Decreased Immunoreactivities and Functions of the Chloride Transporters, KCC2 and NKCC1, in the Lateral Superior Olive Neurons of Circling Mice

Objectives. We tested the possibility of differential expression and function of the potassium-chloride (KCC2) and sodium-potassium-2 chloride (NKCC1) co-transporters in the lateral superior olive (LSO) of heterozygous (+/cir) or homozygous (cir/cir) mice.Methods. Mice pups aged from postnatal (P) day 9 to 16 were used. Tails from mice were cut for DNA typing. For Immunohistochemical analysis, rabbit polyclonal anti-KCC2 or rabbit polyclonal anti-NKCC1 was used and the density of immunolabelings was evaluated using the NTH image program. For functional analysis, whole cell voltage clamp technique was used in brain stem slices and the changes of reversal potentials were evaluated at various membrane potentials.Results. Immunohistochemical analysis revealed both KCC2 and NKCC1 immunoreactivities were more prominent in heterozygous (+/cir) than homozygous (cir/cir) mice on P day 16. In P9-P12 heterozygous (+/cir) mice, the reversal potential (E(gly)) of glycine-induced currents was shifted to a more negative potential by 50 mu M bumetanide, a known NKCC1 blocker, and the negatively shifted EA, was restored by additional application of 1 mM furosemide, a KCC2 blocker (-58.9 +/- 2.6 mV to -66.0 +/- 1.5 mV [bumetanide], -66.0 1.5 mV to -59.8 +/- 2.8 mV [furosemide+bumetanide], n=11). However, only bumetanide was weakly, but significantly effective (-60.1 +/- 2.9 mV to -62.7 +/- 2.6 mV [bumetanide], -62.7 +/- 2.6 mV to -62.1 +/- 2.5 mV [furosernide+bumetanide], n=7) in P9-P12 homozygous (cir/cir) mice.Conclusion. The less prominent immunoreactivities and weak or absent responses to bumetanide or furosemide suggest impaired function or delayed development of both transporters in homozygous (cir/cir) mice

Exact travelling wave solutions of a variety of Boussinesq-like equations

In this paper, we obtain exact traveling wave solutions of a variety of Boussinesq-like equations by using two distinct methods with symbolic computation. The Boussinesq equations play an important role in physical applications, such as in nonlinear lattice waves, acoustic waves, iron sound waves in a plasma, and vibrations in a nonlinear string. More precisely, the modified tanh-coth method is employed to obtain single soliton solutions, and the extended Jacobi elliptic function method is applied to derive doubly periodic wave solutions. Further, it is shown that soliton solutions and triangular solutions can be established as the limits of the Jacobi doubly periodic wave solutions. The employed approaches are quite efficient for the determination of the solutions, and are practically well suited for solving nonlinear evolution equations arising in physics

Exact travelling wave solutions for some important nonlinear physical models

The two-dimensional nonlinear physical models and coupled nonlinear systems such as Maccari equations, Higgs equations and Schrodinger-KdV equations have been widely applied in many branches of physics. So, finding exact travelling wave solutions of such equations are very helpful in the theories and numerical studies. In this paper, the Kudryashov method is used to seek exact travelling wave solutions of such physical models. Further, three-dimensional plots of some of the solutions are also given to visualize the dynamics of the equations. The results reveal that the method is a very effective and powerful tool for solving nonlinear partial differential equations arising in mathematical physics

Direct approach for solving nonlinear evolution and two-point boundary value problems

Time-delayed nonlinear evolution equations and boundary value problems have a wide range of applications in science and engineering. In this paper, we implement the differential transform method to solve the nonlinear delay differential equation and boundary value problems. Also, we present some numerical examples including time-delayed nonlinear Burgers equation to illustrate the validity and the great potential of the differential transform method. Numerical experiments demonstrate the use and computational efficiency of the method. This method can easily be applied to many nonlinear problems and is capable of reducing the size of computational work

Neurophysiological Mechanisms Underlying Cortical Hyper-Excitability in Amyotrophic Lateral Sclerosis: A Review

