Long-Term Plasticity of Ipsilesional Medial Vestibular Nucleus Neurons After Unilateral Labyrinthectomy

2003 ◽  
Vol 90 (1) ◽  
pp. 184-203 ◽  
Author(s):  
Mathieu Beraneck ◽  
Mohammed Hachemaoui ◽  
Erwin Idoux ◽  
Laurence Ris ◽  
Atsuhiko Uno ◽  
...  

Unilateral labyrinthectomy results in oculomotor and postural disturbances that regress in a few days during vestibular compensation. The long-term (after 1 mo) consequences of unilateral labyrinthectomy were investigated by characterizing the static and dynamic membrane properties of the ipsilesional vestibular neurons recorded intracellularly in guinea pig brain stem slices. We compared the responses of type A and type B medial vestibular nucleus neurons identified in vitro to current steps and ramps and to sinusoidal currents of various frequencies. All ipsilesional vestibular neurons were depolarized by 6–10 mV at rest compared with the cells recorded from control slices. Both their average membrane potential and firing threshold were more depolarized, which suggests that changes in active conductances compensated for the loss of excitatory afferents. The afterhyperpolarization and discharge regularity of type B but not type A neurons were increased. All ipsilesional vestibular cells became more sensitive to current injections over a large range of frequencies (0.2–30 Hz), but this increase in sensitivity was greater for type B than for type A neurons. This was associated with an increase of the peak frequency of linear response restricted to type B neurons, from 4–6 to 12–14 Hz. Altogether, we show that long-term vestibular compensation involves major changes in the membrane properties of vestibular neurons on the deafferented side. Many of the static and dynamic membrane properties of type B neurons became more similar to those of type A neurons than in control slices, leading to an increase in the overall homogeneity of medial vestibular nucleus neurons.

2003 ◽  
Vol 90 (3) ◽  
pp. 1689-1703 ◽  
Author(s):  
Atsuhiko Uno ◽  
Erwin Idoux ◽  
Mathieu Beraneck ◽  
Pierre-Paul Vidal ◽  
Lee E. Moore ◽  
...  

In vitro intracellular recordings of central vestibular neurons have been restricted so far to the medial vestibular nucleus (MVN). We performed intracellular recordings of large Deiters' neurons in the lateral vestibular nucleus (LVN) to determine their static and dynamic membrane properties, and compare them with those of type A and type B neurons identified in the MVN. Unlike MVN neurons (MVNn), the giant-size LVN neurons (LVNn) form a homogeneous population of cells characterized by sharp spikes, a low-amplitude, biphasic after-hyperpolarization like type B MVNn, but also an A-like rectification like type A MVNn. In accordance with their lower membrane resistance, the sensitivity of LVNn to current injection was lower than that of MVNn over a large range of frequencies. The main difference between LVNn and MVNn was that the Bode plots showing the sensitivity of LVNn as a function of stimulation frequency were flatter than those of MVNn, and displayed a weaker resonance. Furthermore, most LVNn did not show a gradual decrease of their firing rate modulation in the frequency range where it was observed in MVNn. LVNn synchronized their firing with the depolarizing phase of high-frequency sinusoidal current injections. In vivo studies have shown that the MVN would be mainly involved in gaze control, whereas the giant LVNn that project to the spinal cord are involved in the control of posture. We suggest that the difference in the membrane properties of LVNn and MVNn may reflect their specific physiological roles.


2004 ◽  
Vol 92 (3) ◽  
pp. 1668-1684 ◽  
Author(s):  
Mathieu Beraneck ◽  
Erwin Idoux ◽  
Atsuhiko Uno ◽  
Pierre-Paul Vidal ◽  
Lee E. Moore ◽  
...  

Vestibular compensation after a unilateral labyrinthectomy leads to nearly complete disappearance of the static symptoms triggered by the lesion. However, the dynamic vestibular reflexes associated with head movements remain impaired. Because the contralesional labyrinth plays a prominent role in the generation of these dynamic responses, intracellular recordings of contralesional medial vestibular nucleus neurons (MVNn) were done after 1 mo of compensation. Their firing properties and cell type were characterized at rest, and their response dynamics investigated using step, ramp, and sinusoidal current stimulations. The sensitivity of the contralesional MVNn firing rates to applied current was increased, which, along with increased phase leads, suggests that significant changes in active conductances occurred. We found an increased proportion of the phasic type B neurons relative to the tonic type A neurons in the contralesional MVN. In addition, the remaining contralesional type A MVNn response dynamics tended to approach those of type B MVNn. Thus the contralesional MVNn in general showed more phasic response dynamics than those of control MVNn. Altogether, the firing properties of MVNn are differentially modified on the ipsilesional and contralesional sides of the brain stem 1 mo after unilateral labyrinthectomy. Ipsilesional MVNn acquire more “type A–like” tonic membrane properties, which would contribute to the stabilization of the spontaneous activity that recovers in the deafferented neurons during vestibular compensation. The bilateral increase in the sensitivity of MVNn and the acquisition of more “B-like” phasic membrane properties by contralesional MVNn should promote the restoration of the vestibular reflexes generated by the remaining, contralesional labyrinth.


