Preictal Activity of Subicular, CA1, and Dentate Gyrus Principal Neurons in the Dorsal Hippocampus before Spontaneous Seizures in a Rat Model of Temporal Lobe Epilepsy

PubMed Central

Fujita, Satoshi; Toyoda, Izumi; Thamattoor, Ajoy K.

2014-01-01

Previous studies suggest that spontaneous seizures in patients with temporal lobe epilepsy might be preceded by increased action potential firing of hippocampal neurons. Preictal activity is potentially important because it might provide new opportunities for predicting when a seizure is about to occur and insight into how spontaneous seizures are generated. We evaluated local field potentials and unit activity of single, putative excitatory neurons in the subiculum, CA1, CA3, and dentate gyrus of the dorsal hippocampus in epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Average action potential firing rates of neurons in the subiculum, CA1, and dentate gyrus, but not CA3, increased significantly and progressively beginning 2–4 min before locally recorded spontaneous seizures. In the subiculum, CA1, and dentate gyrus, but not CA3, 41–57% of neurons displayed increased preictal activity with significant consistency across multiple seizures. Much of the increased preictal firing of neurons in the subiculum and CA1 correlated with preictal theta activity, whereas preictal firing of neurons in the dentate gyrus was independent of theta. In addition, some CA1 and dentate gyrus neurons displayed reduced firing rates preictally. These results reveal that different hippocampal subregions exhibit differences in the extent and potential underlying mechanisms of preictal activity. The finding of robust and significantly consistent preictal activity of subicular, CA1, and dentate neurons in the dorsal hippocampus, despite the likelihood that many seizures initiated in other brain regions, suggests the existence of a broader neuronal network whose activity changes minutes before spontaneous seizures initiate. PMID:25505320

dRGT theory of massive gravity from spontaneous symmetry breaking

NASA Astrophysics Data System (ADS)

Torabian, Mahdi

2018-05-01

In this note we propose a topological action for a Poincare times diffeomorphism invariant gauge theory. We show that there is Higgs phase where the gauge symmetry is spontaneous broken to a diagonal Lorentz subgroup and gives the Einstein-Hilbert action plus the dRGT potential terms. In this vacuum, there are five (three from Goldstone modes) propagating degrees of freedom which form polarizations of a massive spin 2 particle, an extra healthy heavy scalar (Higgs) mode and no Boulware-Deser ghost mode. We further show that the action can be derived in a limit from a topological de Sitter invariant gauge theory in 4 dimensions.

Sodium and calcium currents shape action potentials in immature mouse inner hair cells

PubMed Central

Marcotti, Walter; Johnson, Stuart L; Rüsch, Alfons; Kros, Corné J

2003-01-01

Before the onset of hearing at postnatal day 12, mouse inner hair cells (IHCs) produce spontaneous and evoked action potentials. These spikes are likely to induce neurotransmitter release onto auditory nerve fibres. Since immature IHCs express both α1D (Cav1.3) Ca2+ and Na+ currents that activate near the resting potential, we examined whether these two conductances are involved in shaping the action potentials. Both had extremely rapid activation kinetics, followed by fast and complete voltage-dependent inactivation for the Na+ current, and slower, partially Ca2+-dependent inactivation for the Ca2+ current. Only the Ca2+ current is necessary for spontaneous and induced action potentials, and 29 % of cells lacked a Na+ current. The Na+ current does, however, shorten the time to reach the action-potential threshold, whereas the Ca2+ current is mainly involved, together with the K+ currents, in determining the speed and size of the spikes. Both currents increased in size up to the end of the first postnatal week. After this, the Ca2+ current reduced to about 30 % of its maximum size and persisted in mature IHCs. The Na+ current was downregulated around the onset of hearing, when the spiking is also known to disappear. Although the Na+ current was observed as early as embryonic day 16.5, its role in action-potential generation was only evident from just after birth, when the resting membrane potential became sufficiently negative to remove a sizeable fraction of the inactivation (half inactivation was at −71 mV). The size of both currents was positively correlated with the developmental change in action-potential frequency. PMID:12937295

Development of a spontaneously active dorsal root ganglia assay using multiwell multielectrode arrays

PubMed Central

Newberry, Kim; Wang, Shuya; Hoque, Nina; Kiss, Laszlo; Ahlijanian, Michael K.; Herrington, James

2016-01-01

In vitro phenotypic assays of sensory neuron activity are important tools for identifying potential analgesic compounds. These assays are typically characterized by hyperexcitable and/or abnormally, spontaneously active cells. Whereas manual electrophysiology experiments provide high-resolution biophysical data to characterize both in vitro models and potential therapeutic modalities (e.g., action potential characteristics, the role of specific ion channels, and receptors), these techniques are hampered by their low throughput. We have established a spontaneously active dorsal root ganglia (DRG) platform using multiwell multielectrode arrays (MEAs) that greatly increase the ability to evaluate the effects of multiple compounds and conditions on DRG excitability within the context of a cellular network. We show that spontaneous DRG firing can be attenuated with selective Na+ and Ca2+ channel blockers, as well as enhanced with K+ channel blockers. In addition, spontaneous activity can be augmented with both the transient receptor potential cation channel subfamily V member 1 agonist capsaicin and the peptide bradykinin and completely blocked with neurokinin receptor antagonists. Finally, we validated the use of this assay by demonstrating that commonly used neuropathic pain therapeutics suppress DRG spontaneous activity. Overall, we have optimized primary rat DRG cells on a multiwell MEA platform to generate and characterize spontaneously active cultures that have the potential to be used as an in vitro phenotypic assay to evaluate potential therapeutics in rodent models of pain. PMID:27052585

Differential calcium dependence in basal and forskolin-potentiated spontaneous transmitter release in basolateral amygdala neurons.

PubMed

Miura, Yuki; Naka, Masamitsu; Matsuki, Norio; Nomura, Hiroshi

2012-10-31

Action potential-independent transmitter release, or spontaneous release, is postulated to produce multiple postsynaptic effects (e.g., maintenance of dendritic spines and suppression of local dendritic protein synthesis). Potentiation of spontaneous release may contribute to the precise modulation of synaptic function. However, the expression mechanism underlying potentiated spontaneous release remains unclear. In this study, we investigated the involvement of extracellular and intracellular calcium in basal and potentiated spontaneous release. Miniature excitatory postsynaptic currents (mEPSCs) of the basolateral amygdala neurons in acute brain slices were recorded. Forskolin, an adenylate cyclase activator, increased mEPSC frequency, and the increase lasted at least 25 min after washout. Removal of the extracellular calcium decreased mEPSC frequency in both naïve and forskolin-treated slices. On the other hand, chelation of intracellular calcium by BAPTA-AM decreased mEPSC frequency in naïve, but not in forskolin-treated slices. A blockade of the calcium-sensing receptor (CaSR) resulted in an increase in mEPSC frequency in forskolin-treated, but not in naïve slices. These findings indicate that forskolin-induced potentiation is accompanied by changes in the mechanisms underlying Ca(2+)-dependent spontaneous release. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Enhancement by citral of glutamatergic spontaneous excitatory transmission in adult rat substantia gelatinosa neurons.

PubMed

Zhu, Lan; Fujita, Tsugumi; Jiang, Chang-Yu; Kumamoto, Eiichi

2016-02-10

Although citral, which is abundantly present in lemongrass, has various actions including antinociception, how citral affects synaptic transmission has not been examined as yet. Citral activates in heterologous cells transient receptor potential vanilloid-1, ankyrin-1, and melastatin-8 (TRPV1, TRPA1, and TRPM8, respectively) channels, the activation of which in the spinal lamina II [substantia gelatinosa (SG)] increases the spontaneous release of L-glutamate from nerve terminals. It remains to be examined what types of transient receptor potential channel in native neurons are activated by citral. With a focus on transient receptor potential activation, we examined the effect of citral on glutamatergic spontaneous excitatory transmission using the whole-cell patch-clamp technique to SG neurons in adult rat spinal cord slices. Bath-applied citral for 3 min increased the frequency of spontaneous excitatory postsynaptic current in a concentration-dependent manner (half-maximal effective concentration=0.58 mM), with a small increase in its amplitude. The spontaneous excitatory postsynaptic current frequency increase produced by citral was repeated at a time interval of 30 min, albeit this action recovered with a slow time course after washout. The presynaptic effect of citral was inhibited by TRPA1 antagonist HC-030031, but not by voltage-gated Na-channel blocker tetrodotoxin, TRPV1 antagonist capsazepine, and TRPM8 antagonist BCTC. It is concluded that citral increases spontaneous L-glutamate release in SG neurons by activating TRPA1 channels. Considering that the SG plays a pivotal role in modulating nociceptive transmission from the periphery, the citral activity could contribute toward at least a part of the modulation.

GABA-A receptor antagonists increase firing, bursting and synchrony of spontaneous activity in neuronal networks grown on microelectrode arrays: a step towards chemical "fingerprinting"

EPA Science Inventory

Assessment of effects on spontaneous network activity in neurons grown on MEAs is a proposed method to screen chemicals for potential neurotoxicity. In addition, differential effects on network activity (chemical "fingerprints") could be used to classify chemical modes of action....

Complexin Mutants Reveal Partial Segregation between Recycling Pathways That Drive Evoked and Spontaneous Neurotransmission

PubMed Central

Sabeva, Nadezhda; Cho, Richard W.; Vasin, Alexander; Gonzalez, Agustin; Littleton, J. Troy

2017-01-01

Synaptic vesicles fuse at morphological specializations in the presynaptic terminal termed active zones (AZs). Vesicle fusion can occur spontaneously or in response to an action potential. Following fusion, vesicles are retrieved and recycled within nerve terminals. It is still unclear whether vesicles that fuse spontaneously or following evoked release share similar recycling mechanisms. Genetic deletion of the SNARE-binding protein complexin dramatically increases spontaneous fusion, with the protein serving as the synaptic vesicle fusion clamp at Drosophila synapses. We examined synaptic vesicle recycling pathways at complexin null neuromuscular junctions, where spontaneous release is dramatically enhanced. We combined loading of the lipophilic dye FM1–43 with photoconversion, electron microscopy, and electrophysiology to monitor evoked and spontaneous recycling vesicle pools. We found that the total number of recycling vesicles was equal to those retrieved through spontaneous and evoked pools, suggesting that retrieval following fusion is partially segregated for spontaneous and evoked release. In addition, the kinetics of FM1–43 destaining and synaptic depression measured in the presence of the vesicle-refilling blocker bafilomycin indicated that spontaneous and evoked recycling pools partially intermix during the release process. Finally, FM1–43 photoconversion combined with electron microscopy analysis indicated that spontaneous recycling preferentially involves synaptic vesicles in the vicinity of AZs, whereas vesicles recycled following evoked release involve a larger intraterminal pool. Together, these results suggest that spontaneous and evoked vesicles use separable recycling pathways and then partially intermix during subsequent rounds of fusion. SIGNIFICANCE STATEMENT Neurotransmitter release involves fusion of synaptic vesicles with the plasma membrane in response to an action potential, or spontaneously in the absence of stimulation. Upon fusion, vesicles are retrieved and recycled, and it is unclear whether recycling pathways for evoked and spontaneous vesicles are segregated after fusion. We addressed this question by taking advantage of preparations lacking the synaptic protein complexin, which have elevated spontaneous release that enables reliable tracking of the spontaneous recycling pool. Our results suggest that spontaneous and evoked recycling pathways are segregated during the retrieval process but can partially intermix during stimulation. PMID:28077717

Role of calcium stores and membrane voltage in the generation of slow wave action potentials in guinea-pig gastric pylorus

PubMed Central

Van Helden, D F; Imtiaz, M S; Nurgaliyeva, K; von der Weid, P-Y; Dosen, P J

2000-01-01

Intracellular recordings made in single bundle strips of a visceral smooth muscle revealed rhythmic spontaneous membrane depolarizations termed slow waves (SWs). These exhibited ‘pacemaker’ and ‘regenerative’ components composed of summations of more elementary events termed spontaneous transient depolarizations (STDs). STDs and SWs persisted in the presence of tetrodotoxin, nifedipine and ryanodine, and upon brief exposure to Ca2+-free Cd2+-containing solutions; they were enhanced by ACh and blocked by BAPTA AM, cyclopiazonic acid and caffeine. SWs were also inhibited in heparin-loaded strips. SWs were observed over a wide range of membrane potentials (e.g. −80 to −45 mV) with increased frequencies at more depolarized potentials. Regular spontaneous SW activity in this preparation began after 1–3 h superfusion of the tissue with physiological saline following the dissection procedure. Membrane depolarization applied before the onset of this activity induced bursts of STD-like events (termed the ‘initial’ response) which, when larger than threshold levels initiated regenerative responses. The combined initial-regenerative waveform was termed the SW-like action potential. Voltage-induced responses exhibited large variable latencies (typical range 0.3–4 s), refractory periods of ≈11 s and a pharmacology that was indistinguishable from those of STDs and spontaneous SWs. The data indicate that SWs arise through more elementary inositol 1,4,5-trisphosphate (IP3) receptor-induced Ca2+ release events which rhythmically synchronize to trigger regenerative Ca2+ release and induce inward current across the plasmalemma. The finding that action potentials, which were indistinguishable from SWs, could be evoked by depolarization suggests that membrane potential modulates IP3 production. Voltage feedback on intracellular IP3-sensitive Ca2+ release is likely to have a major influence on the generation and propagation of SWs. PMID:10747196

Mechanisms underlying odorant-induced and spontaneous calcium signals in olfactory receptor neurons of spiny lobsters, Panulirus argus.

PubMed

Tadesse, Tizeta; Derby, Charles D; Schmidt, Manfred

2014-01-01

We determined if a newly developed antennule slice preparation allows studying chemosensory properties of spiny lobster olfactory receptor neurons under in situ conditions with Ca(2+) imaging. We show that chemical stimuli reach the dendrites of olfactory receptor neurons but not their somata, and that odorant-induced Ca(2+) signals in the somata are sufficiently stable over time to allow stimulation with a substantial number of odorants. Pharmacological manipulations served to elucidate the source of odorant-induced Ca(2+) transients and spontaneous Ca(2+) oscillations in the somata of olfactory receptor neurons. Both Ca(2+) signals are primarily mediated by an influx of extracellular Ca(2+) through voltage-activated Ca(2+) channels that can be blocked by CoCl2 and the L-type Ca(2+) channel blocker verapamil. Intracellular Ca(2+) stores contribute little to odorant-induced Ca(2+) transients and spontaneous Ca(2+) oscillations. The odorant-induced Ca(2+) transients as well as the spontaneous Ca(2+) oscillations depend on action potentials mediated by Na(+) channels that are largely TTX-insensitive but blocked by the local anesthetics tetracaine and lidocaine. Collectively, these results corroborate the conclusion that odorant-induced Ca(2+) transients and spontaneous Ca(2+) oscillations in the somata of olfactory receptor neurons closely reflect action potential activity associated with odorant-induced phasic-tonic responses and spontaneous bursting, respectively. Therefore, both types of Ca(2+) signals represent experimentally accessible proxies of spiking.

Methamphetamine Regulation of Firing Activity of Dopamine Neurons

PubMed Central

Lin, Min; Sambo, Danielle

2016-01-01

Methamphetamine (METH) is a substrate for the dopamine transporter that increases extracellular dopamine levels by competing with dopamine uptake and increasing reverse transport of dopamine via the transporter. METH has also been shown to alter the excitability of dopamine neurons. The mechanism of METH regulation of the intrinsic firing behaviors of dopamine neurons is less understood. Here we identified an unexpected and unique property of METH on the regulation of firing activity of mouse dopamine neurons. METH produced a transient augmentation of spontaneous spike activity of midbrain dopamine neurons that was followed by a progressive reduction of spontaneous spike activity. Inspection of action potential morphology revealed that METH increased the half-width and produced larger coefficients of variation of the interspike interval, suggesting that METH exposure affected the activity of voltage-dependent potassium channels in these neurons. Since METH has been shown to affect Ca2+ homeostasis, the unexpected findings that METH broadened the action potential and decreased the amplitude of afterhyperpolarization led us to ask whether METH alters the activity of Ca2+-activated potassium (BK) channels. First, we identified BK channels in dopamine neurons by their voltage dependence and their response to a BK channel blocker or opener. While METH suppressed the amplitude of BK channel-mediated unitary currents, the BK channel opener NS1619 attenuated the effects of METH on action potential broadening, afterhyperpolarization repression, and spontaneous spike activity reduction. Live-cell total internal reflection fluorescence microscopy, electrophysiology, and biochemical analysis suggest METH exposure decreased the activity of BK channels by decreasing BK-α subunit levels at the plasma membrane. SIGNIFICANCE STATEMENT Methamphetamine (METH) competes with dopamine uptake, increases dopamine efflux via the dopamine transporter, and affects the excitability of dopamine neurons. Here, we identified an unexpected property of METH on dopamine neuron firing activity. METH transiently increased the spontaneous spike activity of dopamine neurons followed by a progressive reduction of the spontaneous spike activity. METH broadened the action potentials, increased coefficients of variation of the interspike interval, and decreased the amplitude of afterhyperpolarization, which are consistent with changes in the activity of Ca2+-activated potassium (BK) channels. We found that METH decreased the activity of BK channels by stimulating BK-α subunit trafficking. Thus, METH modulation of dopamine neurotransmission and resulting behavioral responses is, in part, due to METH regulation of BK channel activity. PMID:27707972

The modulation effects of d-amphetamine and procaine on the spontaneously generated action potentials in the central neuron of snail, Achatina fulica Ferussac.

PubMed

Lin, Chia-Hsien; Tsai, Ming-Cheng

2005-05-01

The modulation effects of d-amphetamine and procaine on the spontaneously generated action potentials were studied on the RP1 central neuron of giant African snails (Achatina fulica Ferussac). Extra-cellular application of d-amphetamine or procaine reversibly elicited bursts of potential (BoP). Prazosin, propranolol, atropine or d-tubocurarine did not alter the BoP elicited by either d-amphetamine or procaine. KT-5720 or H89 (protein kinase A inhibitors) blocked d-amphetamine-elicited BoP, whereas they did not block the procaine-elicited BoP. U73122, neomycin (phospholipase C inhibitors) blocked the procaine-elicited BoP, whereas they did not block the d-amphetamine-elicited BoP in the same neuron. These results suggest that BoP elicited by d-amphetamine or procaine were associated with protein kinase A and phospholipase C activity in the neuron.

High sensitivity of spontaneous spike frequency to sodium leak current in a Lymnaea pacemaker neuron.

PubMed

Lu, T Z; Kostelecki, W; Sun, C L F; Dong, N; Pérez Velázquez, J L; Feng, Z-P

2016-12-01

The spontaneous rhythmic firing of action potentials in pacemaker neurons depends on the biophysical properties of voltage-gated ion channels and background leak currents. The background leak current includes a large K + and a small Na + component. We previously reported that a Na + -leak current via U-type channels is required to generate spontaneous action potential firing in the identified respiratory pacemaker neuron, RPeD1, in the freshwater pond snail Lymnaea stagnalis. We further investigated the functional significance of the background Na + current in rhythmic spiking of RPeD1 neurons. Whole-cell patch-clamp recording and computational modeling approaches were carried out in isolated RPeD1 neurons. The whole-cell current of the major ion channel components in RPeD1 neurons were characterized, and a conductance-based computational model of the rhythmic pacemaker activity was simulated with the experimental measurements. We found that the spiking rate is more sensitive to changes in the Na + leak current as compared to the K + leak current, suggesting a robust function of Na + leak current in regulating spontaneous neuronal firing activity. Our study provides new insight into our current understanding of the role of Na + leak current in intrinsic properties of pacemaker neurons. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Spontaneous activity of isolated dopaminergic periglomerular cells of the main olfactory bulb.

PubMed

Puopolo, Michelino; Bean, Bruce P; Raviola, Elio

2005-11-01

We examined the electrophysiological properties of a population of identified dopaminergic periglomerular cells of the main olfactory bulb using transgenic mice in which catecholaminergic neurons expressed human placental alkaline phosphatase (PLAP) on the outer surface of the plasma membrane. After acute dissociation, living dopaminergic periglomerular cells were identified by a fluorescently labeled monoclonal antibody to PLAP. In current-clamp mode, dopaminergic periglomerular cells spontaneously generated action potentials in a rhythmic fashion with an average frequency of 8 Hz. The hyperpolarization-activated cation current (Ih) did not seem important for pacemaking because blocking the current with ZD 7288 or Cs+ had little effect on spontaneous firing. To investigate what ionic currents do drive pacemaking, we performed action-potential-clamp experiments using records of pacemaking as voltage command in voltage-clamp experiments. We found that substantial TTX-sensitive Na+ current flows during the interspike depolarization. In addition, substantial Ca2+ current flowed during the interspike interval, and blocking Ca2+ current hyperpolarized the neurons and stopped spontaneous firing. These results show that dopaminergic periglomerular cells have intrinsic pacemaking activity, supporting the possibility that they can maintain a tonic release of dopamine to modulate the sensitivity of the olfactory system during odor detection. Calcium entry into these neurons provides electrical drive for pacemaking as well as triggering transmitter release.

Synchronization of action potentials during low-magnesium-induced bursting

PubMed Central

Johnson, Sarah E.; Hudson, John L.

2015-01-01

The relationship between mono- and polysynaptic strength and action potential synchronization was explored using a reduced external Mg2+ model. Single and dual whole cell patch-clamp recordings were performed in hippocampal cultures in three concentrations of external Mg2+. In decreased Mg2+ medium, the individual cells transitioned to spontaneous bursting behavior. In lowered Mg2+ media the larger excitatory synaptic events were observed more frequently and fewer transmission failures occurred, suggesting strengthened synaptic transmission. The event synchronization was calculated for the neural action potentials of the cell pairs, and it increased in media where Mg2+ concentration was lowered. Analysis of surrogate data where bursting was present, but no direct or indirect connections existed between the neurons, showed minimal action potential synchronization. This suggests the synchronization of action potentials is a product of the strengthening synaptic connections within neuronal networks. PMID:25609103

Synchronization of action potentials during low-magnesium-induced bursting.

PubMed

Johnson, Sarah E; Hudson, John L; Kapur, Jaideep

2015-04-01

The relationship between mono- and polysynaptic strength and action potential synchronization was explored using a reduced external Mg(2+) model. Single and dual whole cell patch-clamp recordings were performed in hippocampal cultures in three concentrations of external Mg(2+). In decreased Mg(2+) medium, the individual cells transitioned to spontaneous bursting behavior. In lowered Mg(2+) media the larger excitatory synaptic events were observed more frequently and fewer transmission failures occurred, suggesting strengthened synaptic transmission. The event synchronization was calculated for the neural action potentials of the cell pairs, and it increased in media where Mg(2+) concentration was lowered. Analysis of surrogate data where bursting was present, but no direct or indirect connections existed between the neurons, showed minimal action potential synchronization. This suggests the synchronization of action potentials is a product of the strengthening synaptic connections within neuronal networks. Copyright © 2015 the American Physiological Society.

A four-component model of the action potential in mouse detrusor smooth muscle cell

PubMed Central

Brain, Keith L.; Young, John S.; Manchanda, Rohit

2018-01-01

Background and hypothesis Detrusor smooth muscle cells (DSMCs) of the urinary bladder are electrically connected to one another via gap junctions and form a three dimensional syncytium. DSMCs exhibit spontaneous electrical activity, including passive depolarizations and action potentials. The shapes of spontaneous action potentials (sAPs) observed from a single DSM cell can vary widely. The biophysical origins of this variability, and the precise components which contribute to the complex shapes observed are not known. To address these questions, the basic components which constitute the sAPs were investigated. We hypothesized that linear combinations of scaled versions of these basic components can produce sAP shapes observed in the syncytium. Methods and results The basic components were identified as spontaneous evoked junction potentials (sEJP), native AP (nAP), slow after hyperpolarization (sAHP) and very slow after hyperpolarization (vsAHP). The experimental recordings were grouped into two sets: a training data set and a testing data set. A training set was used to estimate the components, and a test set to evaluate the efficiency of the estimated components. We found that a linear combination of the identified components when appropriately amplified and time shifted replicated various AP shapes to a high degree of similarity, as quantified by the root mean square error (RMSE) measure. Conclusions We conclude that the four basic components—sEJP, nAP, sAHP, and vsAHP—identified and isolated in this work are necessary and sufficient to replicate all varieties of the sAPs recorded experimentally in DSMCs. This model has the potential to generate testable hypotheses that can help identify the physiological processes underlying various features of the sAPs. Further, this model also provides a means to classify the sAPs into various shape classes. PMID:29351282

A four-component model of the action potential in mouse detrusor smooth muscle cell.

