Vestibular compensation is an important model for developing the prevention and intervention strategies of vestibular disorders, and investigating the plasticity of the adult central nervous system induced by peripheral injury. Medial vestibular nucleus (MVN) in brainstem is critical center for vestibular compensation. Its neuronal excitability and sensitivity have been implicated in normal function of vestibular system. Previous studies mainly focused on the changes in neuronal excitability of the MVN in lesional side of the rat model of vestibular compensation following the unilateral labyrinthectomy (UL). However, the plasticity of sensitivity of bilateral MVN neurons dynamically responding to input stimuli is still largely unknown. In the present study, by using qPCR, whole-cell patch clamp recording in acute brain slices and behavioral techniques, we observed that 6 h after UL, rats showed a significant deficit in spontaneous locomotion, and a decrease in excitability of type B neurons in the ipsilesional rather than contralesional MVN. By contrast, type B neurons in the contralesional rather than ipsilesional MVN exhibited an increase in response sensitivity to the ramp and step input current stimuli. One week after UL, both the neuronal excitability of the ipsilesional MVN and the neuronal sensitivity of the contralesional MVN recovered to the baseline, accompanied by a compensation of spontaneous locomotion. In addition, the data showed that the small conductance Ca²⁺-activated K⁺ (SK) channel involved in the regulation of type B MVN neuronal sensitivity, showed a selective decrease in expression in the contralesional MVN 6 h after UL, and returned to normal level 1 week later. Pharmacological blockage of SK channel in contralateral MVN to inhibit the UL-induced functional plasticity of SK channel significantly delayed the compensation of vestibular motor dysfunction. These results suggest that the changes in plasticity of the ipsilesional MVN neuronal excitability, together with changes in the contralesional MVN neuronal sensitivity, may both contribute to the development of vestibular symptoms as well as vestibular compensation, and SK channel may be an essential ionic mechanism responsible for the dynamic changes of MVN neuronal sensitivity during vestibular compensation.
Animals ; Locomotion ; Neurons/physiology* ; Patch-Clamp Techniques ; Rats ; Vestibular Nuclei/metabolism* ; Vestibule, Labyrinth

OBJECTIVE: Studies revealed that cerebellar flocculus-paraflocculus complex plays an important in vestibular compensation. To observe the expression change of Group I mGluRs in flocculus following left unilateral labyrinthectomy (UL). METHOD: After setting left labyrinthectomy, the change of Group I mGluRs was detected by RT-PCR. RESULT: Group I mGluR5 was induced increase in both side flocculus after unilateral labyrinthectomy. By contrast, mGluR1 was induced decrease. However, that of the lesioned side was stronger than that of the unlesioned side. CONCLUSION UL can induce change of Group I mGluRs in the flocculus. The fall in the resting discharge of the primary vestibular afferents and/or in the deafferented central vestibular neurons may cause the change of mGluRs. But the significance of the change of mGluRs in the vestibular compensation is still unknown.
Animals ; Cerebellar Nuclei ; metabolism ; Male ; Rats ; Rats, Wistar ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate ; metabolism ; Vestibular Nuclei ; metabolism ; Vestibule, Labyrinth ; metabolism

To understand the neurochemical mechanisms underlying the vestibular compensation, we determined the levels of amino acids such as aspartate, glutamate, glutamine, glycine, taurine, alanine in the medial vestibular nucleus (MVN) following unilateral labyrinthectomy (UL), by using in vivo brain microdialysis and high-performance liquid chromatography technique. Rats were pretreated by infusing 2% lidocaine 1.2 mL or 10 mg arsanilic acid into the tympanic cavity to obstruct uni-periphery vestibular organ, and then the levels of amino acids were determined in MVN of normal control and ipsilateral or contralateral lesional (ipsi-/contra-lesional) rats. In the control experiment, the levels of aspartate, glutamate, glutamine, glycine, taurine, and alanine were (6.15 +/- 0.59), (18.13 +/- 1.21), (33.73 +/- 1.67), (9.26 +/- 0.65), (9.56 +/- 0.77) and (10.07 +/- 0.83) pmol/8 muL sample, respectively. The concentrations of aspartate and glutamate decreased, while the concentration of taurine increased in the ipsi-lesional MVN of rats 10 min after infusing 2% lidocaine into middle ear to obstruct uni-periphery vestibular organ. Whereas the concentration of glutamate increased, the concentrations of glycine and alanine decreased in the contra-lesional MVN, accompanied by imbalances of glutamate, glycine and alanine in the bilateral nuclei. In contrast, the levels of glutamate and alanine decreased, the level of glutamine increased in the ipsi-lesional MVN, and the level of glutamate decreased in the contra-lesional MVN of rats 2 weeks after infusing 10 mg arsanilic acid into the tympanic cavity to obstruct uni-periphery vestibular organ. Furthermore, the level of glutamine in the ipsi-lesional MVN was obviously higher than that in the contra-lesional MVN. These results demonstrate that an imbalance of different amino acids appeared in bilateral MVN after UL, and this imbalance decreased after the development of vestibular compensation. Whereas the imbalance of glutamine release in bilateral nuclei appeared after vestibular compensation.
Amino Acids ; metabolism ; Animals ; Aspartic Acid ; metabolism ; Ear, Inner ; physiology ; surgery ; Glutamic Acid ; metabolism ; Male ; Rats ; Rats, Wistar ; Taurine ; metabolism ; Vestibular Nuclei ; metabolism ; physiopathology

