Nitric Oxide–Soluble Guanylyl Cyclase–Cyclic GMP Signaling in the Striatum: New Targets for the Treatment of Parkinson's Disease?

Striatal nitric oxide (NO)-producing interneurons play an important role in the regulation of corticostriatal synaptic transmission and motor behavior. Striatal NO synthesis is driven by concurrent activation of NMDA and dopamine (DA) D1 receptors. NO diffuses into the dendrites of medium-sized spiny neurons which contain high levels of NO receptors called soluble guanylyl cyclases (sGC). NO-mediated activation of sGC leads to the synthesis of the second messenger cGMP. In the intact striatum, transient elevations in intracellular cGMP primarily act to increase neuronal excitability and to facilitate glutamatergic corticostriatal transmission. NO–cGMP signaling also functionally opposes the inhibitory effects of DA D2 receptor activation on corticostriatal transmission. Not surprisingly, abnormal striatal NO–sGC–cGMP signaling becomes apparent following striatal DA depletion, an alteration thought to contribute to pathophysiological changes observed in basal ganglia circuits in Parkinson's disease (PD). Here, we discuss recent developments in the field which have shed light on the role of NO–sGC–cGMP signaling pathways in basal ganglia dysfunction and motor symptoms associated with PD and l-DOPA-induced dyskinesias

Impedance characterization of calcia-stabilized zirconia as a function of applied field

Cubic stabilised-zirconias are well-known oxide ion conductors. They are used as solid electrolytes in oxygen sensors and in solid oxide fuel cells (SOFCs). However, it has been demonstrated recently that electronic conduction can be introduced into yttria-stabilised zirconia (YSZ), under the application of either (i) a small dc bias or (ii) for YSZ compositions with higher yttria content, by an increase in oxygen partial pressure (pO2) [1]. Such electronic conduction will have implications for materials that are to be used as ionically-conducting but electrically-insulating components in fuel cells and sensors. Please click Additional Files below to see the full abstract

Enhanced ionic conductivity of 8 mol% yttria stabilized zirconia by flash sintering

The high conductivity of O2- ions in YSZ has led to its selection as the preferred electrolyte in many solid oxide fuel cell and oxygen sensor applications[1] because of its good chemical and structural stability under the temperature and environmental conditions in operational fuel cells[2]. The addition of yttria to zirconia increases the concentration of oxygen ion vacancies, as the principal mechanism of charge compensation on replacement of Zr4+by Y3+ leads toenhanced ionic transport in the electrolyte. The highest conductivity is obtained in the cubic phase of zirconia containing 8-10 mol% Y2O3. There is much current interest in flash sintering as a novel, rapid sintering method which has evolved from initial studies on YSZ[3]. It was reported[4] that partially-stabilized, tetragonal YSZ ceramics of composition 3 mol% Y2O3, prepared by both conventional sintering and field-assisted flash sintering, developed similar microstructures. Impedance measurements showed the presence of grain and grain boundary components and at a given temperature of 300 °C, the conductivities of flash-sintered samples were 2 to 3 times higher than those of conventionally-sintered samples. This increase appeared to be not due to microstructural effects or changes; it was presumed, but not confirmed, that the conductivity increase was ionic. It has been suggested that flash sintering generates defect concentrations far above equilibrium values[5], some of which may be retained after flash. The increased conductivities were attributed to increased carrier (oxygen vacancy) concentration, although the mechanism by which these extra carriers were created was unclear. Experimental measurements of residual lattice expansion after flash were attributed to the creation of a high concentration of oxygen Frenkel defects during flash; first principles calculations showed that oxygen-related defects may be produced in much higher concentration than Zr-related defects[6]. In the present work, the ionic conductivity of flash-sintered, polycrystalline 8 mol% yttria stabilized zirconia (8YSZ) is investigated. Flash sintering was carried out at a furnace temperature of 850 °C with an electric field of 100 V cm–1 to initiate flash, the current density limit was varied between 60 and 100 mA mm–2. Post-flash impedance spectroscopy measurements over the range 215–900 °C showed that both bulk and grain boundary conductivities had increased with the increased current density limit which was set prior to flash. The conductivity increases post-flash were ionic, not electronic, although electronic conductivity probably occurred, in addition to ionic conductivity, during flash and were not attributable to sample densification or microstructural changes. The higher ionic conductivities are attributed to a change in YSZ defect structure that led to an increased concentration of mobile charge carriers. [1] N.Q. Minh, Ceramic Fuel Cells, J. Am. Ceram. Soc. 76 (1993) 563–588. [2] B. Butz, R. Schneider, D. Gerthsen, M. Schowalter, A. Rosenauer, Decomposition of 8.5 mol.% Y2O3-doped zirconia and its contribution to the degradation of ionic conductivity, Acta Mater. 57 (2009) 5480–5490. [3] M. Cologna, A.L.G. Prette, R. Raj, Flash-Sintering of Cubic Yttria-Stabilized Zirconia at 750°C for Possible Use in SOFC Manufacturing, J. Am. Ceram. Soc. 94 (2011) 316–319. [4] J.C. M’Peko, J.S.C. Francis, R. Raj, Impedance spectroscopy and dielectric properties of flash versus conventionally sintered yttria-doped zirconia electroceramics viewed at the microstructural level, J. Am. Ceram. Soc. 96 (2013). [5] R. Raj, M. Cologna, J.S.C. Francis, Influence of externally imposed and internally generated electrical fields on grain growth, diffusional creep, sintering and related phenomena in ceramics, J. Am. Ceram. Soc. 94 (2011) 1941–1965. [6] J.M. Lebrun, C.S. Hellberg, S.K. Jha, W.M. Kriven, A. Steveson, K.C. Seymour, N. Bernstein, S.C. Erwin, R. Raj, In-situ measurements of lattice expansion related to defect generation during flash sintering, J. Am. Ceram. Soc. 100 (2017) 4965–4970. * Current address: Institute of Energy Technologies, Department of Chemical Engineering, Universitat Politècnica de Catalunya, Barcelona 08019, Spai