2003 ◽  
Vol 123 (2) ◽  
pp. 182-186 ◽  
Author(s):  
Vito Enrico Pettorossi ◽  
Mayank Dutia ◽  
Adele Frondaroli ◽  
Cristina Dieni ◽  
Silvarosa Grassi

2021 ◽  
Vol 11 (3) ◽  
pp. 360
Author(s):  
Junya Fukuda ◽  
Kazunori Matsuda ◽  
Go Sato ◽  
Tadashi Kitahara ◽  
Momoyo Matsuoka ◽  
...  

Background: Vestibular compensation (VC) after unilateral labyrinthectomy (UL) consists of the initial and late processes. These processes can be evaluated based on the decline in the frequency of spontaneous nystagmus (SN) and the number of MK801-induced Fos-positive neurons in the contralateral medial vestibular nucleus (contra-MVe) in rats. Histamine H3 receptors (H3R) are reported to be involved in the development of VC. Objective: We examined the effects of betahistine, an H3R antagonist, on the initial and late processes of VC in UL rats. Methods: Betahistine dihydrochloride was continuously administered to the UL rats at doses of 100 and 200 mg/kg/day using an osmotic minipump. MK801 (1.0 mg/kg) was intraperitoneally administered on days 7, 10, 12, and 14 after UL, while Fos-positive neurons were immunohistochemically stained in the contra-MVe. Results: The SN disappeared after 42 h, and continuous infusion of betahistine did not change the decline in the frequency of SN. The number of MK801-induced Fos-positive neurons in contra-MVe significantly decreased on days 7, 10, and 12 after UL in a dose-dependent manner in the betahistine-treated rats, more so than in the saline-treated rats. Conclusion: These findings suggest that betahistine facilitated the late, but not the initial, process of VC in UL rats.


2006 ◽  
Vol 95 (5) ◽  
pp. 3208-3218 ◽  
Author(s):  
Aaron J. Camp ◽  
Robert J. Callister ◽  
Alan M. Brichta

Fast inhibitory synaptic transmission in the medial vestibular nucleus (MVN) is mediated by GABAA receptors (GABAARs) and glycine receptors (GlyRs). To assess their relative contribution to inhibition in the MVN, we recorded miniature inhibitory postsynaptic currents (mIPSCs) in physiologically characterized type A and type B MVN neurons. Transverse brain stem slices were prepared from mice (3–8 wk old), and whole cell patch-clamp recordings were obtained from visualized MVN neurons (CsCl internal; Vm = –70 mV; 23°C). In 81 MVN neurons, 69% received exclusively GABAAergic inputs, 6% exclusively glycinergic inputs, and 25% received both types of mIPSCs. The mean amplitude of GABAAR-mediated mIPSCs was smaller than those mediated by GlyRs (22.6 ± 1.8 vs. 35.3 ± 5.3 pA). The rise time and decay time constants of GABAAR- versus GlyR-mediated mIPSCs were slower (1.3 ± 0.1 vs. 0.9 ± 0.1 ms and 10.5 ± 0.3 vs. 4.7 ± 0.3 ms, respectively). Comparison of type A ( n = 20) and type B ( n = 32) neurons showed that type A neurons received almost exclusively GABAAergic inhibitory inputs, whereas type B neurons received GABAAergic inputs, glycinergic inputs, or both. Intracellular labeling in a subset of MVN neurons showed that morphology was not related to a MVN neuron's inhibitory profile ( n = 15), or whether it was classified as type A or B ( n = 29). Together, these findings indicate that both GABA and glycine contribute to inhibitory synaptic processing in MVN neurons, although GABA dominates and there is a difference in the distribution of GABAA and Gly receptors between type A and type B MVN neurons.


2007 ◽  
Vol 16 (4-5) ◽  
pp. 171-177
Author(s):  
Adrian Lozada ◽  
Kaj Karlstedt ◽  
Pertti Panula ◽  
Antti A. Aarnisalo

In the auditory periphery, GDNF has been shown to have a trophic effect to spiral ganglion neurons, both during development and in adult animals. We have studied the effect of unilateral labyrinthectomy (UL) on protein levels and expression of GDNF multicomponent receptor complex: the ret tyrosine kinase and coreceptor GFRα-1 in the medial vestibular nucleus of the adult rat. GFRα-1 protein levels display an increasing trend in ipsilateral medial vestibular nucleus culminating at 48 h post UL. On the other hand, GFRα-1 mRNA expression levels in ipsi- and contralateral medial vestibular nucleus show a steadily decreasing trend that is significant at 1 week post-lesion. Protein levels for c-Ret isoforms also show an initial bilateral decreasing trend that ceases at 48 h in ipsilateral medial vestibular nucleus but persists on the contralateral side. c-Ret mRNA expression levels show a significant decrease at 4 h post UL followed by another significant decrease 1 week post UL. Our data would suggest that neurotrophins belonging to the GDNF family are involved in this model of post-lesional CNS plasticity.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Fred I Chasalow ◽  
Ron Bochner

