Activation of the thalamic parafascicular nucleus by electrical stimulation of the peripheral vestibular nerve in rats.

The parafascicular nucleus (PFN) of the thalamus is a primary structure in the feedback circuit of the basal ganglia-thalamo-cortical system, as well as in the neural circuit of the vestibulo-thalamo-striatal pathway. We investigated the characteristics of the functional connectivity between the peripheral vestibular system and the PFN in rats. A single electrical stimulation was applied to the horizontal semicircular canal nerve in the peripheral vestibular end-organs. This resulted in polysynaptic local field potentials (LFPs) in the PFN, which were composed of long-lasting multiple waves. The LFPs were prominently seen contralateral to the stimulation site. The PFN LFPs were suppressed by transient chemical de-afferentation of peripheral vestibular activity using a 5% lidocaine injection into the middle ear. The spontaneous firing rate of the single units increased after electrical stimulation to the horizontal canal nerve in a frequency-dependent manner. The induction of cFos protein was more prominent in the contralateral PFN than in the ipsilateral PFN following horizontal semicircular canal nerve stimulation. The functional vestibulo-parafascicular connection is a neural substrate for the transmission of vestibular sensory information to the basal ganglia.

Signaling pathway of glutamate in the vestibular nuclei following acute hypotension in rats.

Acute hypotension induces excitation of electrical activity and expression of c-Fos protein and phosphorylated extracellular signal-regulated kinase (pERK) in the vestibular nuclei. Expression of c-Fos protein and pERK is mediated by the excitatory neurotransmitter, glutamate. In this study, in order to investigate the signaling pathway of glutamate in the vestibular nuclei following acute hypotension, expression of the NR2B subunit of glutamate N-methyl-D-aspartate (NMDA) receptors and the GluR1 subunit of glutamate alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors was measured by Western blotting in the medial vestibular nucleus (MVN) following acute hypotension in bilateral labyrinthectomized (BL) rats. In intact labyrinthine animals, acute hypotension increased expression of pGluR1 and pNR2B in the MVN. Expression of pGluR1 Ser831 and Ser845 peaked at 5 and 30 min after acute hypotension and expression of pNR2B peaked at 60 min after acute hypotension, respectively. In BL animals, expression of pGluR1 Ser831, pGluR1 Ser845, and pNR2B was decreased significantly compared to intact labyrinthine animals following acute hypotension. These results suggest that excitatory afferent signals from the peripheral vestibular receptors, resulting from acute hypotension, release glutamate into postsynaptic neurons in the vestibular nuclei and the excitatory signals are transmitted through the GluR1 subunit of the AMPA receptors and the NR2B subunits of the NMDA receptors in the vestibular system.

Asymmetric activation of extracellular signal-regulated kinase 1/2 in rat vestibular nuclei by unilateral labyrinthectomy.

The expression of phosphorylated extracellular signal-regulated kinase 1/2 (pERK 1/2) was evaluated in the vestibular nuclei (VN) of rats following unilateral labyrinthectomy (UL). Immunohistochemistry revealed a significant asymmetrical increase in pERK 1/2 expression in the VN, 5 min after UL, after which pERK 1/2 immunoreactivity decreased rapidly and was undetectable by 90 min after UL. These results suggest that unilateral deafferentation of the vestibular system triggers intracellular signal pathways that activate ERK 1/2 in the VN.

Immunohistochemical detection of phosphorylated form of extracellular signal-regulated kinase 1/2 in rat vestibular nuclei following hemorrhagic hypotension.

The purpose of this study was to evaluate the expression of the phosphorylated form of extracellular-regulated protein kinase 1/2 (pERK1/2), which is one of the major regulatory factors for transcription of the c-fos oncogene in neurons, within the vestibular nuclei (VN) of rats following acute arterial hypotension. Following acute arterial hypotension induced by rapid hemorrhage, a significant number of pERK1/2-immunoreactive neurons appeared bilaterally in the caudal aspect of the medial and inferior VN. No labeling of pERK1/2 was observed in the lateral VN. The peak expression of pERK1/2-immunoreactive neurons in these nuclei occurred within 5 min after hemorrhage. In bilaterally labyrinthectomized rats, the appearance of pERK1/2-immunoreactive neurons was eliminated in the VN. These results suggest that, following acute hypotension, afferent signals from the peripheral vestibular receptors are required for activation of extracellular signal-regulated kinase 1/2 in the VN.

Temporal changes of calbindin expression in the nodulus following unilateral labyrinthectomy in rats.

Following unilateral vestibular deafferentation, many of the oculomotor and postural symptoms, such as spontaneous ocular nystagmus and head tilt, gradually abate over time in a process known as 'vestibular compensation'. Although many experimental studies have indicated a role for the cerebellum during vestibular compensation, the effects of unilateral labyrinthectomy (UL) on cerebellar function and the role of cerebellum in post-lesional plasticity remain unclear. Thus, we investigated the temporal changes of calbindin expression in the ipsilateral and contralateral nodulus to the lesion side during vestibular compensation following UL in rats. Change of calbindin expression in the nodulus was measured by immunohistochemistry at 2, 6, 24 and 48hr following UL. The staining intensity of calbindin-positive Purkinje cells in the ipsilateral and contralateral nodulus to the lesion side was found to decrease 6hr after UL compared with the control and asymmetric calbindin expression between ipsilateral and contralateral nodulus 24hr after UL. Forty-eight hours after UL, calbindin expression returned to the control level, and asymmetric expression in both noduli also subsided. It is suggested that the regulation of calbindin expression may facilitate synaptic plasticity by adjusting the efficacy of biochemical responses of Purkinje cells according to the changes in neuronal activity in the vestibular nuclear complex during the early phase of vestibular compensation. Thus, the results revealed that the nodulus has a role during vestibular compensation through Purkinje cells.

