Inhibitory Synaptic Transmission Differs in Mouse Type A and B Medial Vestibular Nucleus Neurons In Vitro

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.

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.


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.


2001 ◽  
Vol 40 (6) ◽  
pp. 806-817 ◽  
Author(s):  
Karen A Maubach ◽  
Karine Martin ◽  
David W Smith ◽  
Louise Hewson ◽  
Robert A Frankshun ◽  
...  

Blood ◽  
1979 ◽  
Vol 54 (6) ◽  
pp. 1395-1399 ◽  
Author(s):  
JW Singer ◽  
PJ Fialkow ◽  
LW Dow ◽  
C Ernst ◽  
L Steinmann

Abstract The assumption that human granulocyte-macrophage colonies have a unicellular origin and thus are true clones has been directly tested. Cells from seven females heterozygous for the common glucose-6- phosphate dehydrogenase (G-6-PD) gene (GdB) and the variant GdA were cultured in semisolid medium for granulocyte-macrophage colony growth and the enzyme type of individual colonies was determined. When the colony density was less than 20/dish, more than 95% of colonies had either type A or type B G-6-PD, but not both. At colony densities greater than 30/dish, between 15% and 75% of colonies had both enzyme types and therefore arose from more than one cell. These results are consistent with a unicellular origin for the colonies only when they are cultured at low densities. With increasing colony density, there was a greater frequency of colonies with both type A and type B activity, suggesting that accurate enumeration of committed stem cells can only be performed at low colony concentrations.


2013 ◽  
Vol 9 (1) ◽  
pp. 20121049 ◽  
Author(s):  
Natalia L. Komarova ◽  
Daniela Anghelina ◽  
Igor Voznesensky ◽  
Benjamin Trinité ◽  
David N. Levy ◽  
...  

Human immunodeficiency virus can spread through target cells by transmission of cell-free virus or directly from cell-to-cell via formation of virological synapses. Although cell-to-cell transmission has been described as much more efficient than cell-free infection, the relative contribution of the two transmission pathways to virus growth during multiple rounds of replication remains poorly defined. Here, we fit a mathematical model to previously published and newly generated in vitro data, and determine that free-virus and synaptic transmission contribute approximately equally to the growth of the virus population.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2120-2120
Author(s):  
Majed A. Refaai ◽  
Neil Blumberg ◽  
Charles W. Francis ◽  
Richard Phipps ◽  
Sherry Spinelli ◽  
...  

Abstract Abstract 2120 Poster Board II-97 Background: Transfusion of ABO non-identical red blood cells (RBCs) can cause immune mediated hemolytic transfusion reactions. Therefore, only ABO identical RBCs are transfused, except in emergencies, when group O RBCs are transfused. Use of exclusively ABO identical plasma and platelet (PLT) transfusions is not uniformly practiced nor always feasible despite reports of hemolytic reactions. Since PLTs and soluble plasma proteins possess A and B antigens, ABO non-identical PLTs could, theoretically, be activated and/or rendered hypofunctional by anti-A and anti-B antibodies (Abs) in transfused or recipient plasma. Recent findings demonstrate that transfusion of ABO non-identical PLTs is associated with increased bleeding in surgical patients and patients with leukemia. Blunt trauma patients who received at least one ABO non-identical blood product transfusion demonstrated a significantly higher RBC usage (12.3 ± 6.9 SD versus 8.4 ± 9.9 SD, p-value 0.0011) compared to those patients who received only ABO identical transfusions (Transfusion. 2007;47:192A). ABO identical PLT transfusions in leukemia patients were a significant predictor of survival (Leukemia. 2008;22:631-5). In a multi center retrospective analysis of more than one million cancer patients over a period of 9 years, Khorana et al. demonstrated an overall venous thromboembolism (VTE) rate of 4.1%. In multivariate risk factor analysis, the association between blood transfusions and VTE had an odds ratio of 1.35 (1.31-1.39, 95% CI) with a p value of < 0.001 (Arch Intern Med. 2008;168:2377-81). We hypothesized that PLTs activated by ABO Abs might have altered function. Methods and Materials: PLT function was evaluated by testing aggregation in platelet rich plasma (PRP). Aggregation was performed with PRP from 7 type A and 6 type B normal blood donors following a 10 min incubation period at 37°C with either normal saline, group O or AB plasma. PLTs were activated by 20 mM ADP and aggregation quantitated from the maximum change in OD. Similar experiments were repeated utilizing different titration of the commercial anti-A and anti-B anti-sera. Results: Following incubation with O plasma, PLT aggregation was inhibited by a mean of 38% and 18% for group A and B PLTs, respectively (P ≤ 0.005) (Figure). A trend toward inhibition was observed when type A PLTs were incubated with control AB plasma (average of 14%, P = 0.187), whereas type B PLT showed no inhibition when incubated with AB plasma (P = 0.939) (Table 1). PLT aggregation with the anti-sera showed gradual inhibition correlated with the antibody titer (Table 2). Conclusion: Mediators in group O plasma, most likely anti-A and anti-B Abs, cause impaired PLT aggregation in ABO non-identical PLTs. These in vitro findings may explain, at least in part, clinical observations that patients receiving ABO non-identical PLT transfusions experience more bleeding than recipients of ABO identical PLT transfusions. Table 1: PLT aggregation of A and B PRP with saline, O and AB plasma. Blood Donor Type N Average Percentage of Platelet Aggregation (SD) Normal Saline “O” Plasma P value* “AB” Plasma P value A 7 92 (7.4) 54 (9.9) < 0.005 78 (2.9) 0.187 B 6 85 (6.8) 67 (9.8) 0.005 85.3 (7.9) 0.939 P value < 0.05 is considered statistically significant. Figure: PLT function of type A PRP incubated for 10 min at 37°C with O or AB plasma, or normal saline. Figure:. PLT function of type A PRP incubated for 10 min at 37°C with O or AB plasma, or normal saline. Table 2: PLT aggregation of A and B PRP with different titration of the commercial anti-A and anti-B anti-sera. Anti-sera/Plasma Type A PRP P value Type B PRP P value Baseline 93.7 (3.1) — 83.4 (11) — 1:1024 48.7 (8.5) 0.006 36.3 (7.8) 0.0005 1:512 57.3 (2.5) 0.0001 47.7 (7.5) 0.002 1:256 59.5 (3.5) 0.008 59.5 (0.7) 0.002 1:128 55.5 (3.5) 0.006 67 (2.8) 0.027 AB plasma 87.7 (3.2) 0.08 81.2 (16) 0.88 Disclosures: No relevant conflicts of interest to declare.


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