Changes In Intrinsic Properties Research Articles

Immobilizing of polyethyleneimine on bamboo viscose fiber using epichlorohydrin crosslinker for enhancing adsorption ability with lac dye

AbstractImmobilization of polyethyleneimine (PEI) on bamboo viscose fiber using epichlorohydrin (ECH) crosslinker (ABF‐e‐PEI) was employed to enhance the ability of dyeing with lac. The results from morphological observation, thermal degradation behavior, Fourier transform infrared (FTIR) analysis, x‐ray photoelectron spectroscopy (XPS) and x‐ray diffraction (XRD) clearly revealed the success of PEI‐immobilizing on fiber surface with no significant change in intrinsic properties of the fiber after modification. The modified fiber exhibited fast and efficient adsorption with the adsorption capacity >90 mg/g which was much higher than that of the unmodified adsorbent (did not exceed 10 mg/g). The results from kinetic and isotherm studies showed that the adsorption process conformed to the pseudo‐second‐order, intra‐particle diffusion and Langmuir models. Adsorption temperatures have less effect to the adsorption performance of the modified adsorbent. Electrostatic ion‐dipole interaction between protonated amines of PEI and negative charged sites of lac dye was the main proposed mechanism. Good resistance of color changes for ABF‐e‐PEI was confirmed by the color‐fastness assessment (grade 4–5), suggesting efficient method of PEI‐immobilizing using ECH crosslinker. The binding reaction of between amine groups of PEI and hydroxyl groups of the cellulosic fiber using ECH crosslinker can be expected to have a broad potential application in dyeing processes or pollution treatments due to its simple, cost‐effective, flexible and efficient method.

Modeling Synaptic Integration of Bursty and β Oscillatory Inputs in Ventromedial Motor Thalamic Neurons in Normal and Parkinsonian States.

The ventromedial motor thalamus (VM) is implicated in multiple motor functions and occupies a central position in the cortico-basal ganglia-thalamocortical loop. It integrates glutamatergic inputs from motor cortex (MC) and motor-related subcortical areas, and it is a major recipient of inhibition from basal ganglia. Previous in vitro experiments performed in mice showed that dopamine depletion enhances the excitability of thalamocortical (TC) neurons in VM due to reduced M-type potassium currents. To understand how these excitability changes impact synaptic integration in vivo, we constructed biophysically detailed mouse VM TC model neurons fit to normal and dopamine-depleted conditions, using the NEURON simulator. These models allowed us to assess the influence of excitability changes with dopamine depletion on the integration of synaptic inputs expected in vivo We found that VM neuron models in the dopamine-depleted state showed increased firing rates with the same synaptic inputs. Synchronous bursting in inhibitory input from the substantia nigra pars reticulata (SNR), as observed in parkinsonian conditions, evoked a postinhibitory firing rate increase with a longer duration in dopamine-depleted than control conditions, due to different M-type potassium channel densities. With β oscillations in the inhibitory inputs from SNR and the excitatory inputs from cortex, we observed spike-phase locking in the activity of the models in normal and dopamine-depleted states, which relayed and amplified the oscillations of the inputs, suggesting that the increased β oscillations observed in VM of parkinsonian animals are predominantly a consequence of changes in the presynaptic activity rather than changes in intrinsic properties.

Influence of a transmission oil degradation on physico-chemical properties and tribological performance

Lubricant degradation can have a significant impact on the efficiency and reliability of mechanical systems. This study analyses the effects of field operation on the physicochemical properties and tribological performances of gear transmission oils. Viscosity and composition of fresh-new oils and field-collected ones are analysed and tribological tests on the High Frequency Reciprocating Rig (HFRR) and the Mini Traction Machine (MTM) are carried out, to identify potential differences. Results reveal changes in intrinsic properties and tribological behaviour. They show that the evolution of the oil is highly dependent on the system and operating conditions, results that differ from those traditionally observed with engine oils.

A Role for KCNQ Channels on Cell Type-Specific Plasticity in Mouse Auditory Cortex after Peripheral Damage.

