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Notes: Large-current steps have been found in the I/V characteristics of superconducting tunnel elements that are integrated within fixed tuning structures. The Josephson frequency at the steps corresponds to the operation frequencies of the different tuning structures at 345, 460, or 600 GHz. Therefore, these current steps are interpreted as resonance effects generated by an internal interaction of the Josephson oscillation with the tuning structure. The result of a spectrometer measurement around 350 GHz is in very good agreement with the resonance frequency obtained from the I/V characteristic. This confirms the interpretation of the current steps. A simple dc measurement is therefore sufficient to determine the actual resonance frequency of the tuning structure. It may be shifted with respect to the expected frequency, due to deviations of the junction size or other parameters from their required values. The exact knowledge of the resonance frequency is important for the application of these integrated tunnel elements as mixers in radioastronomical receivers. In single junctions a splitting of the resonance step into several branches was observed, whereas in two-junction arrays a splitting into two distinct states was found. Irregular switching appeared between these two states. The temperature and magnetic-field dependence of the current steps was investigated.

Notes: The normal state resistance of Pb/Bi/In-oxide-Pb/Bi and Pb/Bi/In-oxide-Ag can be changed by applying sufficiently high voltage across the oxide barrier. To explain this effect we discuss an electrical dipole, a donor, a metal ion, and an oxygen migration model. The oxygen migration model best accounts for the experimental observations. Our investigations include telegraph noise measurements. A significant change in the low-frequency noise spectrum before and after electrical forming is found. It is possible to create and destroy two-level signals by applying an electric field on the order of 2.5×108 V/m.

Notes: The increase of the normal-state resistance of Nb-Al/AlOx-Nb tunnel junctions by annealing at elevated temperatures is reported. Junctions with an area of 4 μm2 or smaller have been investigated. The resistance could be increased up to a factor of 5 with only a small influence on the quality of the quasiparticle characteristic. The effect can be used to adjust the resistance after fabrication. The increase of the AlOx barrier thickness has been estimated. Annealing experiments in nitrogen atmosphere and after nitridation have been carried out in order to find out from where the additional oxygene stems. The annealing properties of anodization curves have been investigated. A clear increase of the oxide peak could be observed. The results also show that the resistance is sensitive to temperature increases in the various fabrication steps.

Notes: Inherited congenital myoclonus (ICM) of Poll Hereford cattle is a neurological disease in which there are severe alterations in spinal cord glycine-mediated neurotransmission. There is a specific and marked decrease, or defect, in glycine receptors and a significant increase in neuronal (synaptosomal) glycine uptake. Here we have examined the characteristics of the cerebral γ-aminobutyric acid (GABA) receptor complex, and demonstrate that the malfunction of the spinal cord inhibitory system is accompanied by a change in the major inhibitory system in the cerebral cortex. In synaptic membrane preparations from ICM calves, both high- and low-affinity binding sites for the GABA agonist [3H]muscimol were found (KD= 9.3 ± 1.5 and 227 ± 41 nM, respectively), whereas only the high-affinity site was detectable in controls (KD= 14.0 ± 3.1 nM). The density and affinity of benzodiazepine agonist binding sites labelled by [3H]diazepam were unchanged, but there was an increase in GABA-stimulated benzodiazepine binding. The affinity for t-[3H]butylbicyclo-o-benzoate, a ligand that binds to the GABA-activated chloride channel, was significantly increased in ICM brain membranes (KD= 148 ± 14 nM) compared with controls (KD= 245 ± 33 nM). Muscimol-stimulated 36Cl- uptake was 12% greater in microsacs prepared from ICM calf cerebral cortex, and the uptake was more sensitive to block by the GABA antagonist picrotoxin. The results show that the characteristics of the GABA receptor complex in ICM calf cortex differ from those in cortex from unaffected calves, a difference that is particularly apparent for the low-affinity, physiologically relevant GABA receptors. Study of the GABA receptor complex in ICM calves may provide a greater insight into the interactions of the various binding sites on the GABA-benzodiazepine receptor protein molecule.