Amyotrophic lateral sclerosis (ALS) is a progressive neuromotor disease characterized by the loss of upper and lower motor neurons (MNs), resulting in muscle paralysis and death. Early cortical hyper-excitability is a common pathological process observed clinically and in animal disease models. Although the mechanisms that underlie cortical hyper-excitability are not completely understood, the molecular and cellular mechanisms that cause enhanced neuronal intrinsic excitability and changes in excitatory and inhibitory synaptic activity are starting to emerge. Here, we review the evidence for an anterograde glutamatergic excitotoxic process, leading to cortical hyper-excitability via intrinsic cellular and synaptic mechanisms and for the role of interneurons in establishing disinhibition in clinical and experimental settings. Understanding the mechanisms that lead to these complex pathological processes will likely produce key insights towards developing novel therapeutic strategies to rescue upper MNs, thus alleviating the impact of this fatal disease

Glycine-induced currents are insensitive to the glycine receptor alpha(1) subunit-specific blocker, cyanotriphenylborate, in older circling mice

The pharmacologic characteristics of glycine receptors (GlyRs) in the lateral superior olive (LSO) of circling mice, animal model for inherited deafness, were investigated using a GlyR alpha(1) subunit-specific receptor blocker (cyanotriphenylborate [CTB]). There was a statistically significant age-dependent increase in the antagonistic effect of CTB in heterozygous (+/cir) mice. In postnatal (P)0-P3 heterozygous (+/cir) mice, glycine currents evoked by glycine puffs were reduced to 20.4 +/- 2.6, 37.1 +/- 3.1, and 63.9 +/- 2.5% at 0.1, 1, and 10 mu M CTB (n = 13) compared to controls, while the glycine currents were reduced to 22.3 +/- 3.5, 52.9 +/- 4.1, and 78.3 +/- 3.5% at 0.1, 1, and 10 mu M CTB (n = 7) in P8-P12 heterozygous (+/cir) mice. In contrast, the antagonistic effect of CTB was not strong and even less than that of younger animals in older homozygous (cir/cir) mice. In P0-P3 homozygous (cir/cir) mice, the extent of inhibition was 20.2 +/- 3.7, 37.8 +/- 4.3, and 66.8 +/- 4.2% at 0.1, 1, and 10 mu M CTB (n = 6) compared to controls, while the extent of inhibition was 18.7 +/- 2.4, 28.1 +/- 3.9, and 39.1 +/- 8.2% (n = 6) in P8-P12 homozygous (cir/cir) mice. The age-dependent decrease in the antagonistic effect of CTB indicates the abnormal development of the alpha(1) subunit-containing GlyRs in homozygous (cir/cir) mice

Long term depression of MNTB-LSO synapses is expressed postsynaptically in developing circling mice

Early onset long term depression (LTD) during the first postnatal week has rarely been demonstrated at the medial nucleus of trapezoid body (MNTB) - lateral superior olive (LSO) synapses in spite of many favorable conditions, such as depolarizing synapses and glutamate co-release from MNTB terminals. Thus, we tested the early expression of LTD at MNTB-LSO synapses during the first postnatal week using circling mice, whose main transmitter is glutamate at MNTB-LSO synapses. Tetanic stimulation on MNTB elicited LTD of postsynaptic currents recorded at LSO neurons in P0-P3 homozygous (cir/cir) mice (45.8 +/- 0.3% of the control, n = 7) and heterozygous (+/cir) mice (43.3 +/- 0.4% of the control, n = 7). The magnitude of LTD decreased in P8-P12 heterozygous (+/cir) mice (84.5 +/- 0.3% of the control, n = 7), but was maintained in P8-P12 homozygous (cir/cir) mice (38.2 +/- 0.3% of the control, n = 9). Glutamatergic LTD observed in homozygous (cir/cir) mice and glycinergic LTD observed heterozygous (+/cir) mice showed similar pattern of change. As currents induced by the pressure application of glycine on LSO neurons were reduced by tetanic stimulation in P0-P3 heterozygous (+/cir)mice, LTD was thought to occur at postsynaptic sites. Our results suggest that LTD might occur in vivo and participate in the synaptic silencing and strengthening of MNTB-LSO synapses, which is most active during the first postnatal week. (C) 2012 Elsevier Ireland Ltd. All rights reserved