Interactions between Procedural Learning and Cocaine Exposure Alter Spontaneous and Cortically Evoked Spike Activity in the Dorsal Striatum

We have previously shown that cocaine enhances gene regulation in the sensorimotor striatum associated with procedural learning in a running-wheel paradigm. Here we assessed whether cocaine produces enduring modifications of learning-related changes in striatal neuron activity, using single-unit recordings in anesthetized rats 1 day after the wheel training. Spontaneous and cortically evoked spike activity was compared between groups treated with cocaine or vehicle immediately prior to the running-wheel training or placement in a locked wheel (control conditions). We found that wheel training in vehicle-treated rats increased the average firing rate of spontaneously active neurons without changing the relative proportion of active to quiescent cells. In contrast, in rats trained under the influence of cocaine, the proportion of spontaneously firing to quiescent cells was significantly greater than in vehicle-treated, trained rats. However, this effect was associated with a lower average firing rate in these spontaneously active cells, suggesting that training under the influence of cocaine recruited additional low-firing cells. Measures of cortically evoked activity revealed a second interaction between cocaine treatment and wheel training, namely, a cocaine-induced decrease in spike onset latency in control rats (locked wheel). This facilitatory effect of cocaine was abolished when rats trained in the running wheel during cocaine action. These findings highlight important interactions between cocaine and procedural learning, which act to modify population firing activity and the responsiveness of striatal neurons to excitatory inputs. Moreover, these effects were found 24 h after the training and last drug exposure indicating that cocaine exposure during the learning phase triggers long-lasting changes in synaptic plasticity in the dorsal striatum. Such changes may contribute to the transition from recreational to habitual or compulsive drug taking behavior

Enhanced conductivity and nonlinear voltage–current characteristics of nonstoichiometric BaTiO3 ceramics