Damage to sensory organs triggers compensatory plasticity mechanisms in sensory cortices. These plasticity mechanisms result in restored cortical responses, despite reduced peripheral input, and contribute to the remarkable recovery of perceptual detection thresholds to sensory stimuli. Overall, peripheral damage is associated with a reduction of cortical GABAergic inhibition; however, less is known about changes in intrinsic properties and the underlying biophysical mechanisms. To study these mechanisms, we used a model of noise-induced peripheral damage in male and female mice. We uncovered a rapid, cell type-specific reduction in the intrinsic excitability of parvalbumin-expressing neurons (PVs) in layer (L) 2/3 of auditory cortex. No changes in the intrinsic excitability of either L2/3 somatostatin-expressing or L2/3 principal neurons (PNs) were observed. The decrease in L2/3 PV excitability was observed 1, but not 7, d after noise exposure, and was evidenced by a hyperpolarization of the resting membrane potential, depolarization of the action potential threshold, and reduction in firing frequency in response to depolarizing current. To uncover the underlying biophysical mechanisms, we recorded potassium currents. We found an increase in KCNQ potassium channel activity in L2/3 PVs of auditory cortex 1 d after noise exposure, associated with a hyperpolarizing shift in the minimal voltage activation of KCNQ channels. This increase contributes to the decreased intrinsic excitability of PVs. Our results highlight cell-type- and channel-specific mechanisms of plasticity after noise-induced hearing loss and will aid in understanding the pathologic processes involved in hearing loss and hearing loss-related disorders, such as tinnitus and hyperacusis.SIGNIFICANCE STATEMENT Noise-induced damage to the peripheral auditory system triggers central plasticity that compensates for the reduced peripheral input. The mechanisms of this plasticity are not fully understood. In the auditory cortex, this plasticity likely contributes to the recovery of sound-evoked responses and perceptual hearing thresholds. Importantly, other functional aspects of hearing do not recover, and peripheral damage may also lead to maladaptive plasticity-related disorders, such as tinnitus and hyperacusis. Here, after noise-induced peripheral damage, we highlight a rapid, transient, and cell type-specific reduction in the excitability of layer 2/3 parvalbumin-expressing neurons, which is due, at least in part, to increased KCNQ potassium channel activity. These studies may highlight novel strategies for enhancing perceptual recovery after hearing loss and mitigating hyperacusis and tinnitus.

Motor training promotes both synaptic and intrinsic plasticity of layer V pyramidal neurons in the primary motor cortex.

Here we examined motor training-induced synaptic and intrinsic plasticity of layer V pyramidal neurons in primary motor cortex. The training reduced presynaptic GABA release in early phase, but strengthened AMPA receptor-mediated excitatory synapses in later phase: acquired motor performance after training correlated with the strength of excitatory synapses rather than inhibitory synapses. As to the intrinsic property, the training transiently decreased firing rate in early phase, but returned to pre-training levels in later phase. Western-blot analysis detected decreased phosphorylation of Ser408-409 in GABAA receptor β3 subunits in acute phase, and increased phosphorylation of Ser831 in AMPA receptor GluA1 subunits in later phase. Live-imaging analysis of Thy1-YFP transgenic mice showed rapid and long-term spine plasticity in M1 layer V neurons, suggesting training-induced increases in self-entropy per spine. Layer V neurons in primary motor cortex (M1) are important for motor skill learning. Since pretreatment of either CNQX or APV in rats M1 layer V impaired rotor rod learning, we analyzed training-induced synaptic plasticity by whole-cell patch-clamp technique in acute brain slices. One-day trained rats showed a decrease in small inhibitory postsynaptic current (mIPSC) frequency and an increase in the paired-pulse ratio of evoked IPSCs, suggesting a transient decrease in presynaptic GABA release in early phase. Two-days trained rats showed an increase in miniature excitatory postsynaptic current (mEPSC) amplitudes/frequency and elevated AMPA/NMDA ratios, suggesting a long-term strengthening of AMPA receptor-mediated excitatory synapses. Importantly, rotor rod performance in trained rats was correlated with the mean mEPSC amplitude and the frequency obtained from that animal. In current-clamp analysis, 1-day-trained rats transiently decreased current-induced firing rate, while 2-day-trained rats returned to pre-training levels, suggesting a dynamic changes in intrinsic properties. Furthermore, western-blot analysis of layer V detected decreased phosphorylation of Ser408-409 in GABAA receptor β3 subunits in 1-day trained rats, and increased phosphorylation of Ser831 in AMPA receptor GluA1 subunits in 2-days trained rats. Finally, live-imaging analysis of Thy1-YFP transgenic mice showed that the training rapidly recruited a substantial number of spines for long-term plasticity in M1 layer V neurons. Taken together, these results indicate that motor training induces complex and diverse plasticity in M1 layer V pyramidal neurons. Abstract figure legend Schematic of motor training and rapid spine dynamics in M1 layer V neurons. Exercise training promotes physiological and morphological spine diversity. Red: glutamate and AMPA receptors. Blue: GABA and GABAA receptors. This article is protected by copyright. All rights reserved.