PubMed

Padmakumar, Mithun; Brain, Keith L; Young, John S; Manchanda, Rohit

2018-01-01

Detrusor smooth muscle cells (DSMCs) of the urinary bladder are electrically connected to one another via gap junctions and form a three dimensional syncytium. DSMCs exhibit spontaneous electrical activity, including passive depolarizations and action potentials. The shapes of spontaneous action potentials (sAPs) observed from a single DSM cell can vary widely. The biophysical origins of this variability, and the precise components which contribute to the complex shapes observed are not known. To address these questions, the basic components which constitute the sAPs were investigated. We hypothesized that linear combinations of scaled versions of these basic components can produce sAP shapes observed in the syncytium. The basic components were identified as spontaneous evoked junction potentials (sEJP), native AP (nAP), slow after hyperpolarization (sAHP) and very slow after hyperpolarization (vsAHP). The experimental recordings were grouped into two sets: a training data set and a testing data set. A training set was used to estimate the components, and a test set to evaluate the efficiency of the estimated components. We found that a linear combination of the identified components when appropriately amplified and time shifted replicated various AP shapes to a high degree of similarity, as quantified by the root mean square error (RMSE) measure. We conclude that the four basic components-sEJP, nAP, sAHP, and vsAHP-identified and isolated in this work are necessary and sufficient to replicate all varieties of the sAPs recorded experimentally in DSMCs. This model has the potential to generate testable hypotheses that can help identify the physiological processes underlying various features of the sAPs. Further, this model also provides a means to classify the sAPs into various shape classes.

Observing Fearful Faces Leads to Visuo-Spatial Perspective Taking

ERIC Educational Resources Information Center

Zwickel, Jan; Muller, Hermann J.

2010-01-01

A number of recent studies suggested that visuo-spatial perspective taking (VSPT) occurs spontaneously when viewing either a human body or an action by an agent. However, it remains unclear whether VSPT is caused by the observation of an (potential) action or occurs because the observer infers from certain cues that another mind is present…

Distinct effects of CGRP on typical and atypical smooth muscle cells involved in generating spontaneous contractions in the mouse renal pelvis

PubMed Central

Hashitani, Hikaru; Lang, Richard J; Mitsui, Retsu; Mabuchi, Yoshio; Suzuki, Hikaru

2009-01-01

Background and purpose: We investigated the cellular mechanisms underlying spontaneous contractions in the mouse renal pelvis, regulated by calcitonin gene-related peptide (CGRP). Experimental approach: Spontaneous contractions, action potentials and Ca2+ transients in typical and atypical smooth muscle cells (TSMCs and ATSMCs) within the renal pelvis wall were recorded separately using tension and intracellular microelectrode recording techniques and Fluo-4 Ca2+ imaging. Immunohistochemical and electron microscopic studies were also carried out. Key results: Bundles of CGRP containing transient receptor potential cation channel, subfamily V, member 1-positive sensory nerves were situated near both TSMCs and ATSMCs. Nerve stimulation reduced the frequency but augmented the amplitude and duration of spontaneous phasic contractions, action potentials and Ca2+ transients in TSMCs. CGRP and agents increasing internal cyclic adenosine monophosphate (cAMP) mimicked the nerve-mediated modulation of TSMC activity and suppressed ATSMCs Ca2+ transients. Membrane hyperpolarization induced by CGRP or cAMP stimulators was blocked by glibenclamide, while their negative chronotropic effects were less affected. Glibenclamide enhanced TSMC Ca2+ transients but inhibited ATSMC Ca2+ transients, while both 5-hydroxydecanoate and diazoxide, a blocker and opener of mitochondrial ATP-sensitive K+ channels, respectively, reduced the Ca2+ transient frequency in both TSMCs and ATSMCs. Inhibition of mitochondrial function blocked ATSMCs Ca2+ transients and inhibited spontaneous excitation of TSMCs. Conclusions and implications: The negative chronotropic effects of CGRP result primarily from suppression of ATSMC Ca2+ transients rather than opening of plasmalemmal ATP-sensitive K+ channels in TSMCs. The positive inotropic effects of CGRP may derive from activation of TSMC L-type Ca2+ channels. Mitochondrial Ca2+ handling in ATSMCs also plays a critical role in generating Ca2+ transients. PMID:20050194

Effects of changing the ionic environment on passive and active membrane properties of pregnant rat uterus

PubMed Central

Abe, Y.

1971-01-01

1. In pregnant rat myometrium electrotonic potentials, produced by externally applied current, were recorded intracellularly. 2. The space constant, λ, was 1·8 mm, the time constant, τm, 120 msec. The values obtained on the 7th day and on the 20th day of pregnancy were the same. 3. The magnitude of the electrotonic potential and the time constant of the membrane were increased in the absence of potassium from the external solution and decreased by excess potassium. 4. The magnitude of the electrotonic potential and the time constant of the membrane were increased by the replacement of chloride with C6H5SO3- or SO42-, and decreased with NO3- or I- replacement. 5. When the sodium chloride was replaced with sucrose (16·7 mM sodium remaining in the buffers) the spontaneous spikes deteriorated and activity stopped within 30 min. However, for periods up to 4 hr, a spike of larger amplitude and faster rate of rise than in normal solution could be evoked when a depolarizing current was applied. 6. When the external calcium concentration was raised (5 and 10 mM) the amplitude and the rate of rise of the evoked spike were increased. They were decreased by reducing calcium. In zero calcium spontaneous activity stopped within 15 min. 7. The effects of calcium deficiency were much less marked and slower in onset when, simultaneously, the sodium concentration was reduced to 16·7 mM. 8. When calcium was replaced with strontium (2·5 mM), the membrane was depolarized and the duration of the spontaneous and evoked action potential was prolonged, mainly due to a slowed rate of repolarization. When the concentration of strontium was raised to 7·5 or 12·5 mM the membrane was hyperpolarized, the duration of the action potential became short and the amplitude of the spike was increased. 9. Addition of barium or the replacement of calcium with barium caused depolarization and oscillatory membrane activity. However, a spike could be evoked by applying conditioning hyperpolarization. 10. Manganese abolished the spontaneous and evoked spike. Tetrodotoxin had no effect. 11. The results show that rat uterus has cable-like properties. The action potential may be due to calcium entry, while sodium, by influencing the membrane potential in competition with calcium, may be involved in the spontaneous spike generation and the spread of excitation. PMID:5103422

Inhibition of spontaneous activity of rabbit atrioventricular node cells by KB-R7943 and inhibitors of sarcoplasmic reticulum Ca2+ ATPase

PubMed Central

Cheng, Hongwei; Smith, Godfrey L.; Hancox, Jules C.; Orchard, Clive H.

2011-01-01

The atrioventricular node (AVN) can act as a subsidiary cardiac pacemaker if the sinoatrial node fails. In this study, we investigated the effects of the Na–Ca exchange (NCX) inhibitor KB-R7943, and inhibition of the sarcoplasmic reticulum calcium ATPase (SERCA), using thapsigargin or cyclopiazonic acid (CPA), on spontaneous action potentials (APs) and [Ca2+]i transients from cells isolated from the rabbit AVN. Spontaneous [Ca2+]i transients were monitored from undialysed AVN cells at 37 °C using Fluo-4. In separate experiments, spontaneous APs and ionic currents were recorded using the whole-cell patch clamp technique. Rapid application of 5 μM KB-R7943 slowed or stopped spontaneous APs and [Ca2+]i transients. However, in voltage clamp experiments in addition to blocking NCX current (INCX) KB-R7943 partially inhibited L-type calcium current (ICa,L). Rapid reduction of external [Na+] also abolished spontaneous activity. Inhibition of SERCA (using 2.5 μM thapsigargin or 30 μM CPA) also slowed or stopped spontaneous APs and [Ca2+]i transients. Our findings are consistent with the hypothesis that sarcoplasmic reticulum (SR) Ca2+ release influences spontaneous activity in AVN cells, and that this occurs via [Ca2+]i-activated INCX; however, the inhibitory action of KB-R7943 on ICa,L means that care is required in the interpretation of data obtained using this compound. PMID:21163524

Which nerve conduction parameters can predict spontaneous electromyographic activity in carpal tunnel syndrome?

PubMed

Chang, Chia-Wei; Lee, Wei-Ju; Liao, Yi-Chu; Chang, Ming-Hong

2013-11-01

We investigate electrodiagnostic markers to determine which parameters are the best predictors of spontaneous electromyographic (EMG) activity in carpal tunnel syndrome (CTS). We enrolled 229 patients with clinically proven and nerve conduction study (NCS)-proven CTS, as well as 100 normal control subjects. All subjects were evaluated using electrodiagnostic techniques, including median distal sensory latencies (DSLs), sensory nerve action potentials (SNAPs), distal motor latencies (DMLs), compound muscle action potentials (CMAPs), forearm median nerve conduction velocities (FMCVs) and wrist-palm motor conduction velocities (W-P MCVs). All CTS patients underwent EMG examination of the abductor pollicis brevis (APB) muscle, and the presence or absence of spontaneous EMG activities was recorded. Normal limits were determined by calculating the means ± 2 standard deviations from the control data. Associations between parameters from the NCS and EMG findings were investigated. In patients with clinically diagnosed CTS, abnormal median CMAP amplitudes were the best predictors of spontaneous activity during EMG examination (p<0.001; OR 36.58; 95% CI 15.85-84.43). If the median CMAP amplitude was ≤ 2.1 mV, the rate of occurrence of spontaneous EMG activity was >95% (positive predictive rate >95%). If the median CMAP amplitude was higher than the normal limit (>4.9 mV), the rate of no spontaneous EMG activity was >94% (negative predictive rate >94%). An abnormal SNAP amplitude was the second best predictor of spontaneous EMG activity (p<0.001; OR 4.13; 95% CI 2.16-7.90), and an abnormal FMCV was the third best predictor (p=0.01; OR 2.10; 95% CI 1.20-3.67). No other nerve conduction parameters had significant power to predict spontaneous activity upon EMG examination. The CMAP amplitudes of the APB are the most powerful predictors of the occurrence of spontaneous EMG activity. Low CMAP amplitudes are strongly associated with spontaneous activity, whereas high CMAP amplitude are less associated with spontaneous activity, implying that needle EMG examination should be recommended for the detection of spontaneous activity in those CTS patients whose NCS reveals CMAP amplitudes between 2.1 mV and the lower normal limit (4.9mV in the present study). Using NCS, electromyographers can predict the presence of spontaneous EMG activity in CTS patients. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Spontaneous Action and Transformative Learning: Empirical Investigations and Pragmatist Reflections

ERIC Educational Resources Information Center

Nohl, Arnd-Michael

2009-01-01

Whereas present theories of transformative learning tend to focus on the rational and reflective actor, in this article it is suggested that spontaneous action may play a decisive role in transformative learning too. In the spontaneity of action, novelty finds its way into life, gains momentum, is respected by others and reflected by the actor.…

Cholesterol-dependent balance between evoked and spontaneous synaptic vesicle recycling

PubMed Central

Wasser, Catherine R; Ertunc, Mert; Liu, Xinran; Kavalali, Ege T

2007-01-01

Cholesterol is a prominent component of nerve terminals. To examine cholesterol's role in central neurotransmission, we treated hippocampal cultures with methyl-β-cyclodextrin, which reversibly binds cholesterol, or mevastatin, an inhibitor of cholesterol biosynthesis, to deplete cholesterol. We also used hippocampal cultures from Niemann-Pick type C1-deficient mice defective in intracellular cholesterol trafficking. These conditions revealed an augmentation in spontaneous neurotransmission detected electrically and an increase in spontaneous vesicle endocytosis judged by horseradish peroxidase uptake after cholesterol depletion by methyl-β-cyclodextrin. In contrast, responses evoked by action potentials and hypertonicity were severely impaired after the same treatments. The increase in spontaneous vesicle recycling and the decrease in evoked neurotransmission were reversible upon cholesterol addition. Cholesterol removal did not impact on the low level of evoked neurotransmission seen in the absence of synaptic vesicle SNARE protein synaptobrevin-2 whereas the increase in spontaneous fusion remained. These results suggest that synaptic cholesterol balances evoked and spontaneous neurotransmission by hindering spontaneous synaptic vesicle turnover and sustaining evoked exo-endocytosis. PMID:17170046

Axonal propagation of simple and complex spikes in cerebellar Purkinje neurons.

PubMed

Khaliq, Zayd M; Raman, Indira M

2005-01-12

In cerebellar Purkinje neurons, the reliability of propagation of high-frequency simple spikes and spikelets of complex spikes is likely to regulate inhibition of Purkinje target neurons. To test the extent to which a one-to-one correspondence exists between somatic and axonal spikes, we made dual somatic and axonal recordings from Purkinje neurons in mouse cerebellar slices. Somatic action potentials were recorded with a whole-cell pipette, and the corresponding axonal signals were recorded extracellularly with a loose-patch pipette. Propagation of spontaneous and evoked simple spikes was highly reliable. At somatic firing rates of approximately 200 spikes/sec, <10% of spikes failed to propagate, with failures becoming more frequent only at maximal somatic firing rates (approximately 260 spikes/sec). Complex spikes were elicited by climbing fiber stimulation, and their somatic waveforms were modulated by tonic current injection, as well as by paired stimulation to depress the underlying EPSCs. Across conditions, the mean number of propagating action potentials remained just above two spikes per climbing fiber stimulation, but the instantaneous frequency of the propagating spikes changed, from approximately 375 Hz during somatic hyperpolarizations that silenced spontaneous firing to approximately 150 Hz during spontaneous activity. The probability of propagation of individual spikelets could be described quantitatively as a saturating function of spikelet amplitude, rate of rise, or preceding interspike interval. The results suggest that ion channels of Purkinje axons are adapted to produce extremely short refractory periods and that brief bursts of forward-propagating action potentials generated by complex spikes may contribute transiently to inhibition of postsynaptic neurons.

Initiation and blocking of the action potential in an axon in weak ultrasonic or microwave fields

NASA Astrophysics Data System (ADS)

Shneider, M. N.; Pekker, M.

2014-05-01

In this paper, we analyze the effect of the redistribution of the transmembrane ion channels in an axon caused by longitudinal acoustic vibrations of the membrane. These oscillations can be excited by an external source of ultrasound and weak microwave radiation interacting with the charges sitting on the surface of the lipid membrane. It is shown, using the Hodgkin-Huxley model of the axon, that the density redistribution of transmembrane sodium channels may reduce the threshold of the action potential, up to its spontaneous initiation. At the significant redistribution of sodium channels in the membrane, the rarefaction zones of the transmembrane channel density are formed, blocking the propagation of the action potential. Blocking the action potential propagation along the axon is shown to cause anesthesia in the example case of a squid axon. Various approaches to experimental observation of the effects considered in this paper are discussed.

Serotonin increases synaptic activity in olfactory bulb glomeruli

PubMed Central

Brill, Julia; Shao, Zuoyi; Puche, Adam C.; Wachowiak, Matt

2016-01-01

Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range. PMID:26655822

Serotonin increases synaptic activity in olfactory bulb glomeruli.

PubMed

Brill, Julia; Shao, Zuoyi; Puche, Adam C; Wachowiak, Matt; Shipley, Michael T

2016-03-01

Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range. Copyright © 2016 the American Physiological Society.

Prejunctional and postjunctional actions of heptanol and 18 beta-glycyrretinic acid in the rodent vas deferens.

PubMed

Rahman, Faisal; Manchanda, Rohit; Brain, Keith L

2009-06-15

Heptanol and 18 beta-glycyrrhetinic acid (18 beta GA) block gap junctions, but have other actions on transmitter release that have not been characterised. This study investigates the prejunctional and postjunctional effects of these compounds in guinea pig and mouse vas deferens using intracellular electrophysiological recording and confocal Ca(2+) imaging of sympathetic nerve terminals. In mice, heptanol (2 mM) reversibly decreased the amplitude of purinergic excitatory junction potentials (EJPs; 52+/-5%, P<0.05) while having little effect on spontaneous excitatory junction potentials (sEJPs). Heptanol (2 mM) reversibly abolished the nerve terminal Ca(2+) transient in 52% of terminals. 18 beta GA (10 microM) decreased the mean EJP amplitude, and increased input resistance in both mouse (137+/-17%, P<0.05) and guinea pig (354+/-50%, P<0.001) vas deferens indicating gap junction blockade. Further, 18 beta GA increased the sEJP frequency significantly in guinea pigs (by 71+/-25%, P<0.05) and in 5 out of 6 tissues in mice (19+/-3%, P<0.05). Moreover, 18 beta GA depolarised cells from both mice (11+/-1%, P<0.01) and guinea pigs (8+/-1%, P<0.005). Therefore, we conclude that heptanol (2 mM) decreases neurotransmitter release (given the decrease in EJP amplitude) by abolishing the nerve terminal action potential in a proportion of nerve terminals. 18 betaGA (10 microM) effectively blocks the gap junctions, but the increase in sEJP frequency suggests an additional prejunctional effect, which might involve the induction of spontaneous nerve terminal action potentials.

Relationship between auditory thresholds, central spontaneous activity and hair cell loss after acoustic trauma

PubMed Central

Mulders, W.H.A.M.; Ding, D.; Salvi, R.; Robertson, D.

2011-01-01

Acoustic trauma caused by exposure to a very loud sound increases spontaneous activity in central auditory structures such as the inferior colliculus. This hyperactivity has been suggested as a neural substrate for tinnitus, a phantom hearing sensation. In previous studies we have described a tentative link between the frequency region of hearing impairment and the corresponding tonotopic regions in the inferior colliculus showing hyperactivity. In this study we further investigated the relationship between cochlear compound action potential threshold loss, cochlear outer and inner hair cell loss and central hyperactivity in inferior colliculus of guinea pigs. Two weeks after a 10 kHz pure tone acoustic trauma, a tight relationship was demonstrated between the frequency region of compound action potential threshold loss and frequency regions in the inferior colliculus showing hyperactivity. Extending the duration of the acoustic trauma from 1 to 2 h did not result in significant increases in final cochlear threshold loss, but did result in a further increase of spontaneous firing rates in the inferior colliculus. Interestingly, hair cell loss was not present in the frequency regions where elevated cochlear thresholds and central hyperactivity were measured, suggesting that subtle changes in hair cell or primary afferent neural function are sufficient for central hyperactivity to be triggered and maintained. PMID:21491427

Increased firing frequency of spontaneous action potentials in cerebellar Purkinje neurons of db/db mice results from altered auto-rhythmicity and diminished GABAergic tonic inhibition.

PubMed

Forero-Vivas, María E; Hernández-Cruz, Arturo

2014-01-01

The hormone leptin, by binding to hypothalamic receptors, suppresses food intake and decreases body adiposity. Leptin receptors are also widely expressed in extra-hypothalamic areas such as hippocampus, amygdala and cerebellum, where leptin modulates synaptic transmission. Here we show that a defective leptin receptor affects the electrophysiological properties of cerebellar Purkinje neurons (PNs). PNs from (db/db) mice recorded in cerebellar slices display a higher firing rate of spontaneous action potentials than PNs from wild type (WT) mice. Blockade of GABAergic tonic inhibition with bicuculline in WT mice changes the firing pattern from continuous, uninterrupted spiking into bursting firing, but bicuculline does not produce these alterations in db/db neurons, suggesting that they receive a weaker GABAergic inhibitory input. Our results also show that the intrinsic firing properties (auto-rhythmicity) of WT and db/db PNs are different. Tonic firing of PNs, the only efferent output from the cerebellar cortex, is a persistent signal to downstream cerebellar targets. The significance of leptin modulation of PNs spontaneous firing is not known. Also, it is not clear if the increased excitability of cerebellar PNs in db/db mice results from hyperglycemia or from the lack of leptin signaling, since both conditions coexist in the db/db strain.

Spontaneous Facial Actions Map onto Emotional Experiences in a Non-social Context: Toward a Component-Based Approach

PubMed Central

Namba, Shushi; Kabir, Russell S.; Miyatani, Makoto; Nakao, Takashi

2017-01-01

While numerous studies have examined the relationships between facial actions and emotions, they have yet to account for the ways that specific spontaneous facial expressions map onto emotional experiences induced without expressive intent. Moreover, previous studies emphasized that a fine-grained investigation of facial components could establish the coherence of facial actions with actual internal states. Therefore, this study aimed to accumulate evidence for the correspondence between spontaneous facial components and emotional experiences. We reinvestigated data from previous research which secretly recorded spontaneous facial expressions of Japanese participants as they watched film clips designed to evoke four different target emotions: surprise, amusement, disgust, and sadness. The participants rated their emotional experiences via a self-reported questionnaire of 16 emotions. These spontaneous facial expressions were coded using the Facial Action Coding System, the gold standard for classifying visible facial movements. We corroborated each facial action that was present in the emotional experiences by applying stepwise regression models. The results found that spontaneous facial components occurred in ways that cohere to their evolutionary functions based on the rating values of emotional experiences (e.g., the inner brow raiser might be involved in the evaluation of novelty). This study provided new empirical evidence for the correspondence between each spontaneous facial component and first-person internal states of emotion as reported by the expresser. PMID:28522979

Prospective controlled trial comparing colostomy irrigation with "spontaneous-action" method.

PubMed

Williams, N S; Johnston, D

1980-07-12

Thirty randomly selected patients with permanent colostomies entered a prospective controlled trial comparing colostomy irrigation with spontaneous action. Each patient was interviewed and examined before irrigation was begun and again after the technique had been used for three months. Each then reverted to spontaneous action for a further three months and was then reassessed. Eight patients abandoned irrigation and 22 (73%) adhered to the protocol. Irrigation caused no mishaps or complications. The mean time spent managing the stoma was 45 +/- SEM 9 min/24 hours during spontaneous action and 53 +/- 9 min/24 hours during irrigation. This difference was not significant. The numbers of bowel actions weekly were 13 +/ SEM 2 during spontaneous action and 6 +/- 1 during irrigation (p < 0.01). Irrigation reduced odour and flatus in 20 patients and enabled 12 out of 18 to stop using drugs and seven to discard their appliance. Irrigation also improved the social life of 18 patients and the working conditions of eight out of 14. These finding show that some patients may not be suitable for irrigation but that for many it is better than the conventional British method of colostomy management. With modern apparatus the technique is safe.

Prospective controlled trial comparing colostomy irrigation with "spontaneous-action" method.

PubMed Central

Williams, N S; Johnston, D

1980-01-01

Thirty randomly selected patients with permanent colostomies entered a prospective controlled trial comparing colostomy irrigation with spontaneous action. Each patient was interviewed and examined before irrigation was begun and again after the technique had been used for three months. Each then reverted to spontaneous action for a further three months and was then reassessed. Eight patients abandoned irrigation and 22 (73%) adhered to the protocol. Irrigation caused no mishaps or complications. The mean time spent managing the stoma was 45 +/- SEM 9 min/24 hours during spontaneous action and 53 +/- 9 min/24 hours during irrigation. This difference was not significant. The numbers of bowel actions weekly were 13 +/ SEM 2 during spontaneous action and 6 +/- 1 during irrigation (p < 0.01). Irrigation reduced odour and flatus in 20 patients and enabled 12 out of 18 to stop using drugs and seven to discard their appliance. Irrigation also improved the social life of 18 patients and the working conditions of eight out of 14. These finding show that some patients may not be suitable for irrigation but that for many it is better than the conventional British method of colostomy management. With modern apparatus the technique is safe. PMID:7000249

Blocking the BK Channel Impedes Acquisition of Trace Eyeblink Conditioning

ERIC Educational Resources Information Center

Matthews, Elizabeth A.; Disterhoft, John F.

2009-01-01

Big-K[superscript +] conductance (BK)-channel mediated fast afterhyperpolarizations (AHPs) following action potentials are reduced after eyeblink conditioning. Blocking BK channels with paxilline increases evoked firing frequency in vitro and spontaneous pyramidal activity in vivo. To examine how increased excitability after BK-channel blockade…

Development of micro-electrode array based tests for neurotoxicity: assessment of interlaboratory reproducibility with neuroactive chemicals

EPA Science Inventory

Neuronal assemblies within the Central Nervous System (CNS) produce spontaneous or stimulus-evoked electrophysiological activity that can be monitored and quantified in terms of action potential patterns. Such patterns provide a sensitive endpoint to detect effects of chemicals, ...