In order to understand whether some special amino acids in the medial vestibular nucleus (MVN) of rats are involved in the regulation of blood pressure, we used microdialysis technique and high performance liquid chromatography (HPLC) to measure the changes of glutamate and taurine in this central area. Acute hypotension was induced by hemorrhage from the femoral artery. It was observed that the basal release of glutamate and taurine in the MVN was stable about 90 min after the beginning of microdialysis. The basal release of glutamate was (18.96 +/- 0.27) pmol/sample (8 mul), and that of taurine was (7.73 +/- 0.05) pmol/sample (8 mul). Glutamate release increased (P<0.05) and taurine release reduced (P<0.05) in the MVN in the hemorrhage-induced acute hypotensive rats. Nevertheless, these changes were not observed in the hemorrhage-induced acute hypotensive rats which were pretreated by infusing 2% lidocaine into the middle ear or 100 mg arsanilic acid into the tympanic cavity. These results suggest that the hemorrhage-induced acute hypotention can influence the activity of the neurons in the MVN by the afferent impulses from vestibular organ, and that some special amino acid transmitters in the MVN are involved in this process.
Animals ; Blood Pressure ; physiology ; Glutamic Acid ; metabolism ; Hypotension ; metabolism ; physiopathology ; Male ; Microdialysis ; methods ; Rats ; Rats, Wistar ; Taurine ; metabolism ; Vestibular Nuclei ; metabolism ; physiopathology

OBJECTIVETo study the effect of nitric oxide (NO) in vestibular compensation after unilateral vestibular deafferentation.

METHODSEighteen animals were divided into two groups, 6 of group a as control, 12 of group b received gentamicin intratympanic injection in the left ear. Half of the animals were killed respectively after 5 days and 10 days. Vestibular endorgan and brainstem tissue sections were subjected to NADPH-d reactive test of NOS for histochemical examination.

RESULTSIn group a, NOS-like reactivity in both sides of vestibular endorgan and nucli. In group b during 5 days, NOS-like reactivity in right side of vestibular endorgan and nucli, those of the left side were negative. During 10 days, NOS-like reactivity only in the right side of vestibular endorgan.

CONCLUSIONSChanges of NOS expression in the contralateral vestibular nucli might have played a role in vestibular compensation.

Adaptation, Physiological ; Animals ; Brain Stem ; metabolism ; physiopathology ; Evoked Potentials, Auditory, Brain Stem ; Female ; Gentamicins ; Guinea Pigs ; Male ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Vestibular Nerve ; metabolism ; Vestibular Nuclei ; metabolism ; physiopathology ; Vestibule, Labyrinth ; injuries ; metabolism ; physiopathology

OBJECTIVE: To observe the expression of mGluR5 in the medial vestibular nucleus (MVN) following unilateral labyrinthectomy (UL). METHOD: Thirty Wistar rats were randomly divided into two groups. Twenty four animals received unilateral labyrinthectomy while the others maintained labyrinthine well. After setting left labyrinthine, the change of mGluR5 was induced by immunohistochemistry, in situ hybridization. RESULT: mGluR5 was increased in lesioned side MVN after unilateral labyrinthectomy. The 12 h post-UL was highest. Then it was decrease in 36 h post-UL, while 7 d post-UL was same as control group. The change of contralateral was same as that in ipsilateral. CONCLUSION UL can induce increase of mGluR5 in the MVN. The reduced resting discharge in the primary vestibular afferents or in the central vestibular neurons may be responsible for the change of mGluR5. However the significance of the change of mGluR1 in the vestibular compensation is still unknown.
Animals ; Male ; Postoperative Period ; Rats ; Rats, Wistar ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate ; metabolism ; Vestibular Nuclei ; metabolism ; Vestibule, Labyrinth ; metabolism ; surgery

OBJECTIVETo investigate modulation of gamma-aminobutyric acid (GABA) and its receptors on medial vestibular nucleus neurons in vivo.