Cell‐type Specific Effects of AD Mutations on Hippocampal Intrinsic Firing Properties in Genetically Diverse Mice

AbstractBackgroundCognitive resilience to Alzheimer’s disease (AD) is a phenomenon whereby individuals with known AD mutations or high levels of pathology exhibit better than predicted cognitive performance. Identification of the factors governing resilience may lead to novel therapeutic interventions to treat AD. Analysis of hippocampal transcriptional profiles from susceptible and resilient AD‐BXD strains indicates that transcriptomic changes in excitatory neurons in CA1 and dentate gyrus (DG) are associated with resilience and we now seek to examine physiological changes.MethodWe adapted the Patch‐Seq method (Cadwell et al., 2017) to investigate cell type‐specific transcriptional and electrophysiological changes associated with AD using the AD‐BXD genetic reference panel (Neuner et al., 2019). Whole‐cell patch clamp was used to evaluate intrinsic excitability of neurons within the DG and CA1 of 14m old mice with cognitive deficits compared to age matched controls; their cellular contents, including the nucleus, were collected after each recording to characterize the transcriptome.ResultComparison of the intrinsic properties of DG and CA1 neurons of hippocampal slices from 5XFAD mice and their non‐transgenic (Ntg) counterparts revealed that DG granule cells from 5XFAD mice have a lower input resistance and an increased sag ratio in response to hyperpolarizing current injections. Pyramidal neurons from the CA1 of 5xFAD mice exhibit significantly more depolarized action potential thresholds, a significant increase in the medium afterhyperpolarization (mAHP) and sag ratio compared to Ntg controls. While these intrinsic properties are proxy measures for neuronal excitability, we did not observe a significant effect of genotype on firing rate in response to 1s and 15s depolarizing current steps.ConclusionOur findings newly demonstrate disease related changes to intrinsic firing properties of DG granule cells at 14mo indicating that these neurons may be hypoexcitable. Also found, CA1 neurons from AD mice exhibit an increased mAHP and changes to sag ratio and AP threshold, indicating they too become less excitable. Future work will add additional AD‐BXD strains characterized as resilient or susceptible to the AD transgene to discover changes in intrinsic properties that could underlie resilience. We will also use an integrated analysis of transcriptomic and electrophysiological data to identify relevant functional targets for validation.

Synaptic determinants of cholinergic interneurons hyperactivity during parkinsonism