Action potential-based MEA platform for in vitro screening of drug-induced cardiotoxicity using human iPSCs and rat neonatal myocytes.

PubMed

Jans, Danny; Callewaert, Geert; Krylychkina, Olga; Hoffman, Luis; Gullo, Francesco; Prodanov, Dimiter; Braeken, Dries

2017-09-01

Drug-induced cardiotoxicity poses a negative impact on public health and drug development. Cardiac safety pharmacology issues urged for the preclinical assessment of drug-induced ventricular arrhythmia leading to the design of several in vitro electrophysiological screening assays. In general, patch clamp systems allow for intracellular recordings, while multi-electrode array (MEA) technology detect extracellular activity. Here, we demonstrate a complementary metal oxide semiconductor (CMOS)-based MEA system as a reliable platform for non-invasive, long-term intracellular recording of cardiac action potentials at high resolution. Quinidine (8 concentrations from 10 -7 to 2.10 -5 M) and verapamil (7 concentrations from 10 -11 to 10 -5 M) were tested for dose-dependent responses in a network of cardiomyocytes. Electrophysiological parameters, such as the action potential duration (APD), rates of depolarization and repolarization and beating frequency were assessed. In hiPSC, quinidine prolonged APD with EC 50 of 2.2·10 -6 M. Further analysis indicated a multifactorial action potential prolongation by quinidine: (1) decreasing fast repolarization with IC 50 of 1.1·10 -6 M; (2) reducing maximum upstroke velocity with IC 50 of 2.6·10 -6 M; and (3) suppressing spontaneous activity with EC 50 of 3.8·10 -6 M. In rat neonatal cardiomyocytes, verapamil blocked spontaneous activity with EC 50 of 5.3·10 -8 M and prolonged the APD with EC 50 of 2.5·10 -8 M. Verapamil reduced rates of fast depolarization and repolarization with IC 50 s of 1.8 and 2.2·10 -7 M, respectively. In conclusion, the proposed action potential-based MEA platform offers high quality and stable long-term recordings with high information content allowing to characterize multi-ion channel blocking drugs. We anticipate application of the system as a screening platform to efficiently and cost-effectively test drugs for cardiac safety. Copyright © 2017 Elsevier Inc. All rights reserved.

Multidimensional Skyrme-density-functional study of the spontaneous fission of 238U

DOE PAGES

Sadhukhan, J.; Mazurek, K.; Dobaczewski, J.; ...

2015-01-01

We determined the spontaneous fission lifetime of 238U by a minimization of the action integral in a three-dimensional space of collective variables. Apart from the mass-distribution multipole moments Q 20 (elongation) and Q 30 (left–right asymmetry), we also considered the pairing-fluctuation parameter λ 2 as a collective coordinate. The collective potential was obtained self-consistently using the Skyrme energy density functional SkM*. The inertia tensor was obtained within the nonperturbative cranking approximation to the adiabatic time-dependent Hartree–Fock–Bogoliubov approach. As a result, the pairing-fluctuation parameter λ 2 allowed us to control the pairing gap along the fission path, which significantly changed themore » spontaneous fission lifetime.« less

Microscopic modeling of mass and charge distributions in the spontaneous fission of 240Pu

DOE PAGES

Sandhukhan, Jhilam; Nazarewicz, Witold; Schunck, Nicolas

2016-01-20

Here, we propose a methodology to calculate microscopically the mass and charge distributions of spontaneous fission yields. We combine the multidimensional minimization of collective action for fission with stochastic Langevin dynamics to track the relevant fission paths from the ground-state configuration up to scission. The nuclear potential energy and collective inertia governing the tunneling motion are obtained with nuclear density functional theory in the collective space of shape deformations and pairing. Moreover, we obtain a quantitative agreement with experimental data and find that both the charge and mass distributions in the spontaneous fission of 240Pu are sensitive both to themore » dissipation in collective motion and to adiabatic fission characteristics.« less

Bearing Witness: Citizen Journalism and Human Rights Issues

ERIC Educational Resources Information Center

Allan, Stuart; Sonwalkar, Prasun; Carter, Cynthia

2007-01-01

This article assesses the potential of online news reporting to create discursive spaces for emphatic engagement--of bearing witness--at a distance, especially where human rights violations are concerned. Taking as its focus the emergent forms and practices of citizen journalism, it examines the spontaneous actions of ordinary people compelled to…

Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles

PubMed Central

Leitz, Jeremy; Kavalali, Ege T

2014-01-01

Presynaptic terminals release neurotransmitters spontaneously in a manner that can be regulated by Ca2+. However, the mechanisms underlying this regulation are poorly understood because the inherent stochasticity and low probability of spontaneous fusion events has curtailed their visualization at individual release sites. Here, using pH-sensitive optical probes targeted to synaptic vesicles, we visualized single spontaneous fusion events and found that they are retrieved extremely rapidly with faster re-acidification kinetics than their action potential-evoked counterparts. These fusion events were coupled to postsynaptic NMDA receptor-driven Ca2+ signals, and at elevated Ca2+ concentrations there was an increase in the number of vesicles that would undergo fusion. Furthermore, spontaneous vesicle fusion propensity in a synapse was Ca2+-dependent but regulated autonomously: independent of evoked fusion probability at the same synapse. Taken together, these results expand classical quantal analysis to incorporate endocytic and exocytic phases of single fusion events and uncover autonomous regulation of spontaneous fusion. DOI: http://dx.doi.org/10.7554/eLife.03658.001 PMID:25415052

Improvisation and the self-organization of multiple musical bodies.

PubMed

Walton, Ashley E; Richardson, Michael J; Langland-Hassan, Peter; Chemero, Anthony

2015-01-01

Understanding everyday behavior relies heavily upon understanding our ability to improvise, how we are able to continuously anticipate and adapt in order to coordinate with our environment and others. Here we consider the ability of musicians to improvise, where they must spontaneously coordinate their actions with co-performers in order to produce novel musical expressions. Investigations of this behavior have traditionally focused on describing the organization of cognitive structures. The focus, here, however, is on the ability of the time-evolving patterns of inter-musician movement coordination as revealed by the mathematical tools of complex dynamical systems to provide a new understanding of what potentiates the novelty of spontaneous musical action. We demonstrate this approach through the application of cross wavelet spectral analysis, which isolates the strength and patterning of the behavioral coordination that occurs between improvising musicians across a range of nested time-scales. Revealing the sophistication of the previously unexplored dynamics of movement coordination between improvising musicians is an important step toward understanding how creative musical expressions emerge from the spontaneous coordination of multiple musical bodies.

Improvisation and the self-organization of multiple musical bodies

PubMed Central

Walton, Ashley E.; Richardson, Michael J.; Langland-Hassan, Peter; Chemero, Anthony

2015-01-01

Understanding everyday behavior relies heavily upon understanding our ability to improvise, how we are able to continuously anticipate and adapt in order to coordinate with our environment and others. Here we consider the ability of musicians to improvise, where they must spontaneously coordinate their actions with co-performers in order to produce novel musical expressions. Investigations of this behavior have traditionally focused on describing the organization of cognitive structures. The focus, here, however, is on the ability of the time-evolving patterns of inter-musician movement coordination as revealed by the mathematical tools of complex dynamical systems to provide a new understanding of what potentiates the novelty of spontaneous musical action. We demonstrate this approach through the application of cross wavelet spectral analysis, which isolates the strength and patterning of the behavioral coordination that occurs between improvising musicians across a range of nested time-scales. Revealing the sophistication of the previously unexplored dynamics of movement coordination between improvising musicians is an important step toward understanding how creative musical expressions emerge from the spontaneous coordination of multiple musical bodies. PMID:25941499

Triggered Firing and Atrial Fibrillation in Transgenic Mice With Selective Atrial Fibrosis Induced by Overexpression of TGF-β1

PubMed Central

Choi, Eue-Keun; Chang, Po-Cheng; Lee, Young-Soo; Lin, Shien-Fong; Zhu, Wuqiang; Maruyama, Mitsunori; Fishbein, Michael C.; Chen, Zhenhui; der Lohe, Michael Rubart-von; Field, Loren J.; Chen, Peng-Sheng

2013-01-01

Background Calcium transient triggered firing (CTTF) is induced by large intracellular calcium (Cai) transient and short action potential duration (APD). We hypothesized that CTTF underlies the mechanisms of early afterdepolarization (EAD) and spontaneous recurrent atrial fibrillation (AF) in transgenic (Tx) mice with overexpression of transforming growth factor β1 (TGF-β1). Methods and Results MHC-TGFcys33ser Tx mice develop atrial fibrosis because of elevated levels of TGF-β1. We studied membrane potential and Cai transients of isolated superfused atria from Tx and wild-type (Wt) littermates. Short APD and persistently elevated Cai transients promoted spontaneous repetitive EADs, triggered activity and spontaneous AF after cessation of burst pacing in Tx but not Wt atria (39% vs. 0%, P=0.008). We were able to map optically 4 episodes of spontaneous AF re-initiation. All first and second beats of spontaneous AF originated from the right atrium (4/4, 100%), which is more severely fibrotic than the left atrium. Ryanodine and thapsigargin inhibited spontaneous re-initiation of AF in all 7 Tx atria tested. Western blotting showed no significant changes of calsequestrin or sarco/endoplasmic reticulum Ca2+-ATPase 2a. Conclusions Spontaneous AF may occur in the Tx atrium because of CTTF, characterized by APD shortening, prolonged Cai transient, EAD and triggered activity. Inhibition of Ca2+ release from the sarcoplasmic reticulum suppressed spontaneous AF. Our results indicate that CTTF is an important arrhythmogenic mechanism in TGF-β1 Tx atria. PMID:22447020

Direct negative chronotropic action of desflurane on sinoatrial node pacemaker activity in the guinea pig heart.

PubMed

Kojima, Akiko; Ito, Yuki; Kitagawa, Hirotoshi; Matsuura, Hiroshi; Nosaka, Shuichi

2014-06-01

Desflurane inhalation is associated with sympathetic activation and concomitant increase in heart rate in humans and experimental animals. There is, however, little information concerning the direct effects of desflurane on electrical activity of sinoatrial node pacemaker cells that determines the intrinsic heart rate. Whole-cell patch-clamp experiments were conducted on guinea pig sinoatrial node pacemaker cells to record spontaneous action potentials and ionic currents contributing to sinoatrial node automaticity, namely, hyperpolarization-activated cation current (If), T-type and L-type Ca currents (ICa,T and ICa,L, respectively), Na/Ca exchange current (INCX), and rapidly and slowly activating delayed rectifier K currents (IKr and IKs, respectively). Electrocardiograms were recorded from ex vivo Langendorff-perfused hearts and in vivo hearts. Desflurane at 6 and 12% decreased spontaneous firing rate of sinoatrial node action potentials by 15.9% (n = 11) and 27.6% (n = 10), respectively, which was associated with 20.4% and 42.5% reductions in diastolic depolarization rate, respectively. Desflurane inhibited If, ICa,T, ICa,L, INCX, and IKs but had little effect on IKr. The negative chronotropic action of desflurane was reasonably well reproduced in sinoatrial node computer model. Desflurane reduced the heart rate in Langendorff-perfused hearts. High concentration (12%) of desflurane inhalation was associated with transient tachycardia, which was totally abolished by pretreatment with the β-adrenergic blocker propranolol. Desflurane has a direct negative chronotropic action on sinoatrial node pacemaking activity, which is mediated by its inhibitory action on multiple ionic currents. This direct inhibitory action of desflurane on sinoatrial node automaticity seems to be counteracted by sympathetic activation associated with desflurane inhalation in vivo.

Electrical and mechanical responses to inhibition of cell respiration in vascular smooth muscle of the rat portal vein.

PubMed

Ekmehag, B L

1989-09-01

Metabolic regulation of contractility in vascular smooth muscle was studied in the spontaneously active rat portal vein using respiratory depression by cyanide (0.2-2.0 mM) as a model for tissue hypoxia. Intracellular recordings of electrical activity were done with concomitant registration of force development. Average membrane potential in the absence of cyanide was -61 +/- 1 mV (n = 27). Addition of cyanide to normal Krebs solution resulted in a reduction of force amplitude and the number of action potentials per burst, with a relatively more pronounced effect on the mechanical activity. At moderate levels of inhibition of force amplitude the frequency of spontaneous bursts of action potentials transiently increased concomitant with a slight depolarization, but after prolonged (15-20 min) exposure to cyanide the membrane repolarized to the level prior to cyanide addition and the burst frequency decreased to be equal to or lower than that in the absence of cyanide. Higher concentrations of cyanide totally inhibited spontaneous mechanical and electrical activity. In contrast to the results with glucose, it was found that when beta-hydroxybutyrate was used as substrate the addition of 2 mM cyanide led to a marked hyperpolarization (13 +/- 1 mV) after total inhibition of spontaneous activity. The hyperpolarization was not prevented by administration of 4-aminopyridine (2.5 mM) or tetraethylammonium (4-6 mM) prior to the addition of cyanide. To investigate the effects of increased metabolic demand on the relation between force and membrane potential in cyanide-treated muscle, high-K+ (40 mM) contractures were studied. Contractures were associated with depolarization of 34 +/- 3 mV (n = 5). 1 mM cyanide reduced the amplitude of the contractures to about 9% of control with a moderate reduction in the amount of depolarization (28 +/- 1 mV, n = 5). It is concluded that the decrease of mechanical activity during respiratory inhibition may partly reflect a reduction in the number of spikes per burst but that other mechanisms, independent of membrane activity, also contribute to the inhibition. The increase of glycolysis during respiratory inhibition seems to prevent more pronounced changes in membrane potential.

Basophil FcεRI Expression in Chronic Spontaneous Urticaria: A Potential Immunological Predictor of Response to Omalizumab Therapy.

PubMed

Deza, Gustavo; Bertolín-Colilla, Marta; Pujol, Ramon M; Curto-Barredo, Laia; Soto, Dulce; García, Maribel; Hernández, Pilar; Gimeno, Ramon; Giménez-Arnau, Ana M

2017-06-09

Although the efficacy of omalizumab has been clearly demonstrated in the treatment of chronic spontaneous urticaria (CSU), its mechanism of action, which results in improvement in CSU symptoms, is not entirely understood. This study investigated the effect of omalizumab on expression of the high-affinity IgE receptor (FcεRI) on blood basophils from patients with active CSU, and its association with the clinical response. Patients exhibiting significant clinical improvement showed a sharp reduction in the levels of basophil FcεRI after 4 weeks, which was maintained throughout the total duration of the treatment. Such evolution was not observed in non-responder patients. Furthermore, non-responders showed significantly lower baseline levels of FcεRI than responders. Baseline basophil FcεRI expression was found to be a potential immunological predictor of response to omalizumab (100% sensitivity and 73.2% specificity). The results of this study contribute to our knowledge of the therapeutic benefit and mechanism of action of anti-IgE therapy in CSU.

Induction of temporally dissociated morphological and physiological differentiation of N1E-115 cells.

PubMed

Cosgrove, C; Cobbett, P

1991-07-01

Clonal cells derived from neural tumors have been widely used to study the processes of neuronal differentiation in vitro. The murine neuroblastoma clone N1E-115 has recently been shown to differentiate morphologically in response to removal of serum from the culture medium. In the present study, the nature and time course of electrophysiological differentiation of N1E-115 cells maintained in serum-free medium was examined. Differentiated cells had a higher resting potential and lower input conductance than nondifferentiated cells. Differentiated but not nondifferentiated cells generated current evoked action potentials, and differentiated cells fired spontaneous, repetitive action potentials after 13 days in serum-free medium. The rate of potential change during the depolarizing and repolarizing phases of the action potential became faster as the duration of maintenance of cells in serum-free medium increased. Remarkably, morphological differentiation appeared to be complete after exposure to serum-free medium for 5 days but electrophysiological differentiation was not complete until 13 days in this medium.

Extracellular NAD+ Suppresses Adrenergic Effects in the Atrial Myocardium of Rats during the Early Postnatal Ontogeny.

PubMed

Pustovit, K B; Ivanova, A D; Kuz'min, V S

2018-05-01

The effects of sympathetic cotransmitter NAD+ (10 μM) on bioelectric activity of the heart under conditions of adrenergic stimulation were studied on isolated spontaneously contracting preparations (without stimulation) of the right atrium from 2-7-day-old rats. Action potentials were recorded in the working myocardium using standard microelectrode technique. Perfusion of the right atrium with norepinephrine solution (1 μM) altered the configuration and significantly lengthened the action potentials. NAD + against the background of norepinephrine stimulation significantly decreased the duration of action potentials, in particular, at 25% repolarization. The effect of purine compounds NAD + , ATP, and adenosine on bioelectrical activity of the heart of newborn rats was studied under basal conditions (without norepinephrine stimulation). The effect of NAD + against the background of adrenergic stimulation was more pronounced than under basal conditions and was probably determined by suppression of I CaL , which can be the main mechanism of NAD + action on rat heart.

Use your head! Perception of action possibilities by means of an object attached to the head.

PubMed

Wagman, Jeffrey B; Hajnal, Alen

2016-03-01

Perceiving any environmental property requires spontaneously assembling a smart perceptual instrument-a task-specific measurement device assembled across potentially independent anatomical units. Previous research has shown that to a large degree, perception of a given environmental property is anatomically independent. We attempted to provide stronger evidence for this proposal by investigating perception by an organization of anatomical and inert components that likely requires the spontaneous assembly of a novel smart perceptual instrument-a rod attached to the head. Specifically, we compared cephalic and manual perception of whether an inclined surface affords standing on. In both conditions, perception reflected the action capabilities of the perceiver and not the appendage used to wield the rod. Such results provide stronger evidence for anatomical independence of perception within a given perceptual system and highlight that flexible task-specific detection units can be assembled across units that span the body and inert objects.

Atypical development of spontaneous social cognition in autism spectrum disorders.

PubMed

Senju, Atsushi

2013-02-01

Individuals with autism spectrum disorders (ASD) have profound impairment in the development of social interaction and communication. However, it is also known that some 'high-functioning' individuals with ASD show apparently typical capacity to process social information in a controlled experimental settings, despite their difficulties in daily life. The current paper overviews the spontaneous social cognition, spontaneous processing of social information in the absence of explicit instruction or task demand, in individuals with ASD. Three areas of the researches, false belief attribution, imitation/mimicry, and eye gaze processing, have been reviewed. The literatures suggest that high-functioning individuals with ASD (a) do not spontaneously attribute false belief to others, even though they can easily do so when explicitly instructed, (b) can imitate others' goal-directed actions under explicit instruction and show spontaneous mimicry of others' actions when they attend to the action, but are less likely to show spontaneous mimicry without the task structure to navigate attention to others' action and (c) can process others' gaze direction and shift attention to others' gaze directions, but fail to spontaneously attend to another person's eyes in social and communicative context, and less likely to be prompted to respond in response to perceived eye contact. These results are consistent with the claim that individuals with ASD do not spontaneously attend to socially relevant information, even though they can easily process the same information when their attention is navigated towards it. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Zonal variations in K+ currents in vestibular crista calyx terminals

PubMed Central

Meredith, Frances L.

2014-01-01

We developed a rodent crista slice to investigate regional variations in electrophysiological properties of vestibular afferent terminals. Thin transverse slices of the gerbil crista ampullaris were made and electrical properties of calyx terminals in central zones (CZ) and peripheral zones (PZ) compared with whole cell patch clamp. Spontaneous action potential firing was observed in 25% of current-clamp recordings and was either regular or irregular in both zones. Firing was abolished when extracellular choline replaced Na+ but persisted when hair cell mechanotransduction channels or calyx AMPA receptors were blocked. This suggests that ion channels intrinsic to the calyx can generate spontaneous firing. In response to depolarizing voltage steps, outward K+ currents were observed at potentials above −60 mV. K+ currents in PZ calyces showed significantly more inactivation than currents in CZ calyces. Underlying K+ channel populations contributing to these differences were investigated. The KCNQ channel blocker XE991 dihydrochloride blocked a slowly activating, sustained outward current in both PZ and CZ calyces, indicating the presence of KCNQ channels. Mean reduction was greatest in PZ calyces. XE991 also reduced action potential firing frequency in CZ and PZ calyces and broadened mean action potential width. The K+ channel blocker 4-aminopyridine (10–50 μM) blocked rapidly activating, moderately inactivating currents that were more prevalent in PZ calyces. α-Dendrotoxin, a selective blocker of KV1 channels, reduced outward currents in CZ calyces but not in PZ calyces. Regional variations in K+ conductances may contribute to different firing responses in calyx afferents. PMID:25343781

Zonal variations in K+ currents in vestibular crista calyx terminals.

PubMed

Meredith, Frances L; Rennie, Katherine J

2015-01-01

We developed a rodent crista slice to investigate regional variations in electrophysiological properties of vestibular afferent terminals. Thin transverse slices of the gerbil crista ampullaris were made and electrical properties of calyx terminals in central zones (CZ) and peripheral zones (PZ) compared with whole cell patch clamp. Spontaneous action potential firing was observed in 25% of current-clamp recordings and was either regular or irregular in both zones. Firing was abolished when extracellular choline replaced Na(+) but persisted when hair cell mechanotransduction channels or calyx AMPA receptors were blocked. This suggests that ion channels intrinsic to the calyx can generate spontaneous firing. In response to depolarizing voltage steps, outward K(+) currents were observed at potentials above -60 mV. K(+) currents in PZ calyces showed significantly more inactivation than currents in CZ calyces. Underlying K(+) channel populations contributing to these differences were investigated. The KCNQ channel blocker XE991 dihydrochloride blocked a slowly activating, sustained outward current in both PZ and CZ calyces, indicating the presence of KCNQ channels. Mean reduction was greatest in PZ calyces. XE991 also reduced action potential firing frequency in CZ and PZ calyces and broadened mean action potential width. The K(+) channel blocker 4-aminopyridine (10-50 μM) blocked rapidly activating, moderately inactivating currents that were more prevalent in PZ calyces. α-Dendrotoxin, a selective blocker of KV1 channels, reduced outward currents in CZ calyces but not in PZ calyces. Regional variations in K(+) conductances may contribute to different firing responses in calyx afferents. Copyright © 2015 the American Physiological Society.

Period doubling cascades of limit cycles in cardiac action potential models as precursors to chaotic early Afterdepolarizations.

PubMed

Kügler, Philipp; Bulelzai, M A K; Erhardt, André H

2017-04-04

Early afterdepolarizations (EADs) are pathological voltage oscillations during the repolarization phase of cardiac action potentials (APs). EADs are caused by drugs, oxidative stress or ion channel disease, and they are considered as potential precursors to cardiac arrhythmias in recent attempts to redefine the cardiac drug safety paradigm. The irregular behaviour of EADs observed in experiments has been previously attributed to chaotic EAD dynamics under periodic pacing, made possible by a homoclinic bifurcation in the fast subsystem of the deterministic AP system of differential equations. In this article we demonstrate that a homoclinic bifurcation in the fast subsystem of the action potential model is neither a necessary nor a sufficient condition for the genesis of chaotic EADs. We rather argue that a cascade of period doubling (PD) bifurcations of limit cycles in the full AP system paves the way to chaotic EAD dynamics across a variety of models including a) periodically paced and spontaneously active cardiomyocytes, b) periodically paced and non-active cardiomyocytes as well as c) unpaced and spontaneously active cardiomyocytes. Furthermore, our bifurcation analysis reveals that chaotic EAD dynamics may coexist in a stable manner with fully regular AP dynamics, where only the initial conditions decide which type of dynamics is displayed. EADs are a potential source of cardiac arrhythmias and hence are of relevance both from the viewpoint of drug cardiotoxicity testing and the treatment of cardiomyopathies. The model-independent association of chaotic EADs with period doubling cascades of limit cycles introduced in this article opens novel opportunities to study chaotic EADs by means of bifurcation control theory and inverse bifurcation analysis. Furthermore, our results may shed new light on the synchronization and propagation of chaotic EADs in homogeneous and heterogeneous multicellular and cardiac tissue preparations.

Screening Fluorescent Voltage Indicators with Spontaneously Spiking HEK Cells

PubMed Central

Venkatachalam, Veena; Kralj, Joel M.; Dib-Hajj, Sulayman D.; Waxman, Stephen G.; Cohen, Adam E.