Abstract Background: In 1987, Graves observed that during the 3rd trimester, some patients with pre-eclampsia had high levels of unknown materials that could be detected with assays for digoxin (DLM). In 2018, we characterized a new candidate for the DLM, Ionotropin. It is a phosphocholine (PC) ester of a novel steroid with 23 carbon atoms. As Ionotropin shares structural features (a) with spironolactone (both have spiral lactones in the E-ring) and (b) with digoxin (E-ring lactone and 3α-5β configuration), we have proposed that Ionotropin may function as a potassium (K+) sparing diuretic. This suggestion is supported by the observations that [1] patients who cannot make Ionotropin (7-dehydrosterol reductase deficiency) are K+ wasting and [2] breast cyst fluids with high K+ levels also have high Ionotropin levels. Hypothesis: During the 3rd trimester, fetal requirements for K+ reach a maximum, fetal blood pressure increases and aldosterone signaling is blocked. This blockage leads to fetal sodium (Na+) wasting and is essential for formation of amniotic fluid. These events are consistent with a normal role for an unknown endogenous K+ sparing hormone and would be the basis for a modest elevation of maternal DLM during the 3rd trimester. Our hypothesis is that if any of the functions were inadequate, then the fetal-placental unit would synthesize excess PC-spiral steroids; the woman would exhibit symptoms of K+ sparing hormone excess (hypertension and proteinuria) and would be diagnosed with pre-eclampsia. Experimental Results: We have just reported a pilot study associating elevated PC esters of spiral steroids in women with pre-eclampsia. In brief, 12 of 19 women had elevated levels of at least one of the PC steroids (Z-score > 2) when compared to the levels in 20 pregnant women matched for gestational age and fetal sex. There are two basic mechanisms for this dichotomy: (a) there may be episodic secretion with of a DLM with a short half-life or (b) there may be two different underlying biochemical causes. In prior studies, there has been no indication of episodic secretion of DLM similar to that observed with glucocorticoids, Ionotropin or other PC spiral steroids. Discussion: There are two basic types of K+ sparing diuretics. Type A: Spironolactone functions by regulating the NaK-ATPase. Type B: Triamterene functions by blocking synthesis of epithelial Na+ channels. Thus, Type A would have high levels of spiral steroids and Type B would have low levels of spiral steroids. Type A patients would be expected to have higher risk of long-term consequences when compared to the Type B patients. Conclusion: The recognition of the division of pre-eclampsia into two separate diseases might be the key observation for developing Type-specific diagnosis and therapy. For example, a Type A patient might benefit from a low salt diet but that diet would not be expected to benefit a patient with Type B disease.


2019 ◽  
Vol 40 (32) ◽  
pp. 2727-2736 ◽  
Author(s):  
Jung-Min Ahn ◽  
Hoyun Kim ◽  
Osung Kwon ◽  
Sang Yong Om ◽  
Ran Heo ◽  
...  

Abstract Aims To evaluate the acute and long-term prognosis of acute aortic syndrome (AAS) according to the disease entity [intramural haematoma (IMH) vs. aortic dissection (AD)] and the anatomical location (type A vs. B). Methods and results A total of 1012 patients [672 with AD and 340 with IMH (33.6%)] were enrolled between 1993 and 2015. Compared with AD patients, IMH patients were older and had higher frequency of female sex and distal aorta involvement. The overall crude in-hospital mortality of AAS was 8.6%; type A AD [15.0%; adjusted hazard ratio (aHR) 30.4; 95% confidence interval (CI) 8.62–107.3; P < 0.001], type A IMH (8.0%; aHR 4.85; 95% CI 1.29–18.2; P = 0.019), type B AD (5.0%; aHR 3.51; 95% CI 1.00–12.4; P = 0.051), and type B IMH [1.5%; aHR 1.00 (reference)]. During a median follow-up duration of 8.5 years (interquartile range: 4.0–13.5 years), AD (aHR 2.78; 95% CI 1.87–4.14; P < 0.001) and type A (aHR 2.28; 95% CI 1.45–3.58; P < 0.001) was associated with a higher risk of aortic death. After 90 days, a risk of aortic death was no longer associated with anatomical location (aHR 0.74; 95% CI 0.40–1.36; P = 0.33), but remained associated with disease entity (aHR 1.83; 95% CI 1.10–3.04; P = 0.02). Conclusion The clinical features, response to treatment strategy, and outcomes of IMH patients were distinct from those of AD patients. Both early and late survival was better for IMH than for AD. In addition to the anatomical location of AAS, the disease entity is an independent factor associated with both acute and long-term mortality in patients with AAS. Further investigation is necessary to confirm the prognostic implication of disease entity in different patient populations.


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