Parkinson’s disease is a neurodegenerative ailment generated by the loss of dopamine in the basal ganglia, mainly in the striatum. The disease courses with increased striatal levels of acetylcholine, disrupting the balance among these modulatory transmitters. These modifications disturb the excitatory and inhibitory balance in the striatal circuitry, as reflected in the activity of projection striatal neurons. In addition, changes in the firing pattern of striatal tonically active interneurons during the disease, including cholinergic interneurons (CINs), are being searched. Dopamine-depleted striatal circuits exhibit pathological hyperactivity as compared to controls. One aim of this study was to show how striatal CINs contribute to this hyperactivity. A second aim was to show the contribution of extrinsic synaptic inputs to striatal CINs hyperactivity. Electrophysiological and calcium imaging recordings in Cre-mice allowed us to evaluate the activity of dozens of identified CINs with single-cell resolution in ex vivo brain slices. CINs show hyperactivity with bursts and silences in the dopamine-depleted striatum. We confirmed that the intrinsic differences between the activity of control and dopamine-depleted CINs are one source of their hyperactivity. We also show that a great part of this hyperactivity and firing pattern change is a product of extrinsic synaptic inputs, targeting CINs. Both glutamatergic and GABAergic inputs are essential to sustain hyperactivity. In addition, cholinergic transmission through nicotinic receptors also participates, suggesting that the joint activity of CINs drives the phenomenon; since striatal CINs express nicotinic receptors, not expressed in striatal projection neurons. Therefore, CINs hyperactivity is the result of changes in intrinsic properties and excitatory and inhibitory inputs, in addition to the modification of local circuitry due to cholinergic nicotinic transmission. We conclude that CINs are the main drivers of the pathological hyperactivity present in the striatum that is depleted of dopamine, and this is, in part, a result of extrinsic synaptic inputs. These results show that CINs may be a main therapeutic target to treat Parkinson’s disease by intervening in their synaptic inputs.

Investigation of Neural Substrates of Erroneous Behavior in a Delayed-Response Task.

Motor cortical neurons exhibit persistent selective activities (selectivity) during motor planning. Experimental perturbation of selectivity results in the failure of short-term memory retention and consequent behavioral biases, demonstrating selectivity as a neural characteristic of encoding previous sensory input or future action. However, even without experimental manipulation, animals occasionally fail to maintain short-term memory leading to erroneous choice. Here, we investigated neural substrates that lead to the incorrect formation of selectivity during short-term memory. We analyzed neuronal activities in anterior lateral motor cortex (ALM) of mice, a region known to be engaged in motor planning while mice performed the tactile delayed-response task. We found that highly selective neurons lost their selectivity while originally nonselective neurons showed selectivity during the error trials where mice licked toward incorrect direction. We assumed that those alternations would reflect changes in intrinsic properties of population activity. Thus, we estimated an intrinsic manifold shared by neuronal population (shared space), using factor analysis (FA) and measured the association of individual neurons with the shared space by communality, the variance of neuronal activity accounted for by the shared space. We found a positive correlation between selectivity and communality over ALM neurons, which disappeared in erroneous behavior. Notably, neurons showing selectivity alternations between correct and incorrect licking also underwent proportional changes in communality. Our results demonstrated that the extent to which an ALM neuron is associated with the intrinsic manifolds of population activity may elucidate its selectivity and that disruption of this association may alter selectivity, likely leading to erroneous behavior.

Iron-iron oxide supported palladium catalyst for the interconversion of formate and carbon dioxide

Synthesized palladium-coated iron-iron oxide (Fe@FeOx/Pd) nanoparticles (NPs) using the successive salt reduction method are tested for their activity and stability toward formate oxidation (FO) and electrochemical CO2 reduction to formate (eCO2RF). The experimental results for FO show a current density at 0.12 V vs. Ag/AgCl of 1.65 mA/cm2 over 1 h, which is 16 times higher than that for Pd NPs. Furthermore, the same catalyst displays a higher current density with a faradaic efficiency (FE) of 95.6 % toward the eCO2RF, and exhibits a lower degree of CO adsorption. The iron-iron oxide interaction with the overlayer palladium is characterized by TEM/EDX, XPS/UPS, Mössbauer spectroscopy, and electrochemical techniques such as cyclic voltammetry (CV) and chronoamperometry (CA). NMR is used to estimate the amount of formate produced by the eCO2RF. A positive binding energy shift of the Pd 3d peak and the upshift of the d-band center as measured by XPS compared to monometallic homemade Pd NPs confirm that the electronic perturbation of the catalyst surface plays a major role in enhancing the performance of Fe@FeOx/Pd for both FO and eCO2RF. Furthermore, the work function as measured by UPS for the Fe@FeOx/Pd material is lower than that for monometallic Pd confirming a change in chemical properties of the catalyst surface. Finally, Mössbauer spectroscopy is used to determine the composition, structure and nature of all sites of the Fe@FeOx substrate before use and the perturbation of their intrinsic properties by the Pd overlayer. This change in intrinsic properties of the Pd coated material provides additional explanations for the electrochemical improvement measured for this catalyst toward both FO and eCO2RF