2013-01-01

Development of improved fluorescent voltage indicators is a key challenge in neuroscience, but progress has been hampered by the low throughput of patch-clamp characterization. We introduce a line of non-fluorescent HEK cells that stably express NaV 1.3 and KIR 2.1 and generate spontaneous electrical action potentials. These cells enable rapid, electrode-free screening of speed and sensitivity of voltage sensitive dyes or fluorescent proteins on a standard fluorescence microscope. We screened a small library of mutants of archaerhodopsin 3 (Arch) in spiking HEK cells and identified two mutants with greater voltage-sensitivity than found in previously published Arch voltage indicators. PMID:24391999

Characterizing the complexity of spontaneous motor unit patterns of amyotrophic lateral sclerosis using approximate entropy

NASA Astrophysics Data System (ADS)

Zhou, Ping; Barkhaus, Paul E.; Zhang, Xu; Zev Rymer, William

2011-10-01

This paper presents a novel application of the approximate entropy (ApEn) measurement for characterizing spontaneous motor unit activity of amyotrophic lateral sclerosis (ALS) patients. High-density surface electromyography (EMG) was used to record spontaneous motor unit activity bilaterally from the thenar muscles of nine ALS subjects. Three distinct patterns of spontaneous motor unit activity (sporadic spikes, tonic spikes and high-frequency repetitive spikes) were observed. For each pattern, complexity was characterized by calculating the ApEn values of the representative signal segments. A sliding window over each segment was also introduced to quantify the dynamic changes in complexity for the different spontaneous motor unit patterns. We found that the ApEn values for the sporadic spikes were the highest, while those of the high-frequency repetitive spikes were the lowest. There is a significant difference in mean ApEn values between two arbitrary groups of the three spontaneous motor unit patterns (P < 0.001). The dynamic ApEn curve from the sliding window analysis is capable of tracking variations in EMG activity, thus providing a vivid, distinctive description for different patterns of spontaneous motor unit action potentials in terms of their complexity. These findings expand the existing knowledge of spontaneous motor unit activity in ALS beyond what was previously obtained using conventional linear methods such as firing rate or inter-spike interval statistics.

DELTAMETHRIN AND ESFENVALERATE INHIBIT SPONTANEOUS NETWORK ACTIVITY IN RAT CORTICAL NEURONS IN VITRO.

EPA Science Inventory

Understanding pyrethroid actions on neuronal networks will help to establish a mode of action for these compounds, which is needed for cumulative risk decisions under the Food Quality Protection Act of 1996. However, pyrethroid effects on spontaneous activity in networks of inter...

Action potential bursts in central snail neurons elicited by paeonol: roles of ionic currents

PubMed Central

Chen, Yi-hung; Lin, Pei-lin; Hsu, Hui-yu; Wu, Ya-ting; Yang, Han-yin; Lu, Dah-yuu; Huang, Shiang-suo; Hsieh, Ching-liang; Lin, Jaung-geng

2010-01-01

Aim: To investigate the effects of 2′-hydroxy-4′-methoxyacetophenone (paeonol) on the electrophysiological behavior of a central neuron (right parietal 4; RP4) of the giant African snail (Achatina fulica Ferussac). Methods: Intracellular recordings and the two-electrode voltage clamp method were used to study the effects of paeonol on the RP4 neuron. Results: The RP4 neuron generated spontaneous action potentials. Bath application of paeonol at a concentration of ≥500 μmol/L reversibly elicited action potential bursts in a concentration-dependent manner. Immersing the neurons in Co2+-substituted Ca2+-free solution did not block paeonol-elicited bursting. Pretreatment with the protein kinase A (PKA) inhibitor KT-5720 or the protein kinase C (PKC) inhibitor Ro 31-8220 did not affect the action potential bursts. Voltage-clamp studies revealed that paeonol at a concentration of 500 μmol/L had no remarkable effects on the total inward currents, whereas paeonol decreased the delayed rectifying K+ current (IKD) and the fast-inactivating K+ current (IA). Application of 4-aminopyridine (4-AP 5 mmol/L), an inhibitor of IA, or charybdotoxin 250 nmol/L, an inhibitor of the Ca2+-activated K+ current (IK(Ca)), failed to elicit action potential bursts, whereas tetraethylammonium chloride (TEA 50 mmol/L), an IKD blocker, successfully elicited action potential bursts. At a lower concentration of 5 mmol/L, TEA facilitated the induction of action potential bursts elicited by paeonol. Conclusion: Paeonol elicited a bursting firing pattern of action potentials in the RP4 neuron and this activity relates closely to the inhibitory effects of paeonol on the IKD. PMID:21042287

Abolishment of Spontaneous Flight Turns in Visually Responsive Drosophila.

PubMed

Ferris, Bennett Drew; Green, Jonathan; Maimon, Gaby

2018-01-22

Animals react rapidly to external stimuli, such as an approaching predator, but in other circumstances, they seem to act spontaneously, without any obvious external trigger. How do the neural processes mediating the execution of reflexive and spontaneous actions differ? We studied this question in tethered, flying Drosophila. We found that silencing a large but genetically defined set of non-motor neurons virtually eliminates spontaneous flight turns while preserving the tethered flies' ability to perform two types of visually evoked turns, demonstrating that, at least in flies, these two modes of action are almost completely dissociable. Copyright © 2017 Elsevier Ltd. All rights reserved.

A unified probabilistic framework for spontaneous facial action modeling and understanding.

PubMed

Tong, Yan; Chen, Jixu; Ji, Qiang

2010-02-01

Facial expression is a natural and powerful means of human communication. Recognizing spontaneous facial actions, however, is very challenging due to subtle facial deformation, frequent head movements, and ambiguous and uncertain facial motion measurements. Because of these challenges, current research in facial expression recognition is limited to posed expressions and often in frontal view. A spontaneous facial expression is characterized by rigid head movements and nonrigid facial muscular movements. More importantly, it is the coherent and consistent spatiotemporal interactions among rigid and nonrigid facial motions that produce a meaningful facial expression. Recognizing this fact, we introduce a unified probabilistic facial action model based on the Dynamic Bayesian network (DBN) to simultaneously and coherently represent rigid and nonrigid facial motions, their spatiotemporal dependencies, and their image measurements. Advanced machine learning methods are introduced to learn the model based on both training data and subjective prior knowledge. Given the model and the measurements of facial motions, facial action recognition is accomplished through probabilistic inference by systematically integrating visual measurements with the facial action model. Experiments show that compared to the state-of-the-art techniques, the proposed system yields significant improvements in recognizing both rigid and nonrigid facial motions, especially for spontaneous facial expressions.

Myocardial deletion of transcription factor CHF1/Hey2 results in altered myocyte action potential and mild conduction system expansion but does not alter conduction system function or promote spontaneous arrhythmias.

PubMed

Hartman, Matthew E; Liu, Yonggang; Zhu, Wei-Zhong; Chien, Wei-Ming; Weldy, Chad S; Fishman, Glenn I; Laflamme, Michael A; Chin, Michael T

2014-07-01

CHF1/Hey2 is a Notch-responsive basic helix-loop-helix transcription factor involved in cardiac development. Common variants in Hey2 are associated with Brugada syndrome. We hypothesized that absence of CHF1/Hey2 would result in abnormal cellular electrical activity, altered cardiac conduction system (CCS) development, and increased arrhythmogenesis. We isolated neonatal CHF/Hey2-knockout (KO) cardiac myocytes and measured action potentials and ion channel subunit gene expression. We also crossed myocardial-specific CHF1/Hey2-KO mice with cardiac conduction system LacZ reporter mice and stained for conduction system tissue. We also performed ambulatory ECG monitoring for arrhythmias and heart rate variability. Neonatal cardiomyocytes from CHF1/Hey2-KO mice demonstrate a 50% reduction in action potential dV/dT, a 50-75% reduction in SCN5A, KCNJ2, and CACNA1C ion channel subunit gene expression, and an increase in delayed afterdepolarizations from 0/min to 12/min. CHF1/Hey2 cKO CCS-lacZ mice have a ∼3-fold increase in amount of CCS tissue. Ambulatory ECG monitoring showed no difference in cardiac conduction, arrhythmias, or heart rate variability. Wild-type cells or animals were used in all experiments. CHF1/Hey2 may contribute to Brugada syndrome by influencing the expression of SCN5A and formation of the cardiac conduction system, but its absence does not cause baseline conduction defects or arrhythmias in the adult mouse.-Hartman, M. E., Liu, Y., Zhu, W.-Z., Chien, W.-M., Weldy, C. S., Fishman, G. I., Laflamme, M. A., Chin, M. T. Myocardial deletion of transcription factor CHF1/Hey2 results in altered myocyte action potential and mild conduction system expansion but does not alter conduction system function or promote spontaneous arrhythmias. © FASEB.

An Integrated Circuit for Simultaneous Extracellular Electrophysiology Recording and Optogenetic Neural Manipulation.

PubMed

Chen, Chang Hao; McCullagh, Elizabeth A; Pun, Sio Hang; Mak, Peng Un; Vai, Mang I; Mak, Pui In; Klug, Achim; Lei, Tim C

2017-03-01

The ability to record and to control action potential firing in neuronal circuits is critical to understand how the brain functions. The objective of this study is to develop a monolithic integrated circuit (IC) to record action potentials and simultaneously control action potential firing using optogenetics. A low-noise and high input impedance (or low input capacitance) neural recording amplifier is combined with a high current laser/light-emitting diode (LED) driver in a single IC. The low input capacitance of the amplifier (9.7 pF) was achieved by adding a dedicated unity gain stage optimized for high impedance metal electrodes. The input referred noise of the amplifier is [Formula: see text], which is lower than the estimated thermal noise of the metal electrode. Thus, the action potentials originating from a single neuron can be recorded with a signal-to-noise ratio of at least 6.6. The LED/laser current driver delivers a maximum current of 330 mA, which is adequate for optogenetic control. The functionality of the IC was tested with an anesthetized Mongolian gerbil and auditory stimulated action potentials were recorded from the inferior colliculus. Spontaneous firings of fifth (trigeminal) nerve fibers were also inhibited using the optogenetic protein Halorhodopsin. Moreover, a noise model of the system was derived to guide the design. A single IC to measure and control action potentials using optogenetic proteins is realized so that more complicated behavioral neuroscience research and the translational neural disorder treatments become possible in the future.

Activation of cannabinoid CB1 receptors modulates evoked action potentials in rat retinal ganglion cells.

PubMed

Jiang, Shu-Xia; Li, Qian; Wang, Xiao-Han; Li, Fang; Wang, Zhong-Feng

2013-08-25

Activation of cannabinoid CB1 receptors (CB1Rs) regulates a variety of physiological functions in the vertebrate retina through modulating various types of ion channels. The aim of the present study was to investigate the effects of this receptor on cell excitability of rat retinal ganglion cells (RGCs) in retinal slices using whole-cell patch-clamp techniques. The results showed that under current-clamped condition perfusing WIN55212-2 (WIN, 5 μmol/L), a CB1R agonist, did not significantly change the spontaneous firing frequency and resting membrane potential of RGCs. In the presence of cocktail synaptic blockers, including excitatory postsynaptic receptor blockers CNQX and D-APV, and inhibitory receptor blockers bicuculline and strychnine, perfusion of WIN (5 μmol/L) hardly changed the frequencies of evoked action potentials by a series of positive current injection (from +10 to +100 pA). Phase-plane plot analysis showed that both average threshold voltage for triggering action potential and delay time to reach threshold voltage were not affected by WIN. However, WIN significantly decreased +dV/dtmax and -dV/dtmax of action potentials, suggestive of reduced rising and descending velocities of action potentials. The effects of WIN were reversed by co-application of SR141716, a CB1R selective antagonist. Moreover, WIN did not influence resting membrane potential of RGCs with synaptic inputs being blocked. These results suggest that activation of CB1Rs may regulate intrinsic excitability of rat RGCs through modulating evoked action potentials.

The action of chlorphenesin carbamate on the frog spinal cord.

PubMed

Aihara, H; Kurachi, M; Nakane, S; Sasajima, M; Ohzeki, M

1980-02-01

Studies were carried out to elucidate the mechanism of action of chlorphenesin carbamate (CPC) and to compare the effect of the drug with that of mephenesin on the isolated bullfrog spinal cord. Ventral and dorsal root potentials were recorded by means of the sucrose-gap method. CPC caused marked hyperpolarizations and depressed spontaneous activities in both of the primary afferent terminals (PAT) and motoneurons (MN). These hyperpolarizations were observed even in high-Mg2+ and Ca2+-free Ringer's solution, suggesting that CPC has direct actions on PAT and MN. Various reflex potentials (dorsal and ventral root potentials elicited by stimulating dorsal and ventral root, respectively) tended to be depressed by CPC as well as by mephenesin. Excitatory amino acids (L-aspartic acid and L-glutamic acid) caused marked depolarizations in PAT and MN, and increased the firing rate in MN. CPC did not modify the depolarization but abolished the motoneuron firing induced by these amino acids. However, mephenesin reduced both the depolarization and the motoneuron firing. The dorsal and ventral root potentials evoked by tetanic stimulation (40 Hz) of the dorsal root were depressed by the drugs. These results indicate that CPC has an apparent depressing action on the spinal neuron, and this action may be ascribed to the slight hyperpolarization and/or the prolongation of refractory period.

Interactions between superficial and deep dorsal horn spinal cord neurons in the processing of nociceptive information.

PubMed

Petitjean, Hugues; Rodeau, Jean-Luc; Schlichter, Rémy

2012-12-01

In acute rat spinal cord slices, the application of capsaicin (5 μm, 90 s), an agonist of transient receptor potential vanilloid 1 receptors expressed by a subset of nociceptors that project to laminae I-II of the spinal cord dorsal horn, induced an increase in the frequency of spontaneous excitatory and spontaneous inhibitory postsynaptic currents in about half of the neurons in laminae II, III-IV and V. In the presence of tetrodotoxin, which blocks action potential generation and polysynaptic transmission, capsaicin increased the frequency of miniature excitatory postsynaptic currents in only 30% of lamina II neurons and had no effect on the frequency of miniature excitatory postsynaptic currents in laminae III-V or on the frequency of miniature inhibitory postsynaptic currents in laminae II-V. When the communication between lamina V and more superficial laminae was interrupted by performing a mechanical section between laminae IV and V, capsaicin induced an increase in spontaneous excitatory postsynaptic current frequency in laminae II-IV and an increase in spontaneous inhibitory postsynaptic current frequency in lamina II that were similar to those observed in intact slices. However, in laminae III-IV of transected slices, the increase in spontaneous inhibitory postsynaptic current frequency was virtually abolished. Our results indicate that nociceptive information conveyed by transient receptor potential vanilloid 1-expressing nociceptors is transmitted from lamina II to deeper laminae essentially by an excitatory pathway and that deep laminae exert a 'feedback' control over neurons in laminae III-IV by increasing inhibitory synaptic transmission in these laminae. Moreover, we provide evidence that laminae III-IV might play an important role in the processing of nociceptive information in the dorsal horn. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Intrinsic and integrative properties of substantia nigra pars reticulata neurons

PubMed Central

Zhou, Fu-Ming; Lee, Christian R.

2011-01-01

The GABA projection neurons of the substantia nigra pars reticulata (SNr) are output neurons for the basal ganglia and thus critical for movement control. Their most striking neurophysiological feature is sustained, spontaneous high frequency spike firing. A fundamental question is: what are the key ion channels supporting the remarkable firing capability in these neurons? Recent studies indicate that these neurons express tonically active TRPC3 channels that conduct a Na-dependent inward current even at hyperpolarized membrane potentials. When the membrane potential reaches −60 mV, a voltage-gated persistent sodium current (INaP) starts to activate, further depolarizing the membrane potential. At or slightly below −50 mV, the large transient voltage-activated sodium current (INaT) starts to activate and eventually triggers the rapid rising phase of action potentials. SNr GABA neurons have a higher density of (INaT), contributing to the faster rise and larger amplitude of action potentials, compared with the slow-spiking dopamine neurons. INaT also recovers from inactivation more quickly in SNr GABA neurons than in nigral dopamine neurons. In SNr GABA neurons, the rising phase of the action potential triggers the activation of high-threshold, inactivation-resistant Kv3-like channels that can rapidly repolarize the membrane. These intrinsic ion channels provide SNr GABA neurons with the ability to fire spontaneous and sustained high frequency spikes. Additionally, robust GABA inputs from direct pathway medium spiny neurons in the striatum and GABA neurons in the globus pallidus may inhibit and silence SNr GABA neurons, whereas glutamate synaptic input from the subthalamic nucleus may induce burst firing in SNr GABA neurons. Thus, afferent GABA and glutamate synaptic inputs sculpt the tonic high frequency firing of SNr GABA neurons and the consequent inhibition of their targets into an integrated motor control signal that is further fine-tuned by neuromodulators including dopamine, serotonin, endocannabinoids, and H2O2. PMID:21839148

[Conversion of sound into auditory nerve action potentials].

PubMed

Encke, J; Kreh, J; Völk, F; Hemmert, W

2016-11-01

Outer hair cells play a major role in the hearing process: they amplify the motion of the basilar membrane up to a 1000-fold and at the same time sharpen the excitation patterns. These patterns are converted by inner hair cells into action potentials of the auditory nerve. Outer hair cells are delicate structures and easily damaged, e. g., by overexposure to noise. Hearing aids can amplify the amplitude of the excitation patterns, but they cannot restore their degraded frequency selectivity. Noise overexposure also leads to delayed degeneration of auditory nerve fibers, particularly those with low a spontaneous rate, which are important for the coding of sound in noise. However, this loss cannot be diagnosed by pure-tone audiometry.

Dofetilide promotes repolarization abnormalities in perfused Guinea-pig heart.

PubMed

Osadchii, Oleg E

2012-12-01

Dofetilide is class III antiarrhythmic agent which prolongs cardiac action potential duration because of selective inhibition of I (Kr), the rapid component of the delayed rectifier K(+) current. Although clinical studies reported on proarrhythmic risk associated with dofetilide treatment, the contributing electrophysiological mechanisms remain poorly understood. This study was designed to determine if dofetilide-induced proarrhythmia may be attributed to abnormalities in ventricular repolarization and refractoriness. The monophasic action potential duration and effective refractory periods (ERP) were assessed at distinct epicardial and endocardial sites along with volume-conducted ECG recordings in isolated, perfused guinea-pig heart preparations. Dofetilide was found to produce the reverse rate-dependent prolongation of ventricular repolarization, increased the steepness of action potential duration rate adaptation, and amplified transepicardial variability in electrical restitution kinetics. Dofetilide also prolonged the T peak-to-end interval on ECG, and elicited a greater prolongation of endocardial than epicardial ERP, thereby increasing transmural dispersion of refractoriness. At epicardium, dofetilide prolonged action potential duration to a greater extent than ERP, thus extending the critical interval for ventricular re-excitation. This change was associated with triangulation of epicardial action potential because of greater dofetilide-induced prolonging effect at 90 % than 30 % repolarization. Premature ectopic beats and spontaneous short-lasting episodes of monomorphic ventricular tachycardia were observed in 44 % of dofetilide-treated heart preparations. Proarrhythmic potential of dofetilide in guinea-pig heart is attributed to steepened electrical restitution, increased transepicardial variability in electrical restitution kinetics, amplified transmural dispersion of refractoriness, increased critical interval for ventricular re-excitation, and triangulation of epicardial action potential.

Spontaneous bacteriocin resistance in Listeria monocytogenes as a susceptibility screen for identifying different mechanisms of resistance and modes of action by bacteriocins of lactic acid bacteria.

PubMed

Macwana, Sunita; Muriana, Peter M

2012-01-01

A practical system was devised for grouping bacteriocins of lactic acid bacteria (LAB) based on mode of action as determined by changes in inhibitory activity to spontaneously-acquired bacteriocin resistance (Bac(R)). Wild type Listeria monocytogenes 39-2 was sensitive to five bacteriocins produced by 3 genera of LAB: pediocin PA-1 and pediocin Bac3 (Pediococcus), lacticin FS97 and lacticin FS56 (Lactococcus), and curvaticin FS47 (Lactobacillus). A spontaneous Bac(R) derivative of L. monocytogenes 39-2 obtained by selective recovery against lacticin FS56 provided complete resistance to the bacteriocin made by Lactococcus lactis FS56. The lacticin FS56-resistant strain of L. monocyotgenes 39-2 was also cross-resistant to curvaticin FS47 and pediocin PA-1, but not to lacticin FS97 or pediocin Bac3. The same pattern of cross-resistance was also observed with Bac(R) isolates obtained with L. monocytogenes Scott A-2. A spontaneous mutation that renders a strain cross-resistant to different bacteriocins indicates that they share a common mechanism of resistance due to similar modes of action of the bacteriocins. Spontaneous resistance was acquired to other bacteriocins (in aggregate) by following the same procedure against which the Bac(R) strain was still sensitive. In subsequent challenge assays, mixtures of bacteriocins of different modes of action provided greater inhibition than mixtures of bacteriocins of the same mode of action (as determined by our screening method). This study identifies a methodical approach to classify bacteriocins into functional groups based on mechanism of resistance (i.e., mode of action) that could be used for identifying the best mixture of bacteriocins for use as biopreservatives. Copyright © 2011 Elsevier B.V. All rights reserved.

Spontaneous Release Regulates Synaptic Scaling in the Embryonic Spinal Network In Vivo

PubMed Central

Garcia-Bereguiain, Miguel Angel; Gonzalez-Islas, Carlos; Lindsly, Casie

2016-01-01

Homeostatic plasticity mechanisms maintain cellular or network spiking activity within a physiologically functional range through compensatory changes in synaptic strength or intrinsic cellular excitability. Synaptic scaling is one form of homeostatic plasticity that is triggered after blockade of spiking or neurotransmission in which the strengths of all synaptic inputs to a cell are multiplicatively scaled upward or downward in a compensatory fashion. We have shown previously that synaptic upscaling could be triggered in chick embryo spinal motoneurons by complete blockade of spiking or GABAA receptor (GABAAR) activation for 2 d in vivo. Here, we alter GABAAR activation in a more physiologically relevant manner by chronically adjusting presynaptic GABA release in vivo using nicotinic modulators or an mGluR2 agonist. Manipulating GABAAR activation in this way triggered scaling in a mechanistically similar manner to scaling induced by complete blockade of GABAARs. Remarkably, we find that altering action-potential (AP)-independent spontaneous release was able to fully account for the observed bidirectional scaling, whereas dramatic changes in spiking activity associated with spontaneous network activity had little effect on quantal amplitude. The reliance of scaling on an AP-independent process challenges the plasticity's relatedness to spiking in the living embryonic spinal network. Our findings have implications for the trigger and function of synaptic scaling and suggest that spontaneous release functions to regulate synaptic strength homeostatically in vivo. SIGNIFICANCE STATEMENT Homeostatic synaptic scaling is thought to prevent inappropriate levels of spiking activity through compensatory adjustments in the strength of synaptic inputs. Therefore, it is thought that perturbations in spike rate trigger scaling. Here, we find that dramatic changes in spiking activity in the embryonic spinal cord have little effect on synaptic scaling; conversely, alterations in GABAA receptor activation due to action-potential-independent GABA vesicle release can trigger scaling. The findings suggest that scaling in the living embryonic spinal cord functions to maintain synaptic strength and challenge the view that scaling acts to regulate spiking activity homeostatically. Finally, the results indicate that fetal exposure to drugs that influence GABA spontaneous release, such as nicotine, could profoundly affect synaptic maturation. PMID:27383600

Detecting acute neurotoxicity during platinum chemotherapy by neurophysiological assessment of motor nerve hyperexcitability

PubMed Central

2010-01-01

Background Platinum-based drugs, such as cisplatin and oxaliplatin, are well-known for inducing chronic sensory neuropathies but their acute and motor neurotoxicities are less well characterised. Use was made of nerve conduction studies and needle electromyography (EMG) to assess motor nerve excitability in cancer patients during their first treatment cycle with platinum-based chemotherapy in this study. Methods Twenty-nine adult cancer patients had a neurophysiological assessment either before oxaliplatin plus capecitabine, on days 2 to 4 or 14 to 20 after oxaliplatin plus capecitabine, or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin, undertaken by a neurophysiologist who was blinded to patient and treatment details. Patients completed a symptom questionnaire at the end of the treatment cycle. Results Abnormal spontaneous high frequency motor fibre action potentials were detected in 100% of patients (n = 6) and 72% of muscles (n = 22) on days 2 to 4 post-oxaliplatin, and in 25% of patients (n = 8) and 13% of muscles (n = 32) on days 14 to 20 post-oxaliplatin, but in none of the patients (n = 14) or muscles (n = 56) tested prior to oxaliplatin or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin. Repetitive compound motor action potentials were less sensitive and less specific than spontaneous high frequency motor fibre action potentials for detection of acute oxaliplatin-induced motor nerve hyperexcitability but were present in 71% of patients (n = 7) and 32% of muscles (n = 32) on days 2 to 4 after oxaliplatin treatment. Acute neurotoxicity symptoms, most commonly cold-induced paraesthesiae and jaw or throat tightness, were reported by all patients treated with oxaliplatin (n = 22) and none of those treated with carboplatin plus paclitaxel or cisplatin (n = 6). Conclusions Abnormal spontaneous high frequency motor fibre activity is a sensitive and specific endpoint of acute oxaliplatin-induced motor nerve hyperexcitability, detectable on EMG on days 2 to 4 post-treatment. Objective EMG assessment of motor nerve excitability could compliment patient-reported symptomatic endpoints of acute oxaliplatin-induced neurotoxicity in future studies. PMID:20731872

Effects of substance P on carotid chemoreceptor activity in the cat.

