Localisation of 11β-Hydroxysteroid Dehydrogenase Type 2 in Mineralocorticoid Receptor Expressing Magnocellular Neurosecretory Neurones of the Rat Supraoptic and Paraventricular Nuclei

© 2015 British Society for Neuroendocrinology. An accumulating body of evidence suggests that the activity of the mineralocorticoid, aldosterone, in the brain via the mineralocorticoid receptor (MR) plays an important role in the regulation of blood pressure. MR was recently found in vasopressin and oxytocin synthesising magnocellular neurosecretory cells (MNCs) in both the paraventricular (PVN) and supraoptic (SON) nuclei in the hypothalamus. Considering the physiological effects of these hormones, MR in these neurones may be an important site mediating the action of aldosterone in blood pressure regulation within the brain. However, aldosterone activation of MR in the hypothalamus remains controversial as a result of the high binding affinity of glucocorticoids to MR at substantially higher concentrations compared to aldosterone. In aldosterone-sensitive epithelia, the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) prevents glucocorticoids from binding to MR by converting glucocorticoids into inactive metabolites. The present study aimed to determine whether 11β-HSD2, which increases aldosterone selectivity, is expressed in MNCs. Specific 11β-HSD2 immunoreactivity was found in the cytoplasm of the MNCs in both the SON and PVN. In addition, double-fluorescence confocal microscopy demonstrated that MR-immunoreactivity and 11β-HSD2-in situ hybridised products are colocalised in MNCs. Lastly, single-cell reverse transcriptase-polymerase chain reaction detected MR and 11β-HSD2 mRNAs from cDNA libraries derived from single identified MNCs. These findings strongly suggest that MNCs in the SON and PVN are aldosterone-sensitive neurones

Spike patterning in oxytocin neurons:Capturing physiological behaviour with Hodgkin-Huxley and integrate-and-fire models

Integrate-and-fire (IF) models can provide close matches to the discharge activity of neurons, but do they oversimplify the biophysical properties of the neurons? A single compartment Hodgkin-Huxley (HH) model of the oxytocin neuron has previously been developed, incorporating biophysical measurements of channel properties obtained in vitro. A simpler modified integrate-and-fire model has also been developed, which can match well the characteristic spike patterning of oxytocin neurons as observed in vivo. Here, we extended the HH model to incorporate synaptic input, to enable us to compare spike activity in the model with experimental data obtained in vivo. We refined the HH model parameters to closely match the data, and then matched the same experimental data with a modified IF model, using an evolutionary algorithm to optimise parameter matching. Finally we compared the properties of the modified HH model with those of the IF model to seek an explanation for differences between spike patterning in vitro and in vivo. We show that, with slight modifications, the original HH model, like the IF model, is able to closely match both the interspike interval (ISI) distributions of oxytocin neurons and the observed variability of spike firing rates in vivo and in vitro. This close match of both models to data depends on the presence of a slow activity-dependent hyperpolarisation (AHP); this is represented in both models and the parameters used in the HH model representation match well with optimal parameters of the IF model found by an evolutionary algorithm. The ability of both models to fit data closely also depends on a shorter hyperpolarising after potential (HAP); this is explicitly represented in the IF model, but in the HH model, it emerges from a combination of several components. The critical elements of this combination are identified

Thermal Shock Resistances of High Thermal Conductivity C/C-Composite as Plasma Facing Materials for Fusion Reactor Devices

The thermal shock resistances, mechanical and fracture mechanics properties of one directionally oriented carbon fiber reinforced carbon composite HUD-1S, which was recently developed as a plasma facing material for fusion reactor devices, are presented. These results are compared with the cases of a fine grain isotropic graphite PD-600S. HUD-1S has extremely high anisotropies, such as the thermal conductivity in the direction along the fiber orientation is extremely high in excess of the conductivity of copper or silver. But the conductivitics of normal directions are below a half of the case of graphite. The characteristic isotropies on the thermal shock resistances and fracture toughnesses of this composite are given quantitatively

Tensor polarization of 12^{12}C[ 21+^+_1] in the 16^{16}O(13^{13}C,12^{12}C)17^{17}O reaction at 50 MeV

The $^{16}$O($^{13}$C,$^{12}$C)$^{17}$O reaction at 50 MeV has been investigated using the kinematical coincidence method. Polarization tensors $t_{20}$ and $t_{40}$ of $^{12}$C[ 2$^+_1$] for the quantization axis taken along the direction of propagation have been measured by analyzing the energy spectrum of $^{12}$C[ 2$^+_1$] , modulated by the effect of $\gamma$ ray emission. The deduced $t_{40}$ values significantly deviate from zero, contrary to the prediction of the distorted-wave Born approximation theory based on one-step $p$ shell neutron stripping without spin-dependent interactions. The phenomenological spin–orbit interaction necessary to reproduce the magnitude of measured $t_{40}$ is found to be much larger than the folding model prediction. It is shown that the experimental polarization tensors as well as the cross sections can be reproduced by introducing multi-step processes involving excitations in $^{12}$C and $^{13}$C without introducing spin-dependent interactions

Trpm4 Ion Channels in pre-Bo¨tzinger Complex Interneurons Are Essential for Breathing Motor Pattern But Not Rhythm

Inspiratory breathing movements depend on pre-Bötzinger complex (preBötC) interneurons that express calcium (Ca2+)-activated nonselective cationic current (ICAN) to generate robust neural bursts. Hypothesized to be rhythmogenic, reducing ICAN is predicted to slow down or stop breathing; its contributions to motor pattern would be reflected in the magnitude of movements (output). We tested the role(s) of ICAN using reverse genetic techniques to diminish its putative ion channels Trpm4 or Trpc3 in preBötC neurons in vivo. Adult mice transduced with Trpm4-targeted short hairpin RNA (shRNA) progressively decreased the tidal volume of breaths yet surprisingly increased breathing frequency, often followed by gasping and fatal respiratory failure. Mice transduced with Trpc3-targeted shRNA survived with no changes in breathing. Patch-clamp and field recordings from the preBötC in mouse slices also showed an increase in the frequency and a decrease in the magnitude of preBötC neural bursts in the presence of Trpm4 antagonist 9-phenanthrol, whereas the Trpc3 antagonist pyrazole-3 (pyr-3) showed inconsistent effects on magnitude and no effect on frequency. These data suggest that Trpm4 mediates ICAN, whose influence on frequency contradicts a direct role in rhythm generation. We conclude that Trpm4-mediated ICAN is indispensable for motor output but not the rhythmogenic core mechanism of the breathing central pattern generator