Recovery of vestibulogastrointestinal symptoms during vestibular compensation after unilateral labyrinthectomy in rats.

BACKGROUND: The loss of unilateral vestibular function causes vestibulogastrointestinal symptoms that include nausea and vomiting. However, the temporal changes occurring on vestibular compensation are unclear. Thus, the temporal changes and the role of the cerebellum in the recovery of vestibulogastrointestinal symptoms after unilateral labyrinthectomy (UL) were investigated in this study. METHODS: Vestibulogastrointestinal symptoms were evaluated for intestinal transit and geometric center, whereas vestibulo-ocular symptoms were represented by spontaneous nystagmus. Expression of the c-Fos protein was observed in the vestibular nuclei. These were measured at 30 minutes and at 2, 6, and 24 hours after UL in rats. RESULTS: Intestinal transit was 66.3% +/- 7.6% in the control animals but significantly decreased to 40.7% +/- 7.8%, 46.3% +/- 6.3%, and 48.6% +/- 10.8% at 30 minutes (p < 0.01), 2 hours (p < 0.01), and 6 hours (p < 0.05) after UL, respectively. The intestinal transit showed a recovery to control levels 24 hours after UL. The geometric center was 5.6 +/- 0.4 in control animals but significantly decreased to 2.1 +/- 0.4, 2.9 +/- 0.3, and 4.0 +/- 0.3 at 30 minutes, 2 hours, and 6 hours after UL, respectively (p < 0.01). Recovery of the geometric center to control levels, 24 hours after UL, was reported. Uvulonodullectomy significantly decreased the intestinal transit and geometric center for 24 hours after surgery (p < 0.01). Moreover, UL in uvulonodullectomized animals significantly decreased the intestinal transit and geometric center for 24 hours after surgery (p < 0.01). Pretreatment of the UL animals with MK-801 significantly increased the geometric center 30 minutes after surgery (p < 0.01). Unilateral labyrinthectomy produced spontaneous nystagmus, 28.9 +/- 1.5, 23.3 +/- 1.4, 17.5 +/- 1.5, and 9.2 +/- 0.9 beats per 10 seconds at 30 minutes and at 2, 6, and 24 hours after UL, respectively. Expression of the c-Fos protein was significantly increased in the medial vestibular nuclei and inferior vestibular nuclei at 1, 2, and 6 hours after UL, and the expression was significantly decreased in animals that were pretreated with MK-801 (p < 0.01). CONCLUSION: These results suggest that the recovery of vestibulogastrointestinal symptoms is faster than that of vestibulo-ocular symptoms and that the cerebellum and glutamate have an important role to play in the recovery of symptoms after UL.

The Effects of Glutamate NMDA Receptor Antagonist MK-801 on Gastrointestinal Motility after Middle Cerebral Artery Occlusion in Rats.

This study was performed to investigate the role of glutamate neurotransmitter system on gastrointestinal motility in a middle cerebral artery occlusion (MCAO) model of rats. The right middle cerebral artery was occluded by surgical operation, and intestinal transit and geometric center as a parameter of gastrointestinal motility and expression of c-Fos protein in the insular cortex and cingulate cortex were measured at 2 and 12 h after MCAO. Intestinal transit was 66.3+/-7.5% and 62.3+/-5.7% 2 and 12 h after sham operation, respectively, and MCAO significantly decreased intestinal transit to 39.0+/-3.5% and 47.0+/-5.1% at 2 and 12 h after the occlusion, respectively (p<0.01). The geometric center was 5.6+/-0.4 and 5.2+/-0.9 at 2 and 12 h after sham operation, respectively, and MCAO significantly decreased geometric center to 2.9+/-0.8 and 3.0+/-0.3 at 2 and 12 h after the occlusion, respectively (p<0.01). In control animals, injection of atropine decreased intestinal transit to 35.9+/-5.2%, and injection of glutamate NMDA receptor antagonist, MK-801, decreased intestinal transit to 28.8+/-9.5%. Pretreatment with MK-801, a glutamate NMDA receptor antagonist, in the MCAO group decreased intestinal transit to 11.8+/-3.2%, which was significantly decreased compared to MCAO group (p<0.01). MCAO markedly increased the expression of c-Fos protein in the insular cortex and cingulate cortex ipsilateral to the occlusion 2 h after MCAO, and pretreatment with MK-801 produced marked reduction of c-Fos protein expression compared to MCAO group (p<0.01). These results suggest that modulation of gastrointestinal motility after MCAO might be partially mediated through a glutamate NMDA receptor system.