PubMed Central

McQueen, D S

1980-01-01

1. The influence of substance P (SP) on spontaneous chemosensory discharge and on responses of the carotid chemoreceptors to various drugs has been investigated in pentobarbitone anaesthetized casts in which chemoreceptor activity was recorded from the peripheral end of a sectioned sinus nerve. 2. After an initial slight inhibition during the first 5--15 sec following the injection, SP (0.1--100 microgram I.A.) caused a dose-related increase in discharge which lasted for 45--300 sec in artificially ventilated cats, discharge being increased by about 50% on average. The increase was of shorter duration when the animals were allowed to breathe spontaneously. 3. The delayed increase in discharge was not secondary to the hypotension caused by SP, nor was it entirely due to changes in bronchomotor tone resulting from direct or indirect actions of SP, although such changes contributed to the response. It was not possible to determine whether the excitation was due to a direct effect of SP on the chemoreceptors. 4. Chemosensory excitation evoked by NaCN (5 microgram I.A.) was potentiated during I.A. infusions of SP and also 10--20 min after SP (10 microgram I.A.) had been injected. In contrast, responses to ACh (50 microgram I.A.) were inhibited. These effects may be due to a nicotinic-blocking action of SP on the carotid chemoreceptors. It was also found that the inhibitory action of dopamine (5 microgram I.A.) was reduced during SP infusion whereas that of 5-HT (10 microgram I.A.) was potentiated. 5. A sample of crude SP had effects on spontaneous chemoreceptor discharge and responses to NaCN and ACh which were qualitatively similar to those obtained using synthetic SP. 6. The physiological significance of the results is discussed and it is concluded that the interpretation depends upon whether or not SP is present in the cat's carotid body. PMID:6157809

Functional coupling of TRPV4 channels and BK channels in regulating spontaneous contractions of the guinea pig urinary bladder.

PubMed

Isogai, Ayu; Lee, Ken; Mitsui, Retsu; Hashitani, Hikaru

2016-09-01

We investigated the role of TRPV4 channels (TRPV4) in regulating the contractility of detrusor smooth muscle (DSM) and muscularis mucosae (MM) of the urinary bladder. Distribution of TRPV4 in DSM and MM of guinea-pig bladders was examined by fluorescence immunohistochemistry. Changes in the contractility of DSM and MM bundles were measured using isometric tension recording. Intracellular Ca(2+) dynamics were visualized by Cal-520 fluorescent Ca(2+) imaging, while membrane potential changes were recorded using intracellular microelectrode technique. DSM and MM expressed TRPV4 immunoreactivity. GSK1016790A (GSK, 1 nM), a TRPV4 agonist, evoked a sustained contraction in both DSM and MM associated with a cessation of spontaneous phasic contractions in a manner sensitive to HC-067047 (10 μM), a TRPV4 antagonist. Iberiotoxin (100 nM) and paxilline (1 μM), large conductance Ca(2+)-activated K(+) (BK) channel blockers restored the spontaneous contractions in GSK. The sustained contractions in DSM and MM were reduced by nifedipine (10 μM), a blocker of L-type voltage-dependent Ca(2+) channels (LVDCCs) by about 40 % and by nominally Ca(2+)-free solution by some 90 %. GSK (1 nM) abolished spontaneous Ca(2+) transients, increased basal Ca(2+) levels and also prevented spontaneous action potential discharge associated with DSM membrane hyperpolarization. In conclusion, Ca(2+) influx through TRPV4 appears to activate BK channels to suppress spontaneous contractions and thus a functional coupling of TRPV4 with BK channels may act as a self-limiting mechanism for bladder contractility during its storage phase. Despite the membrane hyperpolarization in GSK, Ca(2+) entry mainly through TRPV4 develops the tonic contraction.

[Creation of a line of "depressed" mice from a selection of breeders exhibiting a behavioral helplessness].

PubMed

Vaugeois, J M; Costentin, J

1998-01-01

Antidepressants are used since 40 years. All presently used antidepressants have a slow onset of action and do not improve all patients; thus, there is an absolute need for new antidepressants. A variety of animal models, often based upon the monoaminergic theory of depressive disorders, has been used to screen the current antidepressants. In fact, the main focus of most of these animal models has been to predict the antidepressant potential i.e. to establish predictive validity. However, the evaluation of such animal models should also consider face validity, i.e. how closely the model resembles the human condition, and this should help to identify innovating medicines. Antidepressants, when taken by a healthy person, induce nothing more than side effects, unrelated to an action on mood, whereas they alleviate depressive symptomatology in depressed patients. We have speculated that genetically selected animal models would be closer to the human clinical situation than models based on standard laboratory strains. We have depicted here that marked differences exist between strains of mice in the amount of immobility i.e. "spontaneous helplessness" observed in the tail suspension test, a method used to screen potential antidepressants. We have studied the behavioural characteristics of mice selectively bred for spontaneous high or low immobility scores in the tail suspension test. Hopefully, these selectively bred lines will provide a novel approach to investigate behavioural, neurochemical and neuroendocrine correlates of antidepressant action.

Dynamical entrainment of corticospinal excitability during rhythmic movement observation: a Transcranial Magnetic Stimulation study.

PubMed

Varlet, Manuel; Novembre, Giacomo; Keller, Peter E

2017-06-01

Spontaneous modulations of corticospinal excitability during action observation have been interpreted as evidence for the activation of internal motor representations equivalent to the observed action. Alternatively or complementary to this perspective, growing evidence shows that motor activity during observation of rhythmic movements can be modulated by direct visuomotor couplings and dynamical entrainment. In-phase and anti-phase entrainment spontaneously occur, characterized by cyclic movements proceeding simultaneously in the same (in-phase) or opposite (anti-phase) direction. Here we investigate corticospinal excitability during the observation of vertical oscillations of an index finger using Transcranial Magnetic Stimulation (TMS). Motor-evoked potentials (MEPs) were recorded from participants' flexor and extensor muscles of the right index finger, placed in either a maximal steady flexion or extension position, with stimulations delivered at maximal flexion, maximal extension or mid-trajectory of the observed finger oscillations. Consistent with the occurrence of dynamical motor entrainment, increased and decreased MEP responses - suggesting the facilitation of stable in-phase and anti-phase relations but not an unstable 90° phase relation - were found in participants' flexors. Anti-phase motor facilitation contrasts with the activation of internal motor representation as it involves activity in the motor system opposite from activity required for the execution of the observed movement. These findings demonstrate the relevance of dynamical entrainment theories and methods for understanding spontaneous motor activity in the brain during action observation and the mechanisms underpinning coordinated movements during social interaction. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The motor cost of telling lies: electrocortical signatures and personality foundations of spontaneous deception.

PubMed

Panasiti, Maria Serena; Pavone, Enea F; Mancini, Alessandra; Merla, Arcangelo; Grisoni, Luigi; Aglioti, Salvatore M

2014-01-01

Although universal, lying is generally considered immoral behavior. Most neuroscience studies on lying sanction or instruct deceptive behaviors and thus might fail to acknowledge the significance of lie-related moral conflicts. By combining electroencephalogram (EEG) recordings with a novel paradigm in which participants decided freely whether to deceive another person, we have generated indices of the cognitive (reaction times and stimulus-locked event-related components) and moral (readiness potential and its correlations with deception-related personality traits) cost of spontaneous deception. Our data fail to support the consensus that deception is cognitively more demanding than truth telling, suggesting that spontaneous deception, as opposed to lying out of requirement, might not mandate additional cognitive workload. Interestingly, lying was associated with decreased motor readiness, an event-related potential (ERP) component that is linked to motor preparation of self-determined actions and modulated when we face moral dilemmas. Notably, this reduction was less extensive in manipulative participants and greater in those who cared highly about their impression management. Our study expands on previous findings on deception by associating a cortical marker of reduced preparation to act with individual differences in moral cognition.

Effect of acute stretch injury on action potential and network activity of rat neocortical neurons in culture.

PubMed

Magou, George C; Pfister, Bryan J; Berlin, Joshua R

2015-10-22

The basis for acute seizures following traumatic brain injury (TBI) remains unclear. Animal models of TBI have revealed acute hyperexcitablility in cortical neurons that could underlie seizure activity, but studying initiating events causing hyperexcitability is difficult in these models. In vitro models of stretch injury with cultured cortical neurons, a surrogate for TBI, allow facile investigation of cellular changes after injury but they have only demonstrated post-injury hypoexcitability. The goal of this study was to determine if neuronal hyperexcitability could be triggered by in vitro stretch injury. Controlled uniaxial stretch injury was delivered to a spatially delimited region of a spontaneously active network of cultured rat cortical neurons, yielding a region of stretch-injured neurons and adjacent regions of non-stretched neurons that did not directly experience stretch injury. Spontaneous electrical activity was measured in non-stretched and stretch-injured neurons, and in control neuronal networks not subjected to stretch injury. Non-stretched neurons in stretch-injured cultures displayed a three-fold increase in action potential firing rate and bursting activity 30-60 min post-injury. Stretch-injured neurons, however, displayed dramatically lower rates of action potential firing and bursting. These results demonstrate that acute hyperexcitability can be observed in non-stretched neurons located in regions adjacent to the site of stretch injury, consistent with reports that seizure activity can arise from regions surrounding the site of localized brain injury. Thus, this in vitro procedure for localized neuronal stretch injury may provide a model to study the earliest cellular changes in neuronal function associated with acute post-traumatic seizures. Copyright © 2015. Published by Elsevier B.V.

Mechanisms contributing to cluster formation in the inferior olivary nucleus in brainstem slices from postnatal mice

PubMed Central

Kølvraa, Mathias; Müller, Felix C; Jahnsen, Henrik; Rekling, Jens C

2014-01-01

Abstract The inferior olivary nucleus (IO) in in vitro slices from postnatal mice (P5.5–P15.5) spontaneously generates clusters of neurons with synchronous calcium transients, and intracellular recordings from IO neurons suggest that electrical coupling between neighbouring IO neurons may serve as a synchronizing mechanism. Here, we studied the cluster-forming mechanism and find that clusters overlap extensively with an overlap distribution that resembles the distribution for a random overlap model. The average somatodendritic field size of single curly IO neurons was ∼6400 μm2, which is slightly smaller than the average IO cluster size. Eighty-seven neurons with overlapping dendrites were estimated to be contained in the principal olive mean cluster size, and about six non-overlapping curly IO neurons could be contained within the largest clusters. Clusters could also be induced by iontophoresis with glutamate. Induced clusters were inhibited by tetrodotoxin, carbenoxelone and 18β-glycyrrhetinic acid, suggesting that sodium action potentials and electrical coupling are involved in glutamate-induced cluster formation, which could also be induced by activation of N-methyl-d-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Spikelets and a small transient depolarizing response were observed during glutamate-induced cluster formation. Calcium transients spread with decreasing velocity during cluster formation, and somatic action potentials and cluster formation are accompanied by large dendritic calcium transients. In conclusion, cluster formation depends on gap junctions, sodium action potentials and spontaneous clusters occur randomly throughout the IO. The relative slow signal spread during cluster formation, combined with a strong dendritic influx of calcium, may signify that active dendritic properties contribute to cluster formation. PMID:24042500

Mental arithmetic leads to multiple discrete changes from baseline in the firing patterns of human thalamic neurons.

PubMed

Kim, J H; Ohara, S; Lenz, F A

2009-04-01

Primate thalamic action potential bursts associated with low-threshold spikes (LTS) occur during waking sensory and motor activity. We now test the hypothesis that different firing and LTS burst characteristics occur during quiet wakefulness (spontaneous condition) versus mental arithmetic (counting condition). This hypothesis was tested by thalamic recordings during the surgical treatment of tremor. Across all neurons and epochs, preburst interspike intervals (ISIs) were bimodal at median values, consistent with the duration of type A and type B gamma-aminobutyric acid inhibitory postsynaptic potentials. Neuronal spike trains (117 neurons) were categorized by joint ISI distributions into those firing as LTS bursts (G, grouped), firing as single spikes (NG, nongrouped), or firing as single spikes with sporadic LTS bursting (I, intermediate). During the spontaneous condition (46 neurons) only I spike trains changed category. Overall, burst rates (BRs) were lower and firing rates (FRs) were higher during the counting versus the spontaneous condition. Spike trains in the G category sometimes changed to I and NG categories at the transition from the spontaneous to the counting condition, whereas those in the I category often changed to NG. Among spike trains that did not change category by condition, G spike trains had lower BRs during counting, whereas NG spike trains had higher FRs. BRs were significantly greater than zero for G and I categories during wakefulness (both conditions). The changes between the spontaneous and counting conditions are most pronounced for the I category, which may be a transitional firing pattern between the bursting (G) and relay modes of thalamic firing (NG).

Gap junctions between CA3 pyramidal cells contribute to network synchronization in neonatal hippocampus.

PubMed

Molchanova, Svetlana M; Huupponen, Johanna; Lauri, Sari E; Taira, Tomi

2016-08-01

Direct electrical coupling between neurons through gap junctions is prominent during development, when synaptic connectivity is scarce, providing the additional intercellular connectivity. However, functional studies of gap junctions are hampered by the unspecificity of pharmacological tools available. Here we have investigated gap-junctional coupling between CA3 pyramidal cells in neonatal hippocampus and its contribution to early network activity. Four different gap junction inhibitors, including the general blocker carbenoxolone, decreased the frequency of network activity bursts in CA3 area of hippocampus of P3-6 rats, suggesting the involvement of electrical connections in the generation of spontaneous network activity. In CA3 pyramidal cells, spikelets evoked by local stimulation of stratum oriens, were inhibited by carbenoxolone, but not by inhibitors of glutamatergic and GABAergic synaptic transmission, signifying the presence of electrical connectivity through axo-axonic gap junctions. Carbenoxolone also decreased the success rate of firing antidromic action potentials in response to stimulation, and changed the pattern of spontaneous action potential firing of CA3 pyramidal cells. Altogether, these data suggest that electrical coupling of CA3 pyramidal cells contribute to the generation of the early network events in neonatal hippocampus by modulating their firing pattern and synchronization. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inhibitory actions of methionine-enkephalin and morphine on the cat carotid chemoreceptors.

PubMed

McQueen, D S; Ribeiro, J A

1980-01-01

1 The effects of intracarotid injections of methionine-enkephalin (Met-enkephalin) and morphine on chemoreceptor activity recorded from the peripheral end of a sectioned carotid sinus nerve have been studied in cats anaesthetized with pentobarbitone. 2 Met-enkephalin caused a rapid, powerful, inhibition of spontaneous chemoreceptor discharge, the intensity and duration of which was dose-dependent. 3 Morphine was a less potent inhibitor of spontaneous chemoreceptor discharge, and the inhibition it evoked was rather variable and tended to be biphasic. Low doses of morphine caused a slight increase in discharge. 4 Naloxone (0.2 mg i.c.) slightly increased spontaneous discharge, greatly reduced the chemo-inhibition caused by morphine, and reduced the inhibitory effect of Met-enkephalin. A higher dose of naloxone (0.8 mg) caused a substantial reduction of the Met-enkephalin effect. 5 Chemo-excitation evoked by intracarotid injections of acetylcholine, CO2-saturated Locke solution, and sodium cyanide were only slightly and somewhat variably reduced following injections of Met-enkephalin, whereas the inhibitory effect of dopamine was potentiated. Following morphine administration, response to acetylcholine and sodium cyanide were reduced slightly, whereas those to CO2 and dopamine were potentiated. 6 Responses to acetylcholine and CO2 were slightly potentiated during infusion of Met-enkephalin (50 micrograms/min, i.c.) and the response to sodium cyanide was slightly reduced. 7 It is concluded that naloxone-sensitive opiate receptors are present in the cat carotid body; when activated they cause inhibition of spontaneous chemoreceptor discharge. The physiological role of these receptors and the identity of any endogenous ligand remains to be established.

The effects of gentamicin and penicillin/streptomycin on the electrophysiology of human induced pluripotent stem cell-derived cardiomyocytes in manual patch clamp and multi-electrode array system.

PubMed

Hyun, Soo-Wang; Kim, Bo-Ram; Lin, Dan; Hyun, Sung-Ae; Yoon, Seong Shoon; Seo, Joung-Wook

Cell culture media usually contains antibiotics including gentamicin or penicillin/streptomycin (PS) to protect cells from bacterial contamination. However, little is known about the effects of antibiotics on action potential and field potential parameters in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The present study examined the effects of gentamicin (10, 25, and 50μg/ml) and PS (50, 100, and 200U/μg/ml) on electrophysiological activity in spontaneously beating hiPSC-CMs using manual patch clamp and multi-electrode array. We also measured mRNA expression of cardiac ion channels in hiPSC-CMs grown in media with or without gentamicin (25μg/ml) using reverse transcription-polymerase chain reaction. We recorded action potential and field potential of hiPSC-CMs grown in the presence or absence of gentamicin or PS. We also observed action potential parameters in hiPSC-CMs after short-term treatment with these antibiotics. Changes in action potential and field potential parameters were observed in hiPSC-CMs grown in media containing gentamicin or PS. Treatment with PS also affected action potential parameters in hiPSC-CMs. In addition, the mRNA expression of cardiac sodium and potassium ion channels was significantly attenuated in hiPSC-CMs grown in the presence of gentamicin (25μg/ml). The present findings suggested that gentamicin should not be used in the culture media of hiPSC-CMs used for the measurement of electrophysiological parameters. Our findings also suggest that 100U/100μg/ml of PS are the maximum appropriate concentrations of these antibiotics for recording action potential waveform, because they did not influence action potential parameters in these cells. Copyright © 2017. Published by Elsevier Inc.

[Comutagenic action of sodium selenite and caffeine on S. typhimurium TA 1535 with its subsequent treatment by N-nitrosomethylurea].

PubMed

Balanski, R M

1988-01-01

The comutagenic activity of sodium selenite and caffeine was studied by the Ames test. Reproduction of S. typhimurium TA1535 for 4 h at 37 degrees C in the nutrient broth with sodium selenide (5 micrograms/ml) significantly increased sensitivity of bacterial cells to the mutagenic action of 2-3 mM N-nitrosomethylurea (NMU). When using threshold concentrations of NMU the potentiation of mutagenesis reached 625.2%. The addition of 0.19 mg/ml of caffeine to the nutrient medium also led (though the action was less pronounced) to an increase in sensitivity of bacterial cells to the NMU mutagenic action. Reproduction of S. typhimurium TA1535 in the medium containing sodium selenide and caffeine did not cause an increase in the frequency of spontaneous his+-revertant mutations.

Light-evoked hyperpolarization and silencing of neurons by conjugated polymers.

PubMed

Feyen, Paul; Colombo, Elisabetta; Endeman, Duco; Nova, Mattia; Laudato, Lucia; Martino, Nicola; Antognazza, Maria Rosa; Lanzani, Guglielmo; Benfenati, Fabio; Ghezzi, Diego

2016-03-04

The ability to control and modulate the action potential firing in neurons represents a powerful tool for neuroscience research and clinical applications. While neuronal excitation has been achieved with many tools, including electrical and optical stimulation, hyperpolarization and neuronal inhibition are typically obtained through patch-clamp or optogenetic manipulations. Here we report the use of conjugated polymer films interfaced with neurons for inducing a light-mediated inhibition of their electrical activity. We show that prolonged illumination of the interface triggers a sustained hyperpolarization of the neuronal membrane that significantly reduces both spontaneous and evoked action potential firing. We demonstrate that the polymeric interface can be activated by either visible or infrared light and is capable of modulating neuronal activity in brain slices and explanted retinas. These findings prove the ability of conjugated polymers to tune neuronal firing and suggest their potential application for the in-vivo modulation of neuronal activity.

Light-evoked hyperpolarization and silencing of neurons by conjugated polymers

PubMed Central

Feyen, Paul; Colombo, Elisabetta; Endeman, Duco; Nova, Mattia; Laudato, Lucia; Martino, Nicola; Antognazza, Maria Rosa; Lanzani, Guglielmo; Benfenati, Fabio; Ghezzi, Diego

2016-01-01

The ability to control and modulate the action potential firing in neurons represents a powerful tool for neuroscience research and clinical applications. While neuronal excitation has been achieved with many tools, including electrical and optical stimulation, hyperpolarization and neuronal inhibition are typically obtained through patch-clamp or optogenetic manipulations. Here we report the use of conjugated polymer films interfaced with neurons for inducing a light-mediated inhibition of their electrical activity. We show that prolonged illumination of the interface triggers a sustained hyperpolarization of the neuronal membrane that significantly reduces both spontaneous and evoked action potential firing. We demonstrate that the polymeric interface can be activated by either visible or infrared light and is capable of modulating neuronal activity in brain slices and explanted retinas. These findings prove the ability of conjugated polymers to tune neuronal firing and suggest their potential application for the in-vivo modulation of neuronal activity. PMID:26940513

Action Potentials Initiate in the Axon Initial Segment and Propagate Through Axon Collaterals Reliably in Cerebellar Purkinje Neurons

PubMed Central

Foust, Amanda; Popovic, Marko; Zecevic, Dejan; McCormick, David A.

2010-01-01

Purkinje neurons are the output cells of the cerebellar cortex and generate spikes in two distinct modes, known as simple and complex spikes. Revealing the point of origin of these action potentials, and how they conduct into local axon collaterals, is important for understanding local and distal neuronal processing and communication. By utilizing a recent improvement in voltage sensitive dye imaging technique that provided exceptional spatial and temporal resolution, we were able to resolve the region of spike initiation as well as follow spike propagation into axon collaterals for each action potential initiated on single trials. All fast action potentials, for both simple and complex spikes, whether occurring spontaneously or in response to a somatic current pulse or synaptic input, initiated in the axon initial segment. At discharge frequencies of less than approximately 250 Hz, spikes propagated faithfully through the axon and axon collaterals, in a saltatory manner. Propagation failures were only observed for very high frequencies or for the spikelets associated with complex spikes. These results demonstrate that the axon initial segment is a critical decision point in Purkinje cell processing and that the properties of axon branch points are adjusted to maintain faithful transmission. PMID:20484631

Irregular spiking of pyramidal neurons organizes as scale-invariant neuronal avalanches in the awake state

PubMed Central

Bellay, Timothy; Klaus, Andreas; Seshadri, Saurav; Plenz, Dietmar

2015-01-01

Spontaneous fluctuations in neuronal activity emerge at many spatial and temporal scales in cortex. Population measures found these fluctuations to organize as scale-invariant neuronal avalanches, suggesting cortical dynamics to be critical. Macroscopic dynamics, though, depend on physiological states and are ambiguous as to their cellular composition, spatiotemporal origin, and contributions from synaptic input or action potential (AP) output. Here, we study spontaneous firing in pyramidal neurons (PNs) from rat superficial cortical layers in vivo and in vitro using 2-photon imaging. As the animal transitions from the anesthetized to awake state, spontaneous single neuron firing increases in irregularity and assembles into scale-invariant avalanches at the group level. In vitro spike avalanches emerged naturally yet required balanced excitation and inhibition. This demonstrates that neuronal avalanches are linked to the global physiological state of wakefulness and that cortical resting activity organizes as avalanches from firing of local PN groups to global population activity. DOI: http://dx.doi.org/10.7554/eLife.07224.001 PMID:26151674

Role of the Axon Initial Segment in the Control of Spontaneous Frequency of Nigral Dopaminergic Neurons In Vivo.