The effect of calcination temperature on the electrocatalytic activity of Ni–Co–Ir-oxide and Ni–Co–Ru-oxide anodes in the oxygen evolution reaction in alkaline medium

The influence of calcination temperature on the electrocatalytic properties of thermally-prepared (Ni0.4Co0.6)0.90Ir0.10-oxide and (Ni0.4Co0.6)0.90Ru0.10-oxide in the oxygen evolution reaction (OER) was investigated in an alkaline medium. It was shown that by lowering the calcination temperature, the OER activity of the two materials increased significantly, yielding a maximum at 300 °C. The increase in electrocatalytic activity of the oxides was related to the change in intrinsic properties of the anodes, predominantly to the modification of the electronic structure and to the increase in hydroxide content. The (Ni0.4Co0.6)0.90Ir0.10-oxide was found to significantly outperform the current state-of-the-art OER electrocatalyst, pure Ir-oxide, while the electrocatalytic activity of (Ni0.4Co0.6)0.90Ru0.10-oxide was measured to be much higher than that of the Ni0.4Co0.6-oxide base, thus demonstrating the synergistic action of Ni/Co/Ir and Ni/Co/Ru in their oxides.

Post-stroke epileptogenesis is associated with altered intrinsic properties of hippocampal pyramidal neurons leading to increased theta resonance

Brain insults like stroke, trauma or infections often lead to blood-brain barrier-dysfunction (BBBd) frequently resulting into epileptogenesis. Affected patients suffer from seizures and cognitive comorbidities that are potentially linked to altered network oscillations. It has been shown that a hippocampal BBBd in rats leads to in vivo seizures and increased power at theta (3–8 Hz), an important type of network oscillations. However, the underlying cellular mechanisms remain poorly understood. At membrane potentials close to the threshold for action potentials (APs) a subpopulation of CA1 pyramidal cells (PCs) displays intrinsic resonant properties due to an interplay of the muscarine-sensitive K+-current (IM) and the persistent Na+-current (INaP). Such resonant neurons are more excitable and generate more APs when stimulated at theta frequencies, being strong candidates for contributing to hippocampal theta oscillations during epileptogenesis. We tested this hypothesis by characterizing changes in intrinsic properties of hippocampal PCs one week after post-stroke epileptogenesis, a model associated with BBBd, using slice electrophysiology and computer modeling. We find a higher proportion of resonant neurons in BBBd compared to sham animals (47 vs. 29%), accompanied by an increase in their excitability. In contrast, BBBd non-resonant neurons showed a reduced excitability, presented with lower impedance and more positive AP threshold. We identify an increase in IM combined with either a reduction in INaP or an increase in ILeak as possible mechanisms underlying the observed changes. Our results support the hypothesis that a higher proportion of more excitable resonant neurons in the hippocampus contributes to increased theta oscillations and an increased likelihood of seizures in a model of post-stroke epileptogenesis.

Changes of Aortic Tissue MicroRNA/mRNA Expression in Patients with Long-Term Left Ventricular Assist Device