Notes: Abstract: Cerebral cortex tissue was obtained at autopsy from neonatal Poll Hereford calves with clinically confirmed maple syrup urine disease (MSUD), neonatal Holstein-Friesian calves with clinically confirmed citrullinemia, and matched controls. From this, synaptosomes were prepared for studies of neurotransmitter amino acid uptake and stimulus-induced release, and synaptic plasma membranes were obtained for studies of associated postsynaptic receptor binding sites. As well as having abnormal brain tissue concentrations of the pathognomic plasma amino acids (markedly increased levels of the branched-chain compounds valine, isoleucine, and leucine in MSUD; marked elevation of citrulline levels in citrullinemia), both groups of diseased animals showed reduced, brain tissue concentrations of each of the transmitter amino acids glutamate, aspartate, and γ-aminobutyric acid (GABA). Nontransmitter amino acids were generally unaffected in either disease. Citrullinemic calves showed a marked increase in brain glutamine concentration; in calves with MSUD, the glutamine concentration was raised, but to a much lesser extent. The Na+-dependent synaptosomal uptake of both glutamate and GABA was markedly reduced (to 〈50% of control values in both cases) in citrullinemic calves but was unaltered in calves with MSUD. Whereas synaptosomes from normal calves showed the expected stimulus-coupled release of transmitter amino acids, especially glutamate and aspartate, and no response to stimulus of nontransmitter amino acids, there was no increased release of transmitter amino acids in response to depolarization in synaptosomes from citrullinemic calves. This was in part because the extracellular concentrations of these compounds in citrullinemic control incubations were already high, especially for glutamate—basal extrasynaptosomal glutamate concentrations were some 20-fold higher than those found with synaptosomes from normal calves—so that further stimuluscoupled enhancement was not possible. Calves with MSUD showed a marked loss in number of postsynaptic GABAA receptors (to ∼-50% of normal values), as assessed from [3H]diazepam binding studies. In contrast, there was no loss of this receptor site in citrullinemic calves. Calves with citrullinemia showed a marked reduction in the affinity and density of postsynaptic glutamate N-methyl-D-aspartate receptors as assessed from [3H]MK-801 binding studies. In contrast, calves with MSUD showed no change in this parameter. These studies show that two major recessively inherited diseases of cattle have similar, but distinct, neurochemical pathologies. The MSUD encephalopathy appears to be driven by a diminution of GABA-mediated inhibitory neurotransmission, whereas in citrullinemia the equivalent proconvulsive state may be driven by a relative increase in glutamate-mediated excitatory activity.

Notes: Abstract: The expression and distribution of mRNA encoding pre-proatrial natriuretic peptide (ppANP) in rat brain has been investigated by in situ hybridization of two 35S-labeled synthetic DNA Oligonucleotides, based on a cDNA clone sequence that encodes rat ppANP. The highest relative concentrations of ppANP mRNA were detected in the medial preoptic hypothalamic nucleus (“anteroventral/third ventricle region”) and the medial habenula. Moderate concentrations of ppANP mRNA were observed in the CAl pyramidal cells of the hippocampus, the endopiriform nucleus, the arcuate nucleus, the zona incerta. and cells of the pontine tegmental and peduculopontine nuclei. Several of these regions, including the habenula and the hypothalamic areas, have previously been reported to contain atrial natriuretic peptide (ANP)-like immunoreactivity, but the expression of ppANP mRNA in CAl pyramidal cells suggests the occurrence of differential translation of ppANP mRNA into protein product in different brain regions, or the existence of different immunological forms of the peptide. The abundance of ppANP mRNA in brain was relatively low in comparison with that previously reported for many other mRNA species encoding other brain neuropeptides. These results demonstrate that ANP gene expression occurs in discrete neuronal populations of the CNS and that studies of the regulation of this expression should now be possible using quantitative in situ hybridization.