PubMed

Meza, Rodrigo C; López-Jury, Luciana; Canavier, Carmen C; Henny, Pablo

2018-01-17

The spontaneous tonic discharge activity of nigral dopamine neurons plays a fundamental role in dopaminergic signaling. To investigate the role of neuronal morphology and architecture with respect to spontaneous activity in this population, we visualized the 3D structure of the axon initial segment (AIS) along with the entire somatodendritic domain of adult male mouse dopaminergic neurons, previously recorded in vivo We observed a positive correlation of the firing rate with both proximity and size of the AIS. Computational modeling showed that the size of the AIS, but not its position within the somatodendritic domain, is the major causal determinant of the tonic firing rate in the intact model, by virtue of the higher intrinsic frequency of the isolated AIS. Further mechanistic analysis of the relationship between neuronal morphology and firing rate showed that dopaminergic neurons function as a coupled oscillator whose frequency of discharge results from a compromise between AIS and somatodendritic oscillators. Thus, morphology plays a critical role in setting the basal tonic firing rate, which in turn could control striatal dopaminergic signaling that mediates motivation and movement. SIGNIFICANCE STATEMENT The frequency at which nigral dopamine neurons discharge action potentials sets baseline dopamine levels in the brain, which enables activity in motor, cognitive, and motivational systems. Here, we demonstrate that the size of the axon initial segment, a subcellular compartment responsible for initiating action potentials, is a key determinant of the firing rate in these neurons. The axon initial segment and all the molecular components that underlie its critical function may provide a novel target for the regulation of dopamine levels in the brain. Copyright © 2018 the authors 0270-6474/18/380733-12$15.00/0.

Enhanced GABAergic Inputs Contribute to Functional Alterations of Cholinergic Interneurons in the R6/2 Mouse Model of Huntington's Disease.

PubMed

Holley, Sandra M; Joshi, Prasad R; Parievsky, Anna; Galvan, Laurie; Chen, Jane Y; Fisher, Yvette E; Huynh, My N; Cepeda, Carlos; Levine, Michael S

2015-01-01

In Huntington's disease (HD), a hereditary neurodegenerative disorder, striatal medium-sized spiny neurons undergo degenerative changes. In contrast, large cholinergic interneurons (LCIs) are relatively spared. However, their ability to release acetylcholine (ACh) is impaired. The present experiments examined morphological and electrophysiological properties of LCIs in the R6/2 mouse model of HD. R6/2 mice show a severe, rapidly progressing phenotype. Immunocytochemical analysis of choline acetyltransferase-positive striatal neurons showed that, although the total number of cells was not changed, somatic areas were significantly smaller in symptomatic R6/2 mice compared to wildtype (WT) littermates, For electrophysiology, brain slices were obtained from presymptomatic (3-4 weeks) and symptomatic (>8 weeks) R6/2 mice and their WT littermates. Striatal LCIs were identified by somatic size and spontaneous action potential firing in the cell-attached mode. Passive and active membrane properties of LCIs were similar in presymptomatic R6/2 and WT mice. In contrast, LCIs from symptomatic R6/2 animals displayed smaller membrane capacitance and higher input resistance, consistent with reduced somatic size. In addition, more LCIs from symptomatic mice displayed irregular firing patterns and bursts of action potentials. They also displayed a higher frequency of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) and larger amplitude of electrically evoked IPSCs. Selective optogenetic stimulation of somatostatin- but not parvalbumin-containing interneurons also evoked larger amplitude IPSCs in LCIs from R6/2 mice. In contrast, glutamatergic spontaneous or evoked postsynaptic currents were not affected. Morphological and electrophysiological alterations, in conjunction with the presence of mutant huntingtin in LCIs, could explain impaired ACh release in HD mouse models.

Inhibitory effects of sevoflurane on pacemaking activity of sinoatrial node cells in guinea-pig heart

PubMed Central

Kojima, Akiko; Kitagawa, Hirotoshi; Omatsu-Kanbe, Mariko; Matsuura, Hiroshi; Nosaka, Shuichi

2012-01-01

BACKGROUND AND PURPOSE The volatile anaesthetic sevoflurane affects heart rate in clinical settings. The present study investigated the effect of sevoflurane on sinoatrial (SA) node automaticity and its underlying ionic mechanisms. EXPERIMENTAL APPROACH Spontaneous action potentials and four ionic currents fundamental for pacemaking, namely, the hyperpolarization-activated cation current (If), T-type and L-type Ca2+ currents (ICa,T and ICa,L, respectively), and slowly activating delayed rectifier K+ current (IKs), were recorded in isolated guinea-pig SA node cells using perforated and conventional whole-cell patch-clamp techniques. Heart rate in guinea-pigs was recorded ex vivo in Langendorff mode and in vivo during sevoflurane inhalation. KEY RESULTS In isolated SA node cells, sevoflurane (0.12–0.71 mM) reduced the firing rate of spontaneous action potentials and its electrical basis, diastolic depolarization rate, in a qualitatively similar concentration-dependent manner. Sevoflurane (0.44 mM) reduced spontaneous firing rate by approximately 25% and decreased If, ICa,T, ICa,L and IKs by 14.4, 31.3, 30.3 and 37.1%, respectively, without significantly affecting voltage dependence of current activation. The negative chronotropic effect of sevoflurane was partly reproduced by a computer simulation of SA node cell electrophysiology. Sevoflurane reduced heart rate in Langendorff-perfused hearts, but not in vivo during sevoflurane inhalation in guinea-pigs. CONCLUSIONS AND IMPLICATIONS Sevoflurane at clinically relevant concentrations slowed diastolic depolarization and thereby reduced pacemaking activity in SA node cells, at least partly due to its inhibitory effect on If, ICa,T and ICa,L. These findings provide an important electrophysiological basis of alterations in heart rate during sevoflurane anaesthesia in clinical settings. PMID:22356456

The neural basis of the imitation drive.

PubMed

Hanawa, Sugiko; Sugiura, Motoaki; Nozawa, Takayuki; Kotozaki, Yuka; Yomogida, Yukihito; Ihara, Mizuki; Akimoto, Yoritaka; Thyreau, Benjamin; Izumi, Shinichi; Kawashima, Ryuta

2016-01-01

Spontaneous imitation is assumed to underlie the acquisition of important skills by infants, including language and social interaction. In this study, functional magnetic resonance imaging (fMRI) was used to examine the neural basis of 'spontaneously' driven imitation, which has not yet been fully investigated. Healthy participants were presented with movie clips of meaningless bimanual actions and instructed to observe and imitate them during an fMRI scan. The participants were subsequently shown the movie clips again and asked to evaluate the strength of their 'urge to imitate' (Urge) for each action. We searched for cortical areas where the degree of activation positively correlated with Urge scores; significant positive correlations were observed in the right supplementary motor area (SMA) and bilateral midcingulate cortex (MCC) under the imitation condition. These areas were not explained by explicit reasons for imitation or the kinematic characteristics of the actions. Previous studies performed in monkeys and humans have implicated the SMA and MCC/caudal cingulate zone in voluntary actions. This study also confirmed the functional connectivity between Urge and imitation performance using a psychophysiological interaction analysis. Thus, our findings reveal the critical neural components that underlie spontaneous imitation and provide possible reasons why infants imitate spontaneously. © The Author (2015). Published by Oxford University Press.

Effect of Mucuna pruriens Seed Extract Pretreatment on the Responses of Spontaneously Beating Rat Atria and Aortic Ring to Naja sputatrix (Javan Spitting Cobra) Venom

PubMed Central

Fung, Shin Yee; Tan, Nget Hong; Sim, Si Mui; Aguiyi, John C.

2012-01-01

Mucuna pruriens Linn. (velvet bean) has been used by native Nigerians as a prophylactic for snakebite. Rats pretreated with M. pruriens seed extract (MPE) have been shown to protect against the lethal and cardiovascular depressant effects of Naja sputatrix (Javan spitting cobra) venoms, and the protective effect involved immunological neutralization of the venom toxins. To investigate further the mechanism of the protective effect of MPE pretreatment against cobra venom toxicity, the actions of Naja sputatrix venom on spontaneously beating rat atria and aortic rings isolated from both MPE pretreated and untreated rats were studied. Our results showed that the MPE pretreatment conferred protection against cobra venom-induced depression of atrial contractility and atrial rate in the isolated atrial preparations, but it had no effect on the venom-induced contractile response of aortic ring preparation. These observations suggested that the protective effect of MPE pretreatment against cobra venom toxicity involves a direct protective action of MPE on the heart function, in addition to the known immunological neutralization mechanism, and that the protective effect does not involve action on blood vessel contraction. The results also suggest that M. pruriens seed may contain novel cardioprotective agent with potential therapeutic value. PMID:21785646

On-chip, multisite extracellular and intracellular recordings from primary cultured skeletal myotubes

PubMed Central

Rabieh, Noha; Ojovan, Silviya M.; Shmoel, Nava; Erez, Hadas; Maydan, Eilon; Spira, Micha E.

2016-01-01

In contrast to the extensive use of microelectrode array (MEA) technology in electrophysiological studies of cultured neurons and cardiac muscles, the vast field of skeletal muscle research has yet to adopt the technology. Here we demonstrate an empowering MEA technology for high quality, multisite, long-term electrophysiological recordings from cultured skeletal myotubes. Individual rat skeletal myotubes cultured on micrometer sized gold mushroom-shaped microelectrode (gMμE) based MEA tightly engulf the gMμEs, forming a high seal resistance between the myotubes and the gMμEs. As a consequence, spontaneous action potentials generated by the contracting myotubes are recorded as extracellular field potentials with amplitudes of up to 10 mV for over 14 days. Application of a 10 ms, 0.5–0.9 V voltage pulse through the gMμEs electroporated the myotube membrane, and transiently converted the extracellular to intracellular recording mode for 10–30 min. In a fraction of the cultures stable attenuated intracellular recordings were spontaneously produced. In these cases or after electroporation, subthreshold spontaneous potentials were also recorded. The introduction of the gMμE-MEA as a simple-to-use, high-quality electrophysiological tool together with the progress made in the use of cultured human myotubes opens up new venues for basic and clinical skeletal muscle research, preclinical drug screening, and personalized medicine. PMID:27812002

Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential

PubMed Central

Capel, Rebecca A.; Herring, Neil; Kalla, Manish; Yavari, Arash; Mirams, Gary R.; Douglas, Gillian; Bub, Gil; Channon, Keith; Paterson, David J.; Terrar, Derek A.; Burton, Rebecca-Ann B.

2015-01-01

Background Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption. Objectives The purpose of this study was to investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia. Methods We assessed the effects of HCQ on (1) cardiac beating rate in vitro (mice); (2) the “funny” current (If) in isolated guinea pig sinoatrial node (SAN) myocytes (1, 3, 10 µM); (3) heart rate and blood pressure in vivo by acute bolus injection (rat, dose range 1–30 mg/kg), (4) blood pressure and ventricular function during feeding (mouse, 100 mg/kg/d for 2 wk, tail cuff plethysmography, anesthetized echocardiography). Results In mouse atria, spontaneous beating rate was significantly (P < .05) reduced (by 9% ± 3% and 15% ± 2% at 3 and 10 µM HCQ, n = 7). In guinea pig isolated SAN cells, HCQ conferred a significant reduction in spontaneous action potential firing rate (17% ± 6%, 1 μM dose) and a dose-dependent reduction in If (13% ± 3% at 1 µM; 19% ± 2% at 3 µM). Effects were also observed on L-type calcium ion current (ICaL) (12% ± 4% reduction) and rapid delayed rectifier potassium current (IKr) (35% ± 4%) at 3 µM. Intravenous HCQ decreased heart rate in anesthetized rats (14.3% ± 1.1% at 15mg/kg; n = 6) without significantly reducing mean arterial blood pressure. In vivo feeding studies in mice showed no significant change in systolic blood pressure nor left ventricular function. Conclusions We have shown that HCQ acts as a bradycardic agent in SAN cells, in atrial preparations, and in vivo. HCQ slows the rate of spontaneous action potential firing in the SAN through multichannel inhibition, including that of If. PMID:26025323

Human adipose tissue-derived stem cells exhibit proliferation potential and spontaneous rhythmic contraction after fusion with neonatal rat cardiomyocytes.

PubMed

Metzele, Roxana; Alt, Christopher; Bai, Xiaowen; Yan, Yasheng; Zhang, Zhi; Pan, Zhizhong; Coleman, Michael; Vykoukal, Jody; Song, Yao-Hua; Alt, Eckhard

2011-03-01

Various types of stem cells have been shown to have beneficial effects on cardiac function. It is still debated whether fusion of injected stem cells with local resident cardiomyocytes is one of the mechanisms. To better understand the role of fusion in stem cell-based myocardial regeneration, the present study was designed to investigate the fate of human adipose tissue-derived stem cells (hASCs) fused with neonatal rat cardiomyocytes in vitro. hASCs labeled with the green fluorescent probe Vybrant DiO were cocultured with neonatal rat cardiomyocytes labeled with the red fluorescent probe Vybrant DiI and then treated with fusion-inducing hemagglutinating virus of Japan (HVJ). Cells that incorporated both red and green fluorescent signals were considered to be hASCs that had fused with rat cardiomyocytes. Fusion efficiency was 19.86 ± 4.84% at 5 d after treatment with HVJ. Most fused cells displayed cardiomyocyte-like morphology and exhibited spontaneous rhythmic contraction. Both immunofluorescence staining and lentiviral vector labeling showed that fused cells contained separate rat cardiomyocyte and hASC nuclei. Immunofluorescence staining assays demonstrated that human nuclei in fused cells still expressed the proliferation marker Ki67. In addition, hASCs fused with rat cardiomyocytes were positive for troponin I. Whole-cell voltage-clamp analysis demonstrated action potentials in beating fused cells. RT-PCR analysis using rat- or human-specific myosin heavy chain primers revealed that the myosin heavy-chain expression in fused cells was derived from rat cardiomyocytes. Real-time PCR identified expression of human troponin T in fused cells and the presence of rat cardiomyocytes induced a cardiomyogenic protein expression of troponin T in human ASCs. This study illustrates that hASCs exhibit both stem cell (proliferation) and cardiomyocyte properties (action potential and spontaneous rhythmic beating) after fusion with rat cardiomyocytes, supporting the theory that fusion, even if artificially induced in our study, could indeed be a mechanism for cardiomyocyte renewal in the heart.

Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential.

PubMed

Capel, Rebecca A; Herring, Neil; Kalla, Manish; Yavari, Arash; Mirams, Gary R; Douglas, Gillian; Bub, Gil; Channon, Keith; Paterson, David J; Terrar, Derek A; Burton, Rebecca-Ann B

2015-10-01

Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption. The purpose of this study was to investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia. We assessed the effects of HCQ on (1) cardiac beating rate in vitro (mice); (2) the "funny" current (If) in isolated guinea pig sinoatrial node (SAN) myocytes (1, 3, 10 µM); (3) heart rate and blood pressure in vivo by acute bolus injection (rat, dose range 1-30 mg/kg), (4) blood pressure and ventricular function during feeding (mouse, 100 mg/kg/d for 2 wk, tail cuff plethysmography, anesthetized echocardiography). In mouse atria, spontaneous beating rate was significantly (P < .05) reduced (by 9% ± 3% and 15% ± 2% at 3 and 10 µM HCQ, n = 7). In guinea pig isolated SAN cells, HCQ conferred a significant reduction in spontaneous action potential firing rate (17% ± 6%, 1 μM dose) and a dose-dependent reduction in If (13% ± 3% at 1 µM; 19% ± 2% at 3 µM). Effects were also observed on L-type calcium ion current (ICaL) (12% ± 4% reduction) and rapid delayed rectifier potassium current (IKr) (35% ± 4%) at 3 µM. Intravenous HCQ decreased heart rate in anesthetized rats (14.3% ± 1.1% at 15mg/kg; n = 6) without significantly reducing mean arterial blood pressure. In vivo feeding studies in mice showed no significant change in systolic blood pressure nor left ventricular function. We have shown that HCQ acts as a bradycardic agent in SAN cells, in atrial preparations, and in vivo. HCQ slows the rate of spontaneous action potential firing in the SAN through multichannel inhibition, including that of If. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Osmotic and Salt Stresses Modulate Spontaneous and Glutamate-Induced Action Potentials and Distinguish between Growth and Circumnutation in Helianthus annuus Seedlings

PubMed Central

Stolarz, Maria; Dziubinska, Halina

2017-01-01

Action potentials (APs), i.e., long-distance electrical signals, and circumnutations (CN), i.e., endogenous plant organ movements, are shaped by ion fluxes and content in excitable and motor tissues. The appearance of APs and CN as well as growth parameters in seedlings and 3-week old plants of Helianthus annuus treated with osmotic and salt stress (0–500 mOsm) were studied. Time-lapse photography and extracellular measurements of electrical potential changes were performed. The hypocotyl length was strongly reduced by the osmotic and salt stress. CN intensity declined due to the osmotic but not salt stress. The period of CN in mild salt stress was similar to the control (~164 min) and increased to more than 200 min in osmotic stress. In sunflower seedlings growing in a hydroponic medium, spontaneous APs (SAPs) propagating basipetally and acropetally with a velocity of 12–20 cm min−1 were observed. The number of SAPs increased 2–3 times (7–10 SAPs 24 h−1plant−1) in the mild salt stress (160 mOsm NaCl and KCl), compared to the control and strong salt stress (3–4 SAPs 24 h−1 plant−1 in the control and 300 mOsm KCl and NaCl). Glutamate-induced series of APs were inhibited in the strong salt stress-treated seedlings but not at the mild salt stress and osmotic stress. Additionally, in 3-week old plants, the injection of the hypo- or hyperosmotic solution at the base of the sunflower stem evoked series of APs (3–24 APs) transmitted along the stem. It has been shown that osmotic and salt stresses modulate differently hypocotyl growth and CN and have an effect on spontaneous and evoked APs in sunflower seedlings. We suggested that potassium, sodium, and chloride ions at stress concentrations in the nutrient medium modulate sunflower excitability and CN. PMID:29093722

Using cholinergic M1 receptor positive allosteric modulators to improve memory via enhancement of brain cholinergic communication.

PubMed

Chambon, Caroline; Jatzke, Claudia; Wegener, Nico; Gravius, Andreas; Danysz, Wojciech

2012-12-15

Benzylquinolone carboxylic acid (BQCA) is a recently described cholinergic muscarinic M(1) receptor positive allosteric modulator having potential as cognitive enhancer in dementia. The present study focused on the characterisation of BQCA's mode of action in relation to positive effects on memory and side-effects in an animal model. To get insight into this mode of action, in vitro receptor potency/left shift experiments in cells stably expressing the rat's M(1) receptor were performed. They revealed an inflection point value of BQCA corresponding to 306nM, and potentiation of the agonist response up to 47-fold in presence of 10μM of BQCA. In vivo, brain microdialysis showed a maximal brain level of 270nM, 40min after i.p. administration at 10mg/kg. Based on in vitro data obtained with this dose, it can be concluded that BQCA reaches brain levels which should potentiate the agonist response about 4-fold. Behavioural data confirmed that BQCA used at 10mg/kg attenuated scopolamine-induced memory deficit in a spontaneous alternation task. Moreover, BQCA showed no side effect at 10mg/kg and above in spontaneous locomotion and salivation tests. The profile of BQCA observed in the present study displays a clear advantage over the M(1)-M(3) agonist cevimeline. The present data show the therapeutic potential of the M(1) receptor positive allosteric modulator BQCA for the treatment of memory deficits observed in Alzheimer's disease. Copyright © 2012. Published by Elsevier B.V.

Optophysiological Approach to Resolve Neuronal Action Potentials with High Spatial and Temporal Resolution in Cultured Neurons

PubMed Central

Pagès, Stéphane; Côté, Daniel; De Koninck, Paul

2011-01-01

Cell to cell communication in the central nervous system is encoded into transient and local membrane potential changes (ΔVm). Deciphering the rules that govern synaptic transmission and plasticity entails to be able to perform Vm recordings throughout the entire neuronal arborization. Classical electrophysiology is, in most cases, not able to do so within small and fragile neuronal subcompartments. Thus, optical techniques based on the use of fluorescent voltage-sensitive dyes (VSDs) have been developed. However, reporting spontaneous or small ΔVm from neuronal ramifications has been challenging, in part due to the limited sensitivity and phototoxicity of VSD-based optical measurements. Here we demonstrate the use of water soluble VSD, ANNINE-6plus, with laser-scanning microscopy to optically record ΔVm in cultured neurons. We show that the sensitivity (>10% of fluorescence change for 100 mV depolarization) and time response (sub millisecond) of the dye allows the robust detection of action potentials (APs) even without averaging, allowing the measurement of spontaneous neuronal firing patterns. In addition, we show that back-propagating APs can be recorded, along distinct dendritic sites and within dendritic spines. Importantly, our approach does not induce any detectable phototoxic effect on cultured neurons. This optophysiological approach provides a simple, minimally invasive, and versatile optical method to measure electrical activity in cultured neurons with high temporal (ms) resolution and high spatial (μm) resolution. PMID:22016723

Electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure.

PubMed

Fan, Ling; Chen, Li-Feng; Fan, Jing

2017-12-01

To investigate the electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure. Guinea pigs model of iron deficiency anemia complicated with chronic heart failure in 10 guinea pigs of the experimental group was made by feeding a low iron diet, pure water and subcutaneous injection of isoproterenol. The control group consisting of 11 guinea pigs was given normal food, normal water and injected with normal saline. The left ventricular outflow tract model specimen was also prepared. The standard microelectrode technique was used to observe electrophysiological changes of autonomic cells in the outflow tract of left ventricular heart failure complicated with iron deficiency anemia in guinea pig model. The indicators of observation were maximal diastolic potential, action potential amplitude, 0 phase maximal depolarization velocity, 4 phase automatic depolarization velocity, repolarization 50% and 90%, and spontaneous discharge frequency. Compared with the control group, 4 phase automatic depolarization velocity, spontaneous discharge frequency and 0 phase maximal depolarization velocity decreased significantly (P < 0.01) and action potential amplitude reduced (P < 0.01) in model group. Moreover, repolarization 50% and 90% increased (P < 0.01). There are electrophysiological abnormalities of the left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with heart failure. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Nail-biting stuff? The effect of N-acetyl cysteine on nail-biting.

PubMed

Berk, Michael; Jeavons, Sue; Dean, Olivia M; Dodd, Seetal; Moss, Kirsteen; Gama, Clarissa S; Malhi, Gin S

2009-07-01

N-acetyl cysteine (NAC) is a widely available nutraceutical with a variety of actions. As a precursor of cysteine and glutathione, it has antioxidant properties that may impact on mood and contribute to an effect on impulsivity and obsessive behaviour. Via its additional effect on glutamate via the cystine-glutamate exchange system, NAC has been shown to mediate impulsivity in preclinical models of addiction, reduce craving, and cue extinction. Further, by boosting glutathione, NAC acts as a potent antioxidant and has been shown in two positive, large-scale randomized placebo-controlled trials to affect negative symptoms in schizophrenia and depression in bipolar disorder. We describe three cases in which its actions specifically on nail-biting and associated anxiety may offer a potential treatment. The spontaneous findings are reported as part of an ongoing treatment trial examining the utility of NAC in bipolar disorder. Its actions, if robustly replicated, also point to potential treatment targets in glutathione or glutamate pathways in the brain.

Vision Drives Correlated Activity without Patterned Spontaneous Activity in Developing Xenopus Retina

PubMed Central

Demas, James A.; Payne, Hannah; Cline, Hollis T.