Purpose Attenuation of physiological pulsatility after continuous flow left ventricular assist device (LVAD) implantation has been reported as a contributor to alteration of aortic wall morphology and function. MicroRNAs are non-coding RNAs that act to regulate translation of messenger RNA (mRNA) into proteins and are fine-tuners of gene expression in response to pathophysiological stimuli. Differences in gene expression (mRNA) and in post-transcriptional regulators (microRNAs) could reflect biological response to exposure to the low pulsatile environment. We hypothesized that pulsatility deficit caused by LVAD may influence miRNA/mRNA expression in aortic tissue. The aim of the study was to detect miRNA/mRNA associations in the aortic tissue during LVAD support. Methods Aortic samples were collected at the time of LVAD implant and at heart transplantation in 16 patients (mean age 49.6±16.8 years; 3 females) and examined for miRNA/mRNA profiling. QuantSeq 3′ mRNA-Sequencing was used to examine differences in gene expression. Using human miRNome panels a profile of 752 miRNAs was identified. Results A total of 277 mRNAs were dysregulated after LVAD support (padj Conclusion The study provides additional insight in pathophysiology of vascular changes after LVAD implantation. A significant regulation of mRNAs involved in ECM and collagen fibers organization in response to implantation of LVAD was observed, which may suggest infliction of ECM homeostasis resulting in changes of intrinsic properties of vascular wall and arterial stiffness. Downregulation of miRNAs involved in molecular processes related to immune response, could implicate dysregulation in inflammatory processes after LVAD implantation.

Intrinsic plasticity and birdsong learning

Although information processing and storage in the brain is thought to be primarily orchestrated by synaptic plasticity, other neural mechanisms such as intrinsic plasticity are available. While a number of recent studies have described the plasticity of intrinsic excitability in several types of neurons, the significance of non-synaptic mechanisms in memory and learning remains elusive. After reviewing plasticity of intrinsic excitation in relation to learning and homeostatic mechanisms, we focus on the intrinsic properties of a class of basal-ganglia projecting song system neurons in zebra finch, how these related to each bird’s unique learned song, how these properties change over development, and how they are maintained dynamically to rapidly change in response to auditory feedback perturbations. We place these results in the broader theme of learning and changes in intrinsic properties, emphasizing the computational implications of this form of plasticity, which are distinct from synaptic plasticity. The results suggest that exploring reciprocal interactions between intrinsic and network properties will be a fruitful avenue for understanding mechanisms of birdsong learning.

Experimental and first-principles study of defect-induced electronic and magnetic properties of ZnO nanocrystals

We investigate defect-induced electronic and magnetic properties of zinc oxide (ZnO) nanocrystalline powders prepared by mechanical milling. The average crystallite size decreases as the milling time is increased but the wurtzite structure is stable even after 60 hours of milling. The structural properties are characterized by X-ray diffraction and transmission electron microscopy. The chemical composition of pure unmilled and as-milled powders is determined by X-ray photoelectron spectroscopy. Raman scattering spectra were analyzed to find evidence of crystallinity and defect structures in the milled powders. The results obtained from electronic paramagnetic resonance studies demonstrate that the defects are due to both oxygen and zinc vacancies. Since defect-induced magnetism has potential application in spintronic devices, we measured the M-H loops of ZnO powders at different temperatures. We observed that there is a transition from paramagnetic to ferromagnetic behavior due to the vacancies caused by the crystallite size reduction. We also calculated the band structures and density of states within the framework of density functional theory with Hubbard U correction to understand the electronic properties of ZnO for both pure crystals and crystals with defects. A simple mechanical milling process can produce a crystallite size of approximately 10 nm after 40 hours of milling, and the resulting significant changes in electronic properties favor superior application in devices as compared with the bulk. This change of intrinsic properties in ZnO is largely due to the size effect and the increase of defect density.

Postnatal Development of Functional Projections from Parasubiculum and Presubiculum to Medial Entorhinal Cortex in the Rat.

