy significantly decreased expression of c-Fos protein in the MVN ipsilateral to the side of labyrinthectomy following AICA occlusion. Moreover, bilateral labyrinthectomy significantly decreased expression of c-Fos protein in the bilateral MVN flowing AICA occlusion. Conclusion: These results suggest that afferent signals from the peripheral vestibular end organ are crucial to the expression of c-Fos protein in the MVN following AICA occlusion and that expression of c-Fos protein is sustained for 24 hours after AICA occlusion.

Application of Force Sensitive Resistors on Evaluation of Vestibulospinal Reflex Induced by Galvanic Stimulation: Sang Eon Park, Jin Hee Park, Min Sun Kim, Ho Choon Jeong, Byung Rim Park; Res Vestib Sci. 2011;10(3):92-99.

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Abstract PDF: Background and Objectives: Force sensitive resistors (FSR) were used to measure the body sway to galvanic vestibular stimulation (GVS), and compared with the response obtained from force platform in normal subjects. Materials and Methods: Bipolar galvanic stimulation was applied to the bilateral mastoid process with intensity of 0.5-1.5 mA and duration of 1 sec in 3 different head positions of forward, rightward, and leftward. Results: Elevation of anterior pressure curve and depression of posterior pressure curve resulting from forward body sway were recorded in both feet by FSR. Forward body sway induced forward deviation of the center of pressure in force platform. Elevation of pressure curve in left foot and depression of the curve in right foot resulting from leftward body sway were recorded by FSR. Leftward body sway induced left deviation of the center of pressure in force platform. Orientation of the body sway induced by GVS was directed towards the anode side in the head facing forwards. Leftward and backward body sway resulting from cathodal stimulation on left mastoid process in leftward rotation of the head position and leftward and forward body sway resulting from cathodal stimulation on left mastoid process in rightward rotation of the head position were recorded by both FSR and force platform. Reaction time of GVS did not show any significant difference between FSR and force platform. Conclusion: These results indicate that FSR could be used to evaluate the vestibulospinal reflex to GVS.

Review

Understanding of Structure and Function of Vestibular Cortex: Min Sun Kim, Jae Hee Lee, Gyoung Wan Lee, Byung Rim Park; Res Vestib Sci. 2010;9(1):1-11.

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Abstract PDF: The vestibular end-organs generate very sophisticated gravity sensory information about head movement by sensing head acceleration in three-dimensional space. Vestibular information is crucial for higher brain functions such as cognition of spatial orientation, spatial memory, and perception of self-motion. The term “vestibular cortex” represents cortical area where vestibular information is processed, converged with other sensory inputs to maintain cortical functions. The vestibular cortex gives rise to commend signals that control the vestibulosomatic reflex through the modulation of vestibular nuclear activity in the brainstem. The vestibular cortex includes such different cortical regions as the premotor region of the frontal cortex, parietal areas, temporal areas, and a central core region called parietoinsular vestibular cortex. This paper summarizes systemically animal and clinical research data concerned with the vestibular cortex in order to understand anatomy and functions of the vestibular cortex and to provide a basic literature for further study.

Original Article

Expression of Glutamate Receptors in the Medial Vestibular Nuclei following Acute Hypotension: Jae Hee Lee, Myoung Ae Choi, Dong Ok Choi, Bo Kyoung Kim, Seok Min Hong, Byung Rim Park; J Korean Bal Soc. 2007;6(1):29-35.

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Abstract PDF: Acute hypotension induced excitation of electrical activities and expression of c-Fos protein and pERK in the vestibular nuclei. In this study, to investigate the excitatory signaling pathway in the vestibular nuclei following acute hypotension, expression of NR2A and NR2B subunits of glutamate NMDA receptor and GluR1 subunit of glutamate AMPA receptor was determined by RT-PCR and Western blotting in the medial vestibular nucleus 30 min after acute hypotension in rats. Acute hypotension increased expression of NR2A, NR2B, and pGluR1 in the medial vestibular nuclei. These results suggest that both of NMDA and AMPA glutamate receptors take part in transmission of excitatory afferent signals following acute hypotension.

Case Reports

Unilateral Peripheral Vestibulopathy associated with Cerebral Venous Infarction: Hyun Ah Kim, Hyung Lee, Byung Rim Park; J Korean Bal Soc. 2006;5(2):285-287.

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Abstract PDF: Cerebral venous infarction is associated with a wide variety of clinical symptoms and signs, which may often delay appropriate diagnosis. Unilateral vestibular deficit as a presenting sign of cerebral venous infarction has rarely been reported. We report a patient with cerebral venous infarction who had severe prolonged vertigo, vomiting, occipital headache, positive head thrust testing, and unilateral caloric weakness as main clinical features. Although the patient had occipital headache, overall symptoms and signs closely mimicked those of acute peripheral vestibulopathy. Key Words : Peripheral vestibulopathy, Brain infarction

Vestibular Neuritis of Vascular Cause: Hyun Ah Kim, Hyung Lee, Byung Rim Park; J Korean Bal Soc. 2006;5(2):277-280.