2011-01-01

Developing amphibians need vision to avoid predators and locate food before visual system circuits fully mature. Xenopus tadpoles can respond to visual stimuli as soon as retinal ganglion cells (RGCs) innervate the brain, however, in mammals, chicks and turtles, RGCs reach their central targets many days, or even weeks, before their retinas are capable of vision. In the absence of vision, activity-dependent refinement in these amniote species is mediated by waves of spontaneous activity that periodically spread across the retina, correlating the firing of action potentials in neighboring RGCs. Theory suggests that retinorecipient neurons in the brain use patterned RGC activity to sharpen the retinotopy first established by genetic cues. We find that in both wild type and albino Xenopus tadpoles, RGCs are spontaneously active at all stages of tadpole development studied, but their population activity never coalesces into waves. Even at the earliest stages recorded, visual stimulation dominates over spontaneous activity and can generate patterns of RGC activity similar to the locally correlated spontaneous activity observed in amniotes. In addition, we show that blocking AMPA and NMDA type glutamate receptors significantly decreases spontaneous activity in young Xenopus retina, but that blocking GABAA receptor blockers does not. Our findings indicate that vision drives correlated activity required for topographic map formation. They further suggest that developing retinal circuits in the two major subdivisions of tetrapods, amphibians and amniotes, evolved different strategies to supply appropriately patterned RGC activity to drive visual circuit refinement. PMID:21312343

Turning Virtual Reality into Reality: A Checklist to Ensure Virtual Reality Studies of Eating Behavior and Physical Activity Parallel the Real World

PubMed Central

Tal, Aner; Wansink, Brian

2011-01-01

Virtual reality (VR) provides a potentially powerful tool for researchers seeking to investigate eating and physical activity. Some unique conditions are necessary to ensure that the psychological processes that influence real eating behavior also influence behavior in VR environments. Accounting for these conditions is critical if VR-assisted research is to accurately reflect real-world situations. The current work discusses key considerations VR researchers must take into account to ensure similar psychological functioning in virtual and actual reality and does so by focusing on the process of spontaneous mental simulation. Spontaneous mental simulation is prevalent under real-world conditions but may be absent under VR conditions, potentially leading to differences in judgment and behavior between virtual and actual reality. For simulation to occur, the virtual environment must be perceived as being available for action. A useful chart is supplied as a reference to help researchers to investigate eating and physical activity more effectively. PMID:21527088

Turning virtual reality into reality: a checklist to ensure virtual reality studies of eating behavior and physical activity parallel the real world.

PubMed

Tal, Aner; Wansink, Brian

2011-03-01

Virtual reality (VR) provides a potentially powerful tool for researchers seeking to investigate eating and physical activity. Some unique conditions are necessary to ensure that the psychological processes that influence real eating behavior also influence behavior in VR environments. Accounting for these conditions is critical if VR-assisted research is to accurately reflect real-world situations. The current work discusses key considerations VR researchers must take into account to ensure similar psychological functioning in virtual and actual reality and does so by focusing on the process of spontaneous mental simulation. Spontaneous mental simulation is prevalent under real-world conditions but may be absent under VR conditions, potentially leading to differences in judgment and behavior between virtual and actual reality. For simulation to occur, the virtual environment must be perceived as being available for action. A useful chart is supplied as a reference to help researchers to investigate eating and physical activity more effectively. © 2011 Diabetes Technology Society.

Voltage-gated currents in identified rat olfactory receptor neurons.

PubMed

Trombley, P Q; Westbrook, G L

1991-02-01

Whole-cell recording techniques were used to characterize voltage-gated membrane currents in neonatal rat olfactory receptor neurons (ORNs) in cell culture. Mature ORNs were identified in culture by their characteristic bipolar morphology, by retrograde labeling techniques, and by olfactory marker protein (OMP) immunoreactivity. ORNs did not have spontaneous activity, but fired action potentials to depolarizing current pulses. Action potentials were blocked by tetrodotoxin (TTX), which contrasts with the TTX-resistant action potentials in salamander olfactory receptor cells (e.g., Firestein and Werblin, 1987). Prolonged, suprathreshold current pulses evoked only a single action potential; however, repetitive firing up to 35 Hz could be elicited by a series of brief depolarizing pulses. Under voltage clamp, the TTX-sensitive sodium current had activation and inactivation properties similar to other excitable cells. In TTX and 20 mM barium, sustained inward current were evoked by voltage steps positive to -30 mV. This current was blocked by Cd (100 microM) and by nifedipine (IC50 = 368 nM) consistent with L-type calcium channels in other neurons. No T-type calcium current was observed. Voltage steps positive to -20 mV also evoked an outward current that did not inactivate during 100-msec depolarizations. Tail current analysis of this current was consistent with a selective potassium conductance. The outward current was blocked by external tetraethylammonium but was unaffected by Cd or 4-aminopyridine (4-AP) or by removal of external calcium. A transient outward current was not observed. The 3 voltage-dependent conductances in cultured rat ORNs appear to be sufficient for 2 essential functions: action potential generation and transmitter release. As a single odorant-activated channel can trigger an action potential (e.g., Lynch and Barry, 1989), the repetitive firing seen with brief depolarizing pulses suggests that ORNs do not integrate sensory input, but rather act as high-fidelity relays such that each opening of an odorant-activated channel reaches the olfactory bulb glomeruli as an action potential.

Actions of brain-derived neurotrophic factor on evoked and spontaneous EPSCs dissociate with maturation of neurones cultured from rat visual cortex

PubMed Central

Taniguchi, Nobuaki; Takada, Naoki; Kimura, Fumitaka; Tsumoto, Tadaharu

2000-01-01

To address the question of whether brain-derived neurotrophic factor (BDNF) directly enhances excitatory synaptic transmission, we recorded excitatory postsynaptic currents (EPSCs) from solitary neurones cultured on glial microislands for 7–38 days, and observed changes in EPSCs after the application of BDNF. In this preparation the possible action of BDNF on GABAergic inhibition was not involved, and evoked and spontaneous (miniature) EPSCs were derived from the same group of synapses (autapses). The application of BDNF at a concentration of 200 ng ml−1 rapidly enhanced the frequency of miniature EPSCs (mEPSCs) in almost all the neurones tested. On the other hand, the amplitude of mEPSCs did not change at all, suggesting that the site of BDNF action is presynaptic. In contrast to the enhanced frequency of mEPSCs, evoked EPSCs were not potentiated in 61 % of the cells tested. Most of these BDNF-insensitive EPSCs had a peak amplitude larger than 1 nA, while most of the other BDNF-sensitive EPSCs had a smaller amplitude. The former EPSCs had smaller coefficients of variation (CVs) of amplitude, while the latter had larger CVs, suggesting the possibility that the presynaptic release probability for the former groups of EPSCs might have beeen saturated so that the BDNF action was occluded. To test this possibility we applied a low Ca2+ solution to 17 cells and reduced the amplitude of their evoked EPSCs to less than or near to 1 nA. It was found, however, that BDNF did not enhance these EPSCs. Rather, evoked EPSCs of almost all the cells cultured for less than 15 days were enhanced by BDNF, while those of most of the cells cultured for longer than 16 days were not enhanced. These results suggest that BDNF enhances transmitter release from presynaptic sites through its action on the release machinery, which can be differentiated into a BDNF-insensitive form for evoked release and a BDNF-sensitive form for spontaneous release with maturation of synapses. PMID:10990542

Reduction in spontaneous firing of mouse excitatory layer 4 cortical neurons following visual classical conditioning

NASA Astrophysics Data System (ADS)

Bekisz, Marek; Shendye, Ninad; Raciborska, Ida; Wróbel, Andrzej; Waleszczyk, Wioletta J.

2017-08-01

The process of learning induces plastic changes in neuronal network of the brain. Our earlier studies on mice showed that classical conditioning in which monocular visual stimulation was paired with an electric shock to the tail enhanced GABA immunoreactivity within layer 4 of the monocular part of the primary visual cortex (V1), contralaterally to the stimulated eye. In the present experiment we investigated whether the same classical conditioning paradigm induces changes of neuronal excitability in this cortical area. Two experimental groups were used: mice that underwent 7-day visual classical conditioning and controls. Patch-clamp whole-cell recordings were performed from ex vivo slices of mouse V1. The slices were perfused with the modified artificial cerebrospinal fluid, the composition of which better mimics the brain interstitial fluid in situ and induces spontaneous activity. The neuronal excitability was characterized by measuring the frequency of spontaneous action potentials. We found that layer 4 star pyramidal cells located in the monocular representation of the "trained" eye in V1 had lower frequency of spontaneous activity in comparison with neurons from the same cortical region of control animals. Weaker spontaneous firing indicates decreased general excitability of star pyramidal neurons within layer 4 of the monocular representation of the "trained" eye in V1. Such effect could result from enhanced inhibitory processes accompanying learning in this cortical area.

Caffeine depression of spontaneous activity in rabbit sino-atrial node cells.

PubMed

Satoh, H

1993-05-01

1. Effects of caffeine on the action potentials and the membrane currents in spontaneously beating rabbit sino-atrial (SA) node cells were examined using a two-microelectrode technique. 2. Cumulative administrations of caffeine (1-10 mM) caused a negative chronotropic effect in a concentration-dependent manner, which was not modified by atropine (0.1 microM). At 10 mM, caffeine increased the amplitude and prolonged the duration of action potentials significantly; the other parameters were unaffected. 3. In 3 of 16 preparations, caffeine (5 mM) elicited arrhythmia. At high Ca2+ (8.1 mM), caffeine (5 mM) increased the incidence of arrhythmia. 4. Caffeine (0.5-10 mM) enhanced the slow inward current, but at 10 mM decreased the enhanced peak current by 5 mM. The hyperpolarization-activated inward current was also enhanced by caffeine, but 10 mM caffeine decreased the current peak as compared with that at 5 mM. In addition, caffeine inhibited the delayed rectifying outward current in a concentration-dependent manner, accompanied by a depressed activation curve without any shift in the half-maximum activation voltage. 5. Caffeine elevated the cytoplasmic Ca2+ level in the SA node cells loaded with Ca(2+)-sensitive fluorescent dye (fura-2). 6. These results suggest that caffeine enhances and/or inhibits the ionic currents and elicits arrhythmia due to the induction of cellular calcium overload.

Myelin Loss and Axonal Ion Channel Adaptations Associated with Gray Matter Neuronal Hyperexcitability

PubMed Central

Hamada, Mustafa S.

2015-01-01

Myelination and voltage-gated ion channel clustering at the nodes of Ranvier are essential for the rapid saltatory conduction of action potentials. Whether myelination influences the structural organization of the axon initial segment (AIS) and action potential initiation is poorly understood. Using the cuprizone mouse model, we combined electrophysiological recordings with immunofluorescence of the voltage-gated Nav1.6 and Kv7.3 subunits and anchoring proteins to analyze the functional and structural properties of single demyelinated neocortical L5 axons. Whole-cell recordings demonstrated that neurons with demyelinated axons were intrinsically more excitable, characterized by increased spontaneous suprathreshold depolarizations as well as antidromically propagating action potentials ectopically generated in distal parts of the axon. Immunofluorescence examination of demyelinated axons showed that βIV-spectrin, Nav1.6, and the Kv7.3 channels in nodes of Ranvier either dissolved or extended into the paranodal domains. In contrast, while the AIS in demyelinated axons started more closely to the soma, ankyrin G, βIV-spectrin, and the ion channel expression were maintained. Structure–function analysis and computational modeling, constrained by the AIS location and realistic dendritic and axonal morphologies, confirmed that a more proximal onset of the AIS slightly reduced the efficacy of action potential generation, suggesting a compensatory role. These results suggest that oligodendroglial myelination is not only important for maximizing conduction velocity, but also for limiting hyperexcitability of pyramidal neurons. PMID:25948275

A store-operated current (SOC) mediates oxytocin autocontrol in the developing rat hypothalamus.

PubMed

Tobin, Vicky; Gouty, Laurie-Anne; Moos, Françoise C; Desarménien, Michel G

2006-07-01

Oxytocin (OT) and vasopressin (VP) autocontrol their secreting neurons in the supraoptic nucleus (SON) by modulating action potential firing through activation of specific metabotropic receptors. However, the mechanisms linking receptor activation to firing remain unknown. In almost all cell types, activation of plasma membrane metabotropic receptors triggers signalling cascades that induce mobilization of calcium from intracellular stores. In turn, emptying the calcium stores may evoke calcium influx through store-operated channels (SOCs), the functions of which remain largely unknown in neurons. In this study, we show that these channels play a key role in the SON, at least in the response to OT. In isolated rat SON neurons, store depletion by thapsigargin induced an influx of calcium, demonstrating the presence of SOCs in these neurons. This calcium influx was specifically inhibited by 0.2 mM 1-(2-trifluoromethylphenyl-)imidazole (TRIM). At 2 mM, this compound affected neither the resting electrophysiological properties nor the voltage-dependant inward currents. In fresh slices, TRIM (2 mM) did not affect the resting potential of SON neurons, action potential characteristics, spontaneous action potential firing or synaptic activity; this compound thus appears to be a specific blocker of SOCs in SON neurons. TRIM (0.2 mM) specifically reduced the increase in action potential firing triggered by OT but did not affect the VP-induced response. These observations demonstrate that store operated channels exist in hypothalamic neurons and specifically mediate the response to OT in the SON.

Beat-to-Beat Variation in Periodicity of Local Calcium Releases Contributes to Intrinsic Variations of Spontaneous Cycle Length in Isolated Single Sinoatrial Node Cells

PubMed Central

Monfredi, Oliver; Maltseva, Larissa A.; Spurgeon, Harold A.; Boyett, Mark R.; Lakatta, Edward G.; Maltsev, Victor A.

2013-01-01

Spontaneous, submembrane local Ca2+ releases (LCRs) generated by the sarcoplasmic reticulum in sinoatrial nodal cells, the cells of the primary cardiac pacemaker, activate inward Na+/Ca2+-exchange current to accelerate the diastolic depolarization rate, and therefore to impact on cycle length. Since LCRs are generated by Ca2+ release channel (i.e. ryanodine receptor) openings, they exhibit a degree of stochastic behavior, manifested as notable cycle-to-cycle variations in the time of their occurrence. Aim The present study tested whether variation in LCR periodicity contributes to intrinsic (beat-to-beat) cycle length variability in single sinoatrial nodal cells. Methods We imaged single rabbit sinoatrial nodal cells using a 2D-camera to capture LCRs over the entire cell, and, in selected cells, simultaneously measured action potentials by perforated patch clamp. Results LCRs begin to occur on the descending part of the action potential-induced whole-cell Ca2+ transient, at about the time of the maximum diastolic potential. Shortly after the maximum diastolic potential (mean 54±7.7 ms, n = 14), the ensemble of waxing LCR activity converts the decay of the global Ca2+ transient into a rise, resulting in a late, whole-cell diastolic Ca2+ elevation, accompanied by a notable acceleration in diastolic depolarization rate. On average, cells (n = 9) generate 13.2±3.7 LCRs per cycle (mean±SEM), varying in size (7.1±4.2 µm) and duration (44.2±27.1 ms), with both size and duration being greater for later-occurring LCRs. While the timing of each LCR occurrence also varies, the LCR period (i.e. the time from the preceding Ca2+ transient peak to an LCR’s subsequent occurrence) averaged for all LCRs in a given cycle closely predicts the time of occurrence of the next action potential, i.e. the cycle length. Conclusion Intrinsic cycle length variability in single sinoatrial nodal cells is linked to beat-to-beat variations in the average period of individual LCRs each cycle. PMID:23826247

Forced cell cycle exit and modulation of GABAA, CREB, and GSK3β signaling promote functional maturation of induced pluripotent stem cell-derived neurons.

PubMed

Telezhkin, Vsevolod; Schnell, Christian; Yarova, Polina; Yung, Sun; Cope, Emma; Hughes, Alis; Thompson, Belinda A; Sanders, Philip; Geater, Charlene; Hancock, Jane M; Joy, Shona; Badder, Luned; Connor-Robson, Natalie; Comella, Andrea; Straccia, Marco; Bombau, Georgina; Brown, Jon T; Canals, Josep M; Randall, Andrew D; Allen, Nicholas D; Kemp, Paul J

2016-04-01

Although numerous protocols have been developed for differentiation of neurons from a variety of pluripotent stem cells, most have concentrated on being able to specify effectively appropriate neuronal subtypes and few have been designed to enhance or accelerate functional maturity. Of those that have, most employ time courses of functional maturation that are rather protracted, and none have fully characterized all aspects of neuronal function, from spontaneous action potential generation through to postsynaptic receptor maturation. Here, we describe a simple protocol that employs the sequential addition of just two supplemented media that have been formulated to separate the two key phases of neural differentiation, the neurogenesis and synaptogenesis, each characterized by different signaling requirements. Employing these media, this new protocol synchronized neurogenesis and enhanced the rate of maturation of pluripotent stem cell-derived neural precursors. Neurons differentiated using this protocol exhibited large cell capacitance with relatively hyperpolarized resting membrane potentials; moreover, they exhibited augmented: 1) spontaneous electrical activity; 2) regenerative induced action potential train activity; 3) Na(+) current availability, and 4) synaptic currents. This was accomplished by rapid and uniform development of a mature, inhibitory GABAAreceptor phenotype that was demonstrated by Ca(2+) imaging and the ability of GABAAreceptor blockers to evoke seizurogenic network activity in multielectrode array recordings. Furthermore, since this protocol can exploit expanded and frozen prepatterned neural progenitors to deliver mature neurons within 21 days, it is both scalable and transferable to high-throughput platforms for the use in functional screens. Copyright © 2016 the American Physiological Society.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Catterall, Simon; Veernala, Aarti

We construct a lattice theory with one exact supersymmetry which consists of fields transforming in both the adjoint and fundamental representations of a U(Nc) gauge group. In addition to gluons and gluinos, the theory contains Nf flavors of fermion in the fundamental representation along with their scalar partners and is invariant under a global U(Nf) flavor symmetry. The lattice action contains an additional Fayet-Iliopoulos term which can be used to generate a scalar potential. We perform numerical simulations that corroborate the theoretical expectation that supersymmetry is spontaneously broken for Nf

Twitch and tetanic force responses and longitudinal propagation of action potentials in skinned skeletal muscle fibres of the rat

PubMed Central

Posterino, G S; Lamb, G D; Stephenson, D G

2000-01-01

Transverse electrical field stimulation (50 V cm−1, 2 ms duration) of mechanically skinned skeletal muscle fibres of the rat elicited twitch and tetanic force responses (36 ± 4 and 83 ± 4 % of maximum Ca2+-activated force, respectively; n = 23) closely resembling those in intact fibres. The responses were steeply dependent on the field strength and were eliminated by inclusion of 10 μm tetrodotoxin (TTX) in the (sealed) transverse tubular (T-) system of the skinned fibres and by chronic depolarisation of the T-system. Spontaneous twitch-like activity occurred sporadically in many fibres, producing near maximal force in some instances (mean time to peak: 190 ± 40 ms; n = 4). Such responses propagated as a wave of contraction longitudinally along the fibre at a velocity of 13 ± 3 mm s−1 (n = 7). These spontaneous contractions were also inhibited by inclusion of TTX in the T-system and by chronic depolarisation. We examined whether the T-tubular network was interconnected longitudinally using fibre segments that were skinned for only ∼2/3 of their length, leaving the remainder of each segment intact with its T-system open to the bathing solution. After such fibres were exposed to TTX (60 μm), the adjacent skinned region (with its T-system not open to the solution) became unresponsive to subsequent electrical stimulation in ∼50 % of cases (7/15), indicating that TTX was able to diffuse longitudinally inside the fibre via the tubular network over hundreds of sarcomeres. These experiments show that excitation–contraction coupling in mammalian muscle fibres involves action potential propagation both transversally and longitudinally within the tubular system. Longitudinal propagation of action potentials inside skeletal muscle fibres is likely to be an important safety mechanism for reducing conduction failure during fatigue and explains why, in developing skeletal muscle, the T-system first develops as an internal longitudinal network. PMID:10944176

The role of current affect, anticipated affect and spontaneous self-affirmation in decisions to receive self-threatening genetic risk information.

PubMed

Ferrer, Rebecca A; Taber, Jennifer M; Klein, William M P; Harris, Peter R; Lewis, Katie L; Biesecker, Leslie G

2015-01-01

One reason for not seeking personally threatening information may be negative current and anticipated affective responses. We examined whether current (e.g., worry) and anticipated negative affect predicted intentions to seek sequencing results in the context of an actual genomic sequencing trial (ClinSeq®; n = 545) and whether spontaneous self-affirmation mitigated any (negative) association between affect and intentions. Anticipated affective response negatively predicted intentions to obtain and share results pertaining to both medically actionable and non-actionable disease, whereas current affect was only a marginal predictor. The negative association between anticipated affect and intentions to obtain results pertaining to non-actionable disease was weaker in individuals who were higher in spontaneous self-affirmation. These results have implications for the understanding of current and anticipated affect, self-affirmation and consequential decision-making and contribute to a growing body of evidence on the role of affect in medical decisions.

The perception of musical spontaneity in improvised and imitated jazz performances.

PubMed

Engel, Annerose; Keller, Peter E

2011-01-01

The ability to evaluate spontaneity in human behavior is called upon in the esthetic appreciation of dramatic arts and music. The current study addresses the behavioral and brain mechanisms that mediate the perception of spontaneity in music performance. In a functional magnetic resonance imaging experiment, 22 jazz musicians listened to piano melodies and judged whether they were improvised or imitated. Judgment accuracy (mean 55%; range 44-65%), which was low but above chance, was positively correlated with musical experience and empathy. Analysis of listeners' hemodynamic responses revealed that amygdala activation was stronger for improvisations than imitations. This activation correlated with the variability of performance timing and intensity (loudness) in the melodies, suggesting that the amygdala is involved in the detection of behavioral uncertainty. An analysis based on the subjective classification of melodies according to listeners' judgments revealed that a network including the pre-supplementary motor area, frontal operculum, and anterior insula was most strongly activated for melodies judged to be improvised. This may reflect the increased engagement of an action simulation network when melodic predictions are rendered challenging due to perceived instability in the performer's actions. Taken together, our results suggest that, while certain brain regions in skilled individuals may be generally sensitive to objective cues to spontaneity in human behavior, the ability to evaluate spontaneity accurately depends upon whether an individual's action-related experience and perspective taking skills enable faithful internal simulation of the given behavior.

The Perception of Musical Spontaneity in Improvised and Imitated Jazz Performances

PubMed Central

Engel, Annerose; Keller, Peter E.

2011-01-01

The ability to evaluate spontaneity in human behavior is called upon in the esthetic appreciation of dramatic arts and music. The current study addresses the behavioral and brain mechanisms that mediate the perception of spontaneity in music performance. In a functional magnetic resonance imaging experiment, 22 jazz musicians listened to piano melodies and judged whether they were improvised or imitated. Judgment accuracy (mean 55%; range 44–65%), which was low but above chance, was positively correlated with musical experience and empathy. Analysis of listeners’ hemodynamic responses revealed that amygdala activation was stronger for improvisations than imitations. This activation correlated with the variability of performance timing and intensity (loudness) in the melodies, suggesting that the amygdala is involved in the detection of behavioral uncertainty. An analysis based on the subjective classification of melodies according to listeners’ judgments revealed that a network including the pre-supplementary motor area, frontal operculum, and anterior insula was most strongly activated for melodies judged to be improvised. This may reflect the increased engagement of an action simulation network when melodic predictions are rendered challenging due to perceived instability in the performer's actions. Taken together, our results suggest that, while certain brain regions in skilled individuals may be generally sensitive to objective cues to spontaneity in human behavior, the ability to evaluate spontaneity accurately depends upon whether an individual's action-related experience and perspective taking skills enable faithful internal simulation of the given behavior. PMID:21738518

The neural basis of the imitation drive

PubMed Central

Sugiura, Motoaki; Nozawa, Takayuki; Kotozaki, Yuka; Yomogida, Yukihito; Ihara, Mizuki; Akimoto, Yoritaka; Thyreau, Benjamin; Izumi, Shinichi; Kawashima, Ryuta

2016-01-01

Spontaneous imitation is assumed to underlie the acquisition of important skills by infants, including language and social interaction. In this study, functional magnetic resonance imaging (fMRI) was used to examine the neural basis of ‘spontaneously’ driven imitation, which has not yet been fully investigated. Healthy participants were presented with movie clips of meaningless bimanual actions and instructed to observe and imitate them during an fMRI scan. The participants were subsequently shown the movie clips again and asked to evaluate the strength of their ‘urge to imitate’ (Urge) for each action. We searched for cortical areas where the degree of activation positively correlated with Urge scores; significant positive correlations were observed in the right supplementary motor area (SMA) and bilateral midcingulate cortex (MCC) under the imitation condition. These areas were not explained by explicit reasons for imitation or the kinematic characteristics of the actions. Previous studies performed in monkeys and humans have implicated the SMA and MCC/caudal cingulate zone in voluntary actions. This study also confirmed the functional connectivity between Urge and imitation performance using a psychophysiological interaction analysis. Thus, our findings reveal the critical neural components that underlie spontaneous imitation and provide possible reasons why infants imitate spontaneously. PMID:26168793

Estradiol-modified prolactin secretion independently of action potentials and Ca2+ and blockade of outward potassium currents in GH3 cells.