Neurons in parasubiculum (PaS), presubiculum (PrS), and medial entorhinal cortex (MEC) code for place (grid cells) and head direction. Directional input has been shown to be important for stable grid cell properties in MEC, and PaS and PrS have been postulated to provide this information to MEC. In line with this, head direction cells in those brain areas are present at postnatal day 11 (P11), having directional tuning that stabilizes shortly after eye opening, which is before premature grid cells emerge in MEC at P16. Whether functional connectivity between these structures exists at those early postnatal stages is unclear. Using anatomical tracing, voltage-sensitive dye imaging and single-cell patch recordings in female and male rat brain slices between P2 and P61, we determined when the pathways from PaS and PrS to MEC emerge, become functional, and how they develop. Anatomical connections from PaS and PrS to superficial MEC emerge between P4 and P6. Monosynaptic connectivity from PaS and PrS to superficial MEC was measurable from P9 to P10 onward, whereas connectivity with deep MEC was measurable from P11 to P12. From P14/P15 on, reactivity of MEC neurons to parasubicular and presubicular inputs becomes adult-like and continues to develop until P28-P30. The maturation of the efficacy of both inputs between P9 and P21 is paralleled by maturation of morphological properties, changes in intrinsic properties of MEC principal neurons, and changes in the GABAergic network of MEC. In conclusion, synaptic projections from PaS and PrS to MEC become functional and adult-like before the emergence of grid cells in MEC.SIGNIFICANCE STATEMENT Head direction information, crucial for grid cells in medial entorhinal cortex (MEC), is thought to enter MEC via parasubiculum (PaS) and presubiculum (PrS). Unraveling the development of functional connections between PaS, PrS, and MEC is key to understanding how spatial navigation, an important cognitive function, may evolve. To gain insight into the development, we used anatomical tracing techniques, voltage-sensitive dye imaging, and single-cell recordings. The combined data led us to conclude that synaptic projections from PaS and PrS to MEC become functional and adult-like before eye opening, allowing crucial head direction information to influence place encoding before the emergence of grid cells in rat MEC.

Ca2+ Channels Involvement in Low-Frequency Stimulation-Mediated Suppression of Intrinsic Excitability of Hippocampal CA1 Pyramidal Cells in a Rat Amygdala Kindling Model

Low-frequency stimulation has demonstrated promising seizure suppression in animal models of epilepsy, while the mechanism of the effect is still debated. Changes in intrinsic properties have been recognized as a prominent pathophysiologically relevant feature of numerous neurological disorders including epilepsy. Here, it was evaluated whether LFS can preserve the intrinsic neuronal electrophysiological properties in a rat model of epilepsy, focusing on the possible involvement of voltage-gated Ca2+ channels. The amygdala kindling model was induced by 3 s monophasic square wave pulses (50 Hz, 1 ms duration, 12times/day at 5 min intervals). Both LFS alone and kindled plus LFS (KLFS) groups received four packages of LFS (each consisting of 200 monophasic square pulses, 0.1 ms pulse duration at 1 Hz with the after discharge threshold intensity), which in KLFS rats was applied immediately after kindling induction. Whole-cell patch-clamp recordings were made in the presence of fast synaptic blockers 24 h after the last kindling stimulations or following kindling stimulations plus LFS application. In the KLFS group, both the rebound excitation and kindling-induced intrinsic hyperexcitability were decreased, associated with a regular intrinsic firing as indicated by a lower coefficient of variation. The amplitude of afterdepolarization (ADP) and its area under the curve were both decreased in the KLFS group compared to the kindled group. LFS prevented the increasing effect of kindling on Ca2+ currents in the KLFS group. Findings provided evidence for a novel form of epileptiform activity suppression by LFS in the presence of synaptic blockade possibly by decreasing Ca2+ currents.

Surface Treatment of Carbon Fibers by Oxy-Fluorination

In this paper, the oxy-fluorination process and the influence of different concentrations of fluorine and oxygen in the gas phase on the physicochemical properties of polyacrylonitrile(PAN)-based carbon fibers are described. The properties of the treated carbon structures are determined by zeta potential and tensiometry measurements. In addition, changes in surface composition and morphology are investigated by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Adhesion properties are characterized by the single fiber pull-out (SFPO) test. Furthermore, changes in intrinsic properties are described by means of tensile and density measurements. After a primary desizing effect by oxy-fluorination, an increased number of oxygen-containing surface functional groups could be detected, which led to more debonding work in SFPOs with an epoxy-based matrix. It was also shown that the polar surface energy grows with rising fluorine concentration in the reaction gas mixture. In addition, a minor increase of ~10% in the maximum strength of PAN-based carbon fibers is detected by single fiber tensile measurements after oxy-fluorination with a fluorine content of 5% in the reaction mixture.