METHODSTwenty-six male Wistar rats were used. gamma-aminobutyric acid, bicuculline (BIC, gamma-aminobutyric acid A receptor antagonist) and 2-hydroxysaclofen (SAC, gamma-aminobutyric acid B receptor antagonist) were microiontophoresed on medial vestibular nucleus (MVN) neurons to determine the effects of gamma-aminobutyric acid and its antagonists on the neuronal firing rates of medial vestibular nucleus in rats in vivo.

RESULTSMicroiontophoretic application of y-aminobutyric acid at 10, 30, 50 nA electric current produced inhibitory responses on 42 MVN neurons, these responses were dose-dependent decreases, firing rates (x +/- s) of MVN neurons decreased form (14.8 +/- 5.6) times/s to (8.7 +/- 3.4) times/s, (4.1 +/- 1.6) times/s and (2.2 +/- 1.1) times/s respectively; microiontophoretic application of bicuculline in 37 MVN neurons, 86.5% (32/37) neurons produced excitatory responses, 13.5% (5/37) neurons didn't response, firing rates of MVN neurons increased form (15.3 +/- 6.3) times/s to (16.8 +/- 7.1) times/s, (25.9 +/- 10.1) times/s and (32.7 +/- 11.3) times/s respectively at 10, 30, 50 nA electric current, which were dose-dependent increases, and the inhibitory responses of gamma-aminobutyric acid on MVN neurons were blocked by bicuculline completely; however, microiontophoretic application of 2-hydroxysaclofen didn't produced responses as bicuculline did.

CONCLUSIONSModulation of gamma-aminobutyric acid on medial vestibular nucleus neurons was mediated by y-aminobutyric acid A receptor in vivo.

Animals ; Electrophysiology ; Male ; Neurons ; drug effects ; physiology ; Rats ; Rats, Wistar ; Receptors, GABA ; metabolism ; Vestibular Nuclei ; cytology ; drug effects ; physiology ; gamma-Aminobutyric Acid ; pharmacology

To understand whether some amino acids in the medial vestibular nucleus (MVN) of conscious rats are involved in the regulation of blood pressure, microdialysis technique and high performance liquid chromatography (HPLC) were used to measure the changes of gamma-aminobutyric acid (GABA) and glycine (Gly) in this central area. Wistar rats (250-350 g) were randomly divided into three experimental groups: the control group with intact labyrinths; the ipsilateral MVN of unilateral labyrinthectomy (UL); contralateral MVN of the UL. Acute hypotension was induced by intravenous infusion of sodium nitroprusside (SNP). Unilateral chemical labyrinthectomy was performed 14 days before the start of the experiment to eliminate afferent signals from the peripheral vestibular receptors in the inner ear. Blood pressure decreased by 30% after SNP injection. In the control group, GABA and Gly release reduced to 43.53%+/-6.58% (P<0.01) and 62.24%+/-7.51% (P<0.01) respectively in the MVN following SNP-induced acute hypotension in conscious rats. In the contralateral MVN of UL, GABA and Gly release also reduced to 45.85%+/-17.27% (P<0.01) and 73.30%+/-3.00% (P<0.01) respectively following SNP-induced acute hypotension in conscious rats. In contrast, in the ipsilateral MVN of UL, GABA and Gly releases were not changed following SNP-induced acute hypotension in conscious rats. These results suggest that the SNP-induced acute hypotension may influence the activity of the neurons in the MVN by the afferent impulses from the peripheral vestibular organ, and that GABA and Gly may be involved in this process.
Acute Disease ; Animals ; Chromatography, High Pressure Liquid ; Ear, Inner ; physiology ; surgery ; Glycine ; metabolism ; Hypotension ; metabolism ; physiopathology ; Male ; Microdialysis ; Random Allocation ; Rats ; Rats, Wistar ; Vestibular Nuclei ; metabolism ; physiology ; gamma-Aminobutyric Acid ; metabolism