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Abstract PDF: Vestibular neuritis (VN) is an idiopathic peripheral vestibular syndrome characterized by acute isolated prolonged vertigo. In most cases, it results from inflammation of the vestibular nerve presumably of viral origin. There has been no previous report of VN associated with a vascular cause. We here report a patient with VN of vascular origin who presented with acute onset of prolonged isolated vertigo, a unilateral decreased caloric response, and simultaneously with acute infarcts on brain MRI that were unrelated to patient's vertigo. Key Words : Vestibular neuritis, Cerebral infarction

Original Articles

Body Lateropulsion as an Isolated or Predominant Symptom of a Pontine Infarction: Hyun Ah Kim, Hyung Lee, Byung Rim Park; J Korean Bal Soc. 2006;5(2):224-228.

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Abstract PDF: Background
and Objectives: Body lateropulsion with falling to one side is a well-known clinical feature of stroke in the posterior circulation. Body lateropulsion as an isolated or predominant manifestation of a pontine stroke has not previously been reported. To elucidate the possible mechanisms of patients presenting with body lateropulsion as an isolated or predominant symptom of isolated pontine infarction. Materials and Method: Between May 2004 and February 2006, out of 134 admitted patients with an isolated pontine stroke we identified 8 consecutive patients (6.0%) in the Keimyung University Stroke Registry who had body lateropulsion as the main presenting symptom.
Results
All lesions were localized to the paramedian tegmentum just ventral to the 4th ventricle. All except 1showed a uniform pattern of body lateropulsion, in which the direction of falling was away from the side of infarct. In 2 patients, body lateropulsion was the sole clinical manifestation, whereas the other patients had other neurological signs. All but 1 had contraversive tilting of the subjective visual vertical (SVV). In all cases, the direction of SVV tilt corresponded to the direction of body lateropulsion. The mean net tilt angle was 6.1
Conclusion
Based on the known anatomy of ascending vestibular pathways, the SVV tilting, and MRI findings, body lateropulsion probably results from damage to the graviceptive pathway ascending through paramedian pontine tegmentum. Key Words : Pons, Infarction

Role of the Peripheral Vestibular System on Neuroplasticity Induced by Hypergravity Stimulation: Jae Hyo Lee, Gyoung Wan Lee, Han Su Park, Jae Hee Lee, Dong Ok Choi, Myoung Ae Choi, Byung Rim Park; J Korean Bal Soc. 2006;5(2):213-223.

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Abstract PDF: Background
and Objectives: Altered environmental gravity, including both hypo- and hypergravity, may result in space adaptation syndrome. To explore the characteristics of this adaptive plasticity, the expression of immediate early gene c-fos mRNA in the vestibular system following an exposure to hypergravity stimulus was determined in rats. Materials and Method: The animals were subjected to 2 G force (two-fold earth's gravity) stimulus for 3 hours, and were examined at post-stimulus hours 0, 2, 6, 12, and 24. Real time reverse transcription-polymerase chain reaction (RT-PCR) was adopted to analyze temporal changes in the expression of c-fos mRNA.
Results
The hypergravity stimulation produced the expression of c-fos mRNA in the vestibular ganglion, medial vestibular nucleus, inferior vestibular nucleus, hippocampus, vestibulocerebellum, and vestibular cortex. The peak expression occurred at hour 6 in the animals hypergravity-stimulated for 3 hours. Bilateral labyrinthectomy significantly attenuated the degree of up-regulation in c-fos mRNA expression. MK-801, an NMDA receptor antagonist, also significantly attenuated the degree of up-regulation in c-fos mRNA expression.
Conclusion
These results indicate that the adaptive neuroplasticity in response to an altered gravity occurs in the vestibular-related organs in the central nervous system, in which peripheral vestibular receptors and NMDA receptors play an important role. Key Words : Hypergravity, Neuronal plasticity, Vestibule, c-fos gene

Expression of Caveolin-1 in the Differentiated Vestibular Cell Line (UB/UE-1) after Gentamicin Toxicity: Byung Han Cho, Kyu Sung Kim, Min Wook Kim, Min Sun Kim, Byung Rim Park; J Korean Bal Soc. 2005;4(2):243-249.

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Abstract PDF: Background
and Objectives: The caveolin is known as a mediator of cell death or survival of injured cell and inhibitor of various signaling pathways. We examined expression of caveolin-1 involved by protein kinase A(PKA) signaling pathway in the differentiated mouse vestibular cell line(UB/UE-1) after gentamicin toxicity. Materials and Method: We observed caveolae in the vestibular hair cell of healthy guinea pig through electron microscope. UB/UE-1 cells were cultured at 95% CO2, 5% O2, 33℃ for 2days and at 95% CO2, 5% O2, 39℃ for 24 hours for differentiation. Cells were treated with 1 mM of gentamicin, 0.02 mM H89 (PKA inhibitor), and then incubated for 24 hours. Caveolin-1 expression was examined by western blot and PKA activity by PepTagⓇ assay.
Results
Caveolae were observed in the vestibular hair cell of healthy guinea pig by electron microscope. Caveolin-1 was expressed spontaneously in differentiated UB/UE-1 cells and increased after gentamicin treatment. PKA is overactivated by gentamicin treatment. The gentamicin induced caveolin-1 expression and PKA overactivation was inhibited by H89.
Conclusion
Our results indicate that gentamicin induced caveolin-1 expression is mediated by PKA signaling pathway. We conclude that the caveolae/caveolin through a PKA signaling pathway is the important mechanism of gentamicin induced ototoxicity.

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