Notes: Relaxin is a peptide hormone with known actions associated with female reproductive physiology, but it has also been identified in the brain. Only one relaxin gene had been characterized in rodents until recently when a novel human relaxin gene, human gene-3 (H3) and its mouse equivalent (M3) were identified. The current study reports the identification of a rat homologue, rat gene-3 (R3) relaxin that is highly expressed in a discrete region of the adult brain. The full R3 relaxin cDNA was generated using RT-PCR and 3′ and 5′ RACE protocols. The derived amino acid sequence of R3 relaxin retains all the characteristic features of a relaxin peptide and has a high degree of homology with H3 and M3 relaxin. The distribution of R3 relaxin mRNA in adult rat brain was determined and highly abundant expression was only detected in neurons of the ventromedial dorsal tegmental nucleus (vmDTg) in the pons, whereas all other brain areas were unlabelled or contained much lower mRNA levels. Relaxin binding sites and relaxin immunoreactivity were also detected in the vmDTg. These together with earlier findings provide strong evidence for a role(s) for multiple relaxin peptides as neurotransmitters and/or modulators in the rat CNS.

Notes: Abstract: Galanin has been ascribed several physiological roles that are thought to be mediated via multiple galanin receptors. Recently, two galanin receptors—galanin receptor-1 (GalR1) and galanin receptor-2 (GalR2)—have been cloned and characterized and shown to have differences in amino acid sequence, pharmacology, and second messenger signaling systems. Previous studies have demonstrated an up-regulation of galanin expression in damaged neurons of several different types. Using in situ hybridization histochemistry this study investigated whether adult cranial motor neurons express mRNAs encoding GalR1 and/or GalR2 and explored possible time-dependent changes in these transcripts following facial nerve injury. GalR2 mRNA levels were increased in the ipsilateral facial nucleus 3 (∼1.8-fold) and 7 days (∼3.7-fold) after unilateral facial nerve crush and had returned to levels equivalent to those in contralateral controls by 14–21 days. GalR1 mRNA was not detected in facial nuclei of naive, sham-operated, or operated rats but was present in adjacent reticular nuclei. Galanin mRNA levels were also increased eight- to 10-fold in the ipsilateral facial nucleus following nerve injury. These experiments confirm the putative importance of galanin signaling systems after nerve injury by demonstating a differential response of galanin receptor subtypes and suggest an important “autoreceptor” role for the GalR2 receptor in these processes.

Notes: Abstract: The binding of [3H]spiperone, a neuroleptic/dopamine receptor ligand, to membranes of the ventral tegmental area of the rat was studied in vitro and found to be rapid, saturable, reversible, and of high affinity. Specific binding was displaced by the dopaminergic agonists dopamine, apomorphine, and 2-amino-6,7-dihydroxytetralin, and stereospecifically by the neuroleptic drugs butaclamol and flupenthixol. Bromocryptine and other ergots displaced the binding, as did the D-2 antagonists domperidone, molindone, metoclopramide, and sulpiride. Noradrenergic, histaminergic, and serotonergic components of the binding were not detected in displacement studies with various agonists and antagonists. These data are consistent with the hypothesis that [3H]spiperone labels dopamine receptors in the ventral tegmental area that are not linked to adenylate cyclase and are therefore likely to be of the D-2 type.

Notes: Abstract: The rat ventral tegmentum (containing somata and dendrites of mesolimbic dopaminergic neurones) contained 1.3 μmnol/g wet weight of glycine. Slices of ventral tegmentum accumulated exogenous [3H]glycine by an energy-, temperature- and sodium-dependent mechanism. The uptake was mediated by two different transport systems; one system with relatively low affinity for glycine (Km∼400 μm) and the other a higher affinity for glycine (Km∼ 10 μm). Small amino acid analogues of glycine inhibited the uptake process, the most potent being taurine and β-alanine (47% and 44% inhibition, respectively, at 1 mm). Release of exogenous [3H]glycine by elevated potassium and by protoveratrine A was calcium-dependent and tetrodotoxin-sensitive. Glycine (500 μm-2 mm) potentiated the protoveratrine A-induced release of exogenous [3H]dopamine from slices of ventral tegmentum; this potentiation was blocked by strychnine (10 μm). A convulsant dose of strychnine elevated the concentration of 3,4-dihydroxyphenylacetic acid in the ventral tegmentum. Glycine is likely to be a transmitter in the ventral tegmentum and to have a role regulating the activity of somatodendritic regions of mesolimbic dopaminergic neurones.