Changes in Functional Properties of Rat Hippocampal Neurons Following Pentylenetetrazole-induced Status Epilepticus

Pathophysiological remodeling processes following status epilepticus (SE) play a critical role in the pathophysiology of epilepsy but have not yet been not fully investigated. In the present study, we examined changes in intrinsic properties of pyramidal neurons, basal excitatory synaptic transmission, and short-term synaptic plasticity in hippocampal slices of rats after SE. Seizures were induced in 3-week-old rats by an intraperitoneal pentylenetetrazole (PTZ) injection. Only animals with generalized seizures lasting more than 30 min were included in the experiments. We found that CA1 pyramidal neurons became more excitable and started firing at a lower excitatory input due to a significant increase in input resistance. However, basal excitatory synaptic transmission was reduced in CA3-CA1 synapses, thus preventing the propagation of excitation through neural networks. A significant increase in paired-pulse facilitation 1 d after SE pointed to a decrease in the probability of glutamate release. Increased intrinsic excitability of neurons and decreased synaptic transmission differentially affected the excitability of a neural network. In terms of changes in seizure susceptibility after SE, we observed a significant increase in the maximal electroshock threshold 1 day after SE, suggesting a decrease in seizure susceptibility. However, after 1 week, there was no difference in seizure susceptibility between control and post-SE rats. The effects of SE on functional properties of hippocampal neurons were transient in the PTZ model, and most of them had recovered 1 week after SE. However, some minor alterations, such as smaller amplitude field potentials, were observed 1 month after SE.

ERG3 potassium channel-mediated suppression of neuronal intrinsic excitability and prevention of seizure generation in mice.

ERG3 channels have a high expression level in the central nervous system. Knockdown of ERG3 channels enhances neuronal intrinsic excitability (caused by decreased fast afterhyperpolarization, shortened delay time to the generation of an action potential and enhanced summation of somatic excitatory postsynaptic potentials) in hippocampal CA1 pyramidal neurons and dentate gyrus granule cells. The expression of ERG3 protein is reduced in human and mouse hippocampal epileptogenic foci. Knockdown of ERG3 channels in hippocampus enhanced seizure susceptibility, while mice treated with the ERG channel activator NS-1643 were less prone to epileptogenesis. The results provide strong evidence that ERG3 channels have a crucial role in the regulation of neuronal intrinsic excitability in hippocampal CA1 pyramidal neurons and dentate gyrus granule cells and are critically involved in the onset and development of epilepsy. The input-output relationship of neuronal networks depends heavily on the intrinsic properties of their neuronal elements. Profound changes in intrinsic properties have been observed in various physiological and pathological processes, such as learning, memory and epilepsy. However, the cellular and molecular mechanisms underlying acquired changes in intrinsic excitability are still not fully understood. Here, we demonstrate that ERG3 channels are critically involved in the regulation of intrinsic excitability in hippocampal CA1 pyramidal neurons and dentate gyrus granule cells. Knock-down of ERG3 channels significantly increases neuronal intrinsic excitability, which is mainly caused by decreased fast afterhyperpolarization, shortened delay time to the generation of an action potential and enhanced summation of somatic excitatory postsynaptic potentials. Interestingly, the expression level of ERG3 protein is significantly reduced in human and mouse brain tissues with temporal lobe epilepsy. Moreover, ERG3 channel knockdown in hippocampus significantly enhanced seizure susceptibility, while mice treated with the ERG channel activator NS-1643 were less prone to epileptogenesis. Taken together, our results suggest ERG3 channels play an important role in determining the excitability of hippocampal neurons and dysregulation of these channels may be involved in the generation of epilepsy. ERG3 channels may thus be a novel therapeutic target for the prevention of epilepsy.

Sex-differences in diastolic dysfunction in hypertrophic cardiomyopathy

Background: One of the first clinically detectable alterations in heart function in hypertrophic cardiomyopathy (HCM) is a decline in diastolic function. Diastolic dysfunction is caused by changes in intrinsic properties of cardiomyocytes and/or an increase in fibrosis. We investigated if clinical and cellular parameters of diastolic function are sex-dependent in HCM.