The electrical conductivity of both BaO-deficient and TiO2-deficient BaTiO3 ceramics shows nonohmic, low-field characteristics at temperatures >∼200°C in contrast to stoichiometric BaTiO3 for which the electrical conductivity is independent of applied voltage. The nonlinearity is observed in both bulk and grain-boundary resistances of ceramics that are both porous (∼82%) and nonporous (∼98%) and is not associated with interfacial phenomena such as Schottky barriers and memristors or with charge injection from the electrodes. Results, shown as a function of time over the temperature range 200°–750°C with field gradients in the range ∼0.5–20 V/mm, indicate that an excited state is reached that is time, temperature, and field dependent. This effect appears to be caused by departures from local electroneutrality in the defect structure of nonstoichiometric BaTiO3 which are reduced by electron transfer on application of a dc bias, leading to a more conducting, low-level excited state in which holes associated with underbonded oxygens, presumably as O− ions, are the principal charge carriers. Ceramics gradually return to their ground state in two stages on removal of the dc bias and the conductivity decreases overall by two to three orders of magnitude

Field-enhanced bulk conductivity and resistive-switching in Ca-doped BiFeO3 ceramics

The bulk conductivity at room temperature of Ca-doped BiFeO3 ceramics is p-type and increases reversibly by up to 3 orders of magnitude under the influence of a small dc bias voltage in the range B3 to 20 V mm1 . The effect occurs in both grain and grain boundary regions, is isotropic and does not involve creation of filamentary conduction pathways. It is proposed that, by means of capacitive charging and internal ionisation processes under the action of a dc bias, hole creation leads to a more conductive excited state. This gradually returns to the ground state when the dc bias is removed and the holes recombine with electrons trapped at the sample surface. The holes are believed to be created on oxygen, as O ions

Phase transition hysteresis and anomalous Curie-Weis behavior of ferroelectric tetragonaltungsten bronzes Ba2RETi2Nb3O15:RE=Nd, Sm

The ferroelectric tetragonal tungsten bronze TTB phases, Ba2RETi2Nb3O15 :RE=Nd,Sm, were prepared by low temperature solvothermal synthesis. The permittivity versus temperature data of sintered ceramics show two unusual features: first, a hysteresis of 50–100 °C between values of the Curie temperature Tc on heat-cool cycles and second: a huge depression in the Curie–Weiss temperature T0. Both effects are attributed to the complex nature of their TTB-related crystal structures with different superstructures above and below Tc and the difficulty in nucleating ferroelectric domains on cooling through Tc. Several factors may contribute to the latter difficulty: first, the structures contain two sets of crystallographic sites for the “active” Ti, Nb ions; second, the distribution of Ti and Nb over these two sets of sites is not random but partially ordered; and third, below Tc a weak commensurate superstructure perpendicular to the polar c axis is present, but above Tc a weak incommensurate superstructure in a similar orientation is present. Hence the formation of the ferroelectric structure on cooling requires both nucleation of polar domains involving two sets of cation sites and structural change from an incommensurate to a commensurate supercel

Non-Ohmic Phenomena in Mn-doped BaTiO3

We report here a novel effect in which the resistance of a semiconducting oxide ceramic increases on application of a small dc bias. The ceramic conducts at high temperatures by an n-type hopping mechanism. On application of a dc bias, conduction electrons are trapped at surface states and the resistance increases. On removal of the dc bias, the trapped electrons are released and the sample regains its original state. This effect is the mirror image of that seen with similar ceramics that conduct by a p-type mechanism whose resistance decreases reversibly on application of a small dc bias. These two phenomena together offer the possibility of novel switching devices and memristive applications, especially if the switching times can be reduced

Synthesis and characterisation of Li11RE18M4O39−δ: RE = Nd or Sm; M = Al, Co or Fe

Four new phases of general formula, Li11RE18M4O39−δ: REM = NdAl, NdCo, SmCo, SmFe, have been synthesised and characterised. The NdAl phase, and probably the others, is isostructural with the NdFe analogue, but some cation disorder and partial site occupancies prevent full structural refinement of powder neutron diffraction data. The NdCo phase also forms a solid solution with variable Li content (and charge compensation by either oxygen vacancies or variable transition metal oxidation state). The NdAl phase is a modest conductor of Li+ ions whereas the other three phases are electronic conductors, attributed to mixed valence of the transition metal ions. Subsolidus phase diagrams for the systems Li2O–Nd2O3– Al2O3, ‘CoO’ have been determined and an additional new phase, LiCoNd4O8, which appears to have a K2NiF4-related superstructure, identified