PubMed

Sánchez, Manuel; Suárez, Lorena; Cantabrana, Begoña; Bordallo, Javier

2017-01-01

Estrogens facilitate prolactin (PRL) secretion acting on pituitary cells. In GH 3 cells, estradiol induces acute action potentials and oscillations of intracellular Ca 2+ associated with the secretagogue function. Estradiol modulates several ion channels which may affect the action potential rate and the release of PRL in lactotroph cells, which might depend on its concentration. The aims were to characterize the acute effect of supraphysiological concentrations of estradiol on Ca 2+ and noninactivating K + currents and measure the effect on the spontaneous action potentials and PRL release in the somatolactotroph cell line, GH 3 . Electrophysiological studies were carried out by voltage- and current-clamp techniques and ELISA determination of PRL secretion. Pharmacological concentrations of estradiol (above 1 μM), without a latency period, blocked Ca 2+ channels and noninactivating K + currents, including the large-conductance voltage- and Ca 2+ -activated K + channels (BK), studied in whole-cell nystatin perforated and in excided inside-out patches of GH 3 and CHO cells, transiently transfected with the human α-pore forming subunit of BK. The effect on BK was contrary to the agonist effect associated with the regulatory β 1 -subunits of the BK, which GH 3 cells lack, but its transient transfection did not modify the noninactivating current blockade, suggesting a different mechanism of regulation. Estradiol, at the same concentration range, acutely decreased the frequency of action potentials, an expected effect as consequence of the Ca 2+ channel blockade. Despite this, PRL secretion initially increased, followed by a decrease in long-term incubations. This suggests that, in GH 3 cells, supraphysiological concentrations of estradiol modulating PRL secretion are partially independent of extracellular Ca 2+ influx.

An Integrated Circuit for Simultaneous Extracellular Electrophysiology Recording and Optogenetic Neural Manipulation

PubMed Central

Chen, Chang Hao; McCullagh, Elizabeth A.; Pun, Sio Hang; Mak, Peng Un; Vai, Mang I; Mak, Pui In; Klug, Achim; Lei, Tim C.

2017-01-01

The ability to record and to control action potential firing in neuronal circuits of the brain is critical to understand how the brain functions on the cellular and network levels. Recent development of optogenetic proteins allows direct stimulation or inhibition of action potential firing of neurons upon optical illumination. In this paper, we combined a low-noise and high input impedance (or low input capacitance) neural recording amplifier, and a high current laser/LED driver in a monolithic integrated circuit (IC) for simultaneous neural recording and optogenetic neural control. The low input capacitance of the amplifier (9.7 pF) was achieved through adding a dedicated unity gain input stage optimized for high impedance metal electrodes. The input referred noise of the amplifier was measured to be 4.57 µVrms, which is lower than the estimated thermal noise of the metal electrode. Thus, action potentials originating from a single neuron can be recorded with a signal-to-noise ratio of ~6.6. The LED/laser current driver delivers a maximum current of 330 mA to generate adequate light for optogenetic control. We experimentally tested the functionality of the IC with an anesthetized Mongolian gerbil and recorded auditory stimulated action potentials from the inferior colliculus. Furthermore, we showed that spontaneous firing of 5th (trigeminal) nerve fibers was inhibited using the optogenetic protein Halorhodopsin. A noise model was also derived including the equivalent electronic components of the metal electrode and the high current driver to guide the design. PMID:28221990

The pacemaker activity generating the intrinsic myogenic contraction of the dorsal vessel of Tenebrio molitor (Coleoptera).

PubMed

Markou, T; Theophilidis, G

2000-11-01

Combined intracellular and extracellular recordings from various parts of the isolated dorsal vessel of Tenebrio molitor revealed some of the following electrophysiological properties of the heart and the aorta. (i) The wave of depolarization causing forward pulsation of the dorsal vessel was always transmitted from posterior to anterior, with a conduction velocity of 0.014 m s(-1) in the heart and 0.001 m s(-1) in the aorta when the heart rate was 60 beats min(-1). (ii) There was no pacemaker activity in the aorta. (iii) The duration of the compound action potential in the aortic muscle depended on the duration of the pacemaker action potential generated in the heart. (iv) Isolated parts of the heart continued to contract rhythmically for hours, indicating powerful pacemaker activity in individual cardiac segments. (v) There was a direct relationship between action potential duration and the length of the preceding diastolic interval. (vi) The rhythmic wave of depolarization was dependent on the influx of Ca(2+). (vii) The recovery of the electrical properties of myocardial cells that had been disrupted by sectioning was rapid. (viii) In hearts sectioned into two halves, the rhythmic pacemaker action potentials recorded simultaneously from the two isolated halves eventually drifted out of phase, but they had the same intrinsic frequency. In the light of these data, we discuss two alternative models for the generation of spontaneous rhythmic pumping movements of the heart and aorta.

The afterhyperpolarizing potential following a train of action potentials is suppressed in an acute epilepsy model in the rat Cornu Ammonis 1 area.

PubMed

Kernig, K; Kirschstein, T; Würdemann, T; Rohde, M; Köhling, R

2012-01-10

In hippocampal Cornu Ammonis 1 (CA1) neurons, a prolonged depolarization evokes a train of action potentials followed by a prominent afterhyperpolarizing potential (AHP), which critically dampens neuronal excitability. Because it is not known whether epileptiform activity alters the AHP and whether any alteration of the AHP is independent of inhibition, we acutely induced epileptiform activity by bath application of the GABA(A) receptor blocker gabazine (5 μM) in the rat hippocampal slice preparation and studied its impact on the AHP using intracellular recordings. Following 10 min of gabazine wash-in, slices started to develop spontaneous epileptiform discharges. This disinhibition was accompanied by a significant shift of the resting membrane potential of CA1 neurons to more depolarized values. Prolonged depolarizations (600 ms) elicited a train of action potentials, the number of which was not different between baseline and gabazine treatment. However, the AHP following the train of action potentials was significantly reduced after 20 min of gabazine treatment. When the induction of epileptiform activity was prevented by co-application of 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX, 10 μM) and D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5, 50 μM) to block α-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) and N-methyl-d-aspartate (NMDA) receptors, respectively, the AHP was preserved despite of GABA(A) receptor inhibition suggesting that the epileptiform activity was required to suppress the AHP. Moreover, the AHP was also preserved when the slices were treated with the protein kinase blockers H-9 (100 μM) and H-89 (1 μM). These results demonstrate that the AHP following a train of action potentials is rapidly suppressed by acutely induced epileptiform activity due to a phosphorylation process-presumably involving protein kinase A. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Emergence of order in visual system development.

PubMed Central

Shatz, C J

1996-01-01

Neural connections in the adult central nervous system are highly precise. In the visual system, retinal ganglion cells send their axons to target neurons in the lateral geniculate nucleus (LGN) in such a way that axons originating from the two eyes terminate in adjacent but nonoverlapping eye-specific layers. During development, however, inputs from the two eyes are intermixed, and the adult pattern emerges gradually as axons from the two eyes sort out to form the layers. Experiments indicate that the sorting-out process, even though it occurs in utero in higher mammals and always before vision, requires retinal ganglion cell signaling; blocking retinal ganglion cell action potentials with tetrodotoxin prevents the formation of the layers. These action potentials are endogenously generated by the ganglion cells, which fire spontaneously and synchronously with each other, generating "waves" of activity that travel across the retina. Calcium imaging of the retina shows that the ganglion cells undergo correlated calcium bursting to generate the waves and that amacrine cells also participate in the correlated activity patterns. Physiological recordings from LGN neurons in vitro indicate that the quasiperiodic activity generated by the retinal ganglion cells is transmitted across the synapse between ganglion cells to drive target LGN neurons. These observations suggest that (i) a neural circuit within the immature retina is responsible for generating specific spatiotemporal patterns of neural activity; (ii) spontaneous activity generated in the retina is propagated across central synapses; and (iii) even before the photoreceptors are present, nerve cell function is essential for correct wiring of the visual system during early development. Since spontaneously generated activity is known to be present elsewhere in the developing CNS, this process of activity-dependent wiring could be used throughout the nervous system to help refine early sets of neural connections into their highly precise adult patterns. Images Fig. 1 Fig. 4 PMID:8570602

Introduction of a method for quantitative evaluation of spontaneous motor activity development with age in infants.

PubMed

Disselhorst-Klug, Catherine; Heinze, Franziska; Breitbach-Faller, Nico; Schmitz-Rode, Thomas; Rau, Günter

2012-04-01

Coordination between perception and action is required to interact with the environment successfully. This is already trained by very young infants who perform spontaneous movements to learn how their body interacts with the environment. The strategies used by the infants for this purpose change with age. Therefore, very early progresses in action control made by the infants can be investigated by monitoring the development of spontaneous motor activity. In this paper, an objective method is introduced, which allows the quantitative evaluation of the development of spontaneous motor activity in newborns. The introduced methodology is based on the acquisition of spontaneous movement trajectories of the feet by 3D movement analysis and subsequent calculation of specific movement parameters from them. With these movement-based parameters, it was possible to provide an objective description of age-dependent developmental steps in healthy newborns younger than 6 months. Furthermore, it has been shown that pathologies like infantile cerebral palsy influence development of motor activity significantly. Since the introduced methodology is objective and quantitative, it is suitable to monitor how newborns train their cognitive processes, which will enable them to cope with their environment by motor interaction.

An integrate-and-fire model for synchronized bursting in a network of cultured cortical neurons.

PubMed

French, D A; Gruenstein, E I

2006-12-01

It has been suggested that spontaneous synchronous neuronal activity is an essential step in the formation of functional networks in the central nervous system. The key features of this type of activity consist of bursts of action potentials with associated spikes of elevated cytoplasmic calcium. These features are also observed in networks of rat cortical neurons that have been formed in culture. Experimental studies of these cultured networks have led to several hypotheses for the mechanisms underlying the observed synchronized oscillations. In this paper, bursting integrate-and-fire type mathematical models for regular spiking (RS) and intrinsic bursting (IB) neurons are introduced and incorporated through a small-world connection scheme into a two-dimensional excitatory network similar to those in the cultured network. This computer model exhibits spontaneous synchronous activity through mechanisms similar to those hypothesized for the cultured experimental networks. Traces of the membrane potential and cytoplasmic calcium from the model closely match those obtained from experiments. We also consider the impact on network behavior of the IB neurons, the geometry and the small world connection scheme.

The Use of Ratiometric Fluorescence Measurements of the Voltage Sensitive Dye Di-4-ANEPPS to Examine Action Potential Characteristics and Drug Effects on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

PubMed

Hortigon-Vinagre, M P; Zamora, V; Burton, F L; Green, J; Gintant, G A; Smith, G L

2016-12-01

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and higher throughput platforms have emerged as potential tools to advance cardiac drug safety screening. This study evaluated the use of high bandwidth photometry applied to voltage-sensitive fluorescent dyes (VSDs) to assess drug-induced changes in action potential characteristics of spontaneously active hiPSC-CM. Human iPSC-CM from 2 commercial sources (Cor.4U and iCell Cardiomyocytes) were stained with the VSD di-4-ANEPPS and placed in a specialized photometry system that simultaneously monitors 2 wavebands of emitted fluorescence, allowing ratiometric measurement of membrane voltage. Signals were acquired at 10 kHz and analyzed using custom software. Action potential duration (APD) values were normally distributed in cardiomyocytes (CMC) from both sources though the mean and variance differed significantly (APD 90 : 229 ± 15 ms vs 427 ± 49 ms [mean ± SD, P < 0.01]; average spontaneous cycle length: 0.99 ± 0.02 s vs 1.47 ± 0.35 s [mean ± SD, P < 0.01], Cor.4U vs iCell CMC, respectively). The 10-90% rise time of the AP (T rise ) was ∼6 ms and was normally distributed when expressed as 1/[Formula: see text] in both cell preparations. Both cell types showed a rate dependence analogous to that of adult human cardiac cells. Furthermore, nifedipine, ranolazine, and E4031 had similar effects on cardiomyocyte electrophysiology in both cell types. However, ranolazine and E4031 induced early after depolarization-like events and high intrinsic firing rates at lower concentrations in iCell CMC. These data show that VSDs provide a minimally invasive, quantitative, and accurate method to assess hiPSC-CM electrophysiology and detect subtle drug-induced effects for drug safety screening while highlighting a need to standardize experimental protocols across preparations. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

Microneurography in rats: a minimally invasive method to record single C-fiber action potentials from peripheral nerves in vivo.

PubMed

Serra, Jordi; Bostock, Hugh; Navarro, Xavier

2010-02-19

Microneurography is a method suitable for recording intraneural single or multiunit action potentials in conscious subjects. Microneurography has rarely been applied to animal experiments, where more invasive methods, like the teased fiber recording technique, are widely used. We have tested the feasibility of microneurographic recordings from the peripheral nerves of rats. Tungsten microelectrodes were inserted into the sciatic nerve at mid-thigh level. Single or multiunit action potentials evoked by regular electrical stimulation were recorded, digitized and displayed as a raster plot of latencies. The method allows unambiguous recording and recognition of single C-fiber action potentials from an in vivo preparation, with minimal disruption of the nerve being recorded. Multiple C-fibers can be recorded simultaneously for several hours, and if the animal is allowed to recover, repeated recording sessions can be obtained from the same nerve at the same level over a period of weeks or months. Also, single C units can be functionally identified by their changes in latency to natural stimuli, and insensitive units can be recognized as 'silent' nociceptors or sympathetic efferents by their distinctive profiles of activity-dependent slowing during repetitive electrical stimulation, or by the effect on spontaneous efferent activity of a proximal anesthetic block. Moreover, information about the biophysical properties of C axons can be obtained from their latency recovery cycles. Finally, we show that this preparation is potentially suitable for the study of C-fiber behavior in models of neuropathies and nerve lesions, both under resting conditions and in response to drug administration.

The sea anemone toxin AdE-1 modifies both sodium and potassium currents of rat cardiomyocytes.

PubMed

Nesher, Nir; Zlotkin, Eliahu; Hochner, Binyamin

2014-07-01

AdE-1, a cardiotonic peptide recently isolated from the sea anemone Aiptasia diaphana, contains 44 amino acids and has a molecular mass of 4907 Da. It was previously found to resemble other sea anemone type 1 and 2 Na+ channel toxins, enhancing contractions of rat cardiomyocytes and slowing their twitch relaxation; however, it did not induce spontaneous twitches. AdE-1 increased the duration of the cardiomyocyte action potential and decreased its amplitude and its time-to-peak in a concentration-dependent manner, without affecting its threshold and cell resting potential. Nor did it generate the early and delayed after-depolarizations characteristic of sea anemone Na+ channel toxins. To further understand its mechanism of action we investigated the effect of AdE-1 on the major ion currents of rat cardiomyocytes. In the present study we show that AdE-1 markedly slowed inactivation of the Na+ current, enhancing and prolonging the current influx with no effect on current activation, possibly through direct interaction with the site 3 receptor of the Na+ channel. No significant effect of AdE-1 on the Ca2+ current was observed, but, unexpectedly, AdE-1 significantly increased the amplitude of the transient component of the K+ current, shifting the current threshold to more negative membrane potentials. This effect on the K+ current has not been found in any other sea anemone toxin and may explain the exclusive reduction in action potential amplitude and the absence of the action potential disorders found with other toxins, such as early and delayed after-depolarizations.

"Unwilling" versus "Unable": Chimpanzees' Understanding of Human Intentional Action

ERIC Educational Resources Information Center

Call, Josep; Hare, Brian; Carpenter, Malinda; Tomasello, Michael

2004-01-01

Understanding the intentional actions of others is a fundamental part of human social cognition and behavior. An important question is therefore whether other animal species, especially our nearest relatives the chimpanzees, also understand the intentional actions of others. Here we show that chimpanzees spontaneously (without training) behave…

Tapping Into Rate Flexibility: Musical Training Facilitates Synchronization Around Spontaneous Production Rates

PubMed Central

Scheurich, Rebecca; Zamm, Anna; Palmer, Caroline

2018-01-01

The ability to flexibly adapt one’s behavior is critical for social tasks such as speech and music performance, in which individuals must coordinate the timing of their actions with others. Natural movement frequencies, also called spontaneous rates, constrain synchronization accuracy between partners during duet music performance, whereas musical training enhances synchronization accuracy. We investigated the combined influences of these factors on the flexibility with which individuals can synchronize their actions with sequences at different rates. First, we developed a novel musical task capable of measuring spontaneous rates in both musicians and non-musicians in which participants tapped the rhythm of a familiar melody while hearing the corresponding melody tones. The novel task was validated by similar measures of spontaneous rates generated by piano performance and by the tapping task from the same pianists. We then implemented the novel task with musicians and non-musicians as they synchronized tapping of a familiar melody with a metronome at their spontaneous rates, and at rates proportionally slower and faster than their spontaneous rates. Musicians synchronized more flexibly across rates than non-musicians, indicated by greater synchronization accuracy. Additionally, musicians showed greater engagement of error correction mechanisms than non-musicians. Finally, differences in flexibility were characterized by more recurrent (repetitive) and patterned synchronization in non-musicians, indicative of greater temporal rigidity. PMID:29681872

EEG Negativity in Fixations Used for Gaze-Based Control: Toward Converting Intentions into Actions with an Eye-Brain-Computer Interface

PubMed Central

Shishkin, Sergei L.; Nuzhdin, Yuri O.; Svirin, Evgeny P.; Trofimov, Alexander G.; Fedorova, Anastasia A.; Kozyrskiy, Bogdan L.; Velichkovsky, Boris M.

2016-01-01

We usually look at an object when we are going to manipulate it. Thus, eye tracking can be used to communicate intended actions. An effective human-machine interface, however, should be able to differentiate intentional and spontaneous eye movements. We report an electroencephalogram (EEG) marker that differentiates gaze fixations used for control from spontaneous fixations involved in visual exploration. Eight healthy participants played a game with their eye movements only. Their gaze-synchronized EEG data (fixation-related potentials, FRPs) were collected during game's control-on and control-off conditions. A slow negative wave with a maximum in the parietooccipital region was present in each participant's averaged FRPs in the control-on conditions and was absent or had much lower amplitude in the control-off condition. This wave was similar but not identical to stimulus-preceding negativity, a slow negative wave that can be observed during feedback expectation. Classification of intentional vs. spontaneous fixations was based on amplitude features from 13 EEG channels using 300 ms length segments free from electrooculogram contamination (200–500 ms relative to the fixation onset). For the first fixations in the fixation triplets required to make moves in the game, classified against control-off data, a committee of greedy classifiers provided 0.90 ± 0.07 specificity and 0.38 ± 0.14 sensitivity. Similar (slightly lower) results were obtained for the shrinkage Linear Discriminate Analysis (LDA) classifier. The second and third fixations in the triplets were classified at lower rate. We expect that, with improved feature sets and classifiers, a hybrid dwell-based Eye-Brain-Computer Interface (EBCI) can be built using the FRP difference between the intended and spontaneous fixations. If this direction of BCI development will be successful, such a multimodal interface may improve the fluency of interaction and can possibly become the basis for a new input device for paralyzed and healthy users, the EBCI “Wish Mouse.” PMID:27917105

Spontaneous Isomerization of Peptide Cation Radicals Following Electron Transfer Dissociation Revealed by UV-Vis Photodissociation Action Spectroscopy.

PubMed

Imaoka, Naruaki; Houferak, Camille; Murphy, Megan P; Nguyen, Huong T H; Dang, Andy; Tureček, František

2018-01-16

Peptide cation radicals of the z-type were produced by electron transfer dissociation (ETD) of peptide dications and studied by UV-Vis photodissociation (UVPD) action spectroscopy. Cation radicals containing the Asp (D), Asn (N), Glu (E), and Gln (Q) residues were found to spontaneously isomerize by hydrogen atom migrations upon ETD. Canonical N-terminal [z 4 + H] +● fragment ion-radicals of the R-C ● H-CONH- type, initially formed by N-C α bond cleavage, were found to be minor components of the stable ion fraction. Vibronically broadened UV-Vis absorption spectra were calculated by time-dependent density functional theory for several [ ● DAAR + H] + isomers and used to assign structures to the action spectra. The potential energy surface of [ ● DAAR + H] + isomers was mapped by ab initio and density functional theory calculations that revealed multiple isomerization pathways by hydrogen atom migrations. The transition-state energies for the isomerizations were found to be lower than the dissociation thresholds, accounting for the isomerization in non-dissociating ions. The facile isomerization in [ ● XAAR + H] + ions (X = D, N, E, and Q) was attributed to low-energy intermediates having the radical defect in the side chain that can promote hydrogen migration along backbone C α positions. A similar side-chain mediated mechanism is suggested for the facile intermolecular hydrogen migration between the c- and [z + H] ● -ETD fragments containing Asp, Asn, Glu, and Gln residues. Graphical Abstract ᅟ.

Spontaneous Isomerization of Peptide Cation Radicals Following Electron Transfer Dissociation Revealed by UV-Vis Photodissociation Action Spectroscopy

NASA Astrophysics Data System (ADS)

Imaoka, Naruaki; Houferak, Camille; Murphy, Megan P.; Nguyen, Huong T. H.; Dang, Andy; Tureček, František

2018-01-01

Peptide cation radicals of the z-type were produced by electron transfer dissociation (ETD) of peptide dications and studied by UV-Vis photodissociation (UVPD) action spectroscopy. Cation radicals containing the Asp (D), Asn (N), Glu (E), and Gln (Q) residues were found to spontaneously isomerize by hydrogen atom migrations upon ETD. Canonical N-terminal [z4 + H]+● fragment ion-radicals of the R-C●H-CONH- type, initially formed by N-Cα bond cleavage, were found to be minor components of the stable ion fraction. Vibronically broadened UV-Vis absorption spectra were calculated by time-dependent density functional theory for several [●DAAR + H]+ isomers and used to assign structures to the action spectra. The potential energy surface of [●DAAR + H]+ isomers was mapped by ab initio and density functional theory calculations that revealed multiple isomerization pathways by hydrogen atom migrations. The transition-state energies for the isomerizations were found to be lower than the dissociation thresholds, accounting for the isomerization in non-dissociating ions. The facile isomerization in [●XAAR + H]+ ions (X = D, N, E, and Q) was attributed to low-energy intermediates having the radical defect in the side chain that can promote hydrogen migration along backbone Cα positions. A similar side-chain mediated mechanism is suggested for the facile intermolecular hydrogen migration between the c- and [z + H]●-ETD fragments containing Asp, Asn, Glu, and Gln residues. [Figure not available: see fulltext.

Clarithromycin increases neuronal excitability in CA3 pyramidal neurons through a reduction in GABAergic signaling

PubMed Central

Elder, Courtney C.; García, Paul S.

2016-01-01

Antibiotics are used in the treatment and prevention of bacterial infections, but effects on neuron excitability have been documented. A recent study demonstrated that clarithromycin alleviates daytime sleepiness in hypersomnia patients (Trotti LM, Saini P, Freeman AA, Bliwise DL, García PS, Jenkins A, Rye DB. J Psychopharmacol 28: 697–702, 2014). To explore the potential application of clarithromycin as a stimulant, we performed whole cell patch-clamp recordings in rat pyramidal cells from the CA3 region of hippocampus. In the presence of the antibiotic, rheobase current was reduced by 50%, F-I relationship (number of action potentials as a function of injected current) was shifted to the left, and the resting membrane potential was more depolarized. Clarithromycin-induced hyperexcitability was dose dependent; doses of 30 and 300 μM clarithromycin significantly increased the firing frequency and membrane potential compared with controls (P = 0.003, P < 0.0001). We hypothesized that clarithromycin enhanced excitability by reducing GABAA receptor activation. Clarithromycin at 30 μM significantly reduced (P = 0.001) the amplitude of spontaneous miniature inhibitory GABAergic currents and at 300 μM had a minor effect on action potential width. Additionally, we tested the effect of clarithromycin in an ex vivo seizure model by evaluating its effect on spontaneous local field potentials. Bath application of 300 μM clarithromycin enhanced burst frequency twofold compared with controls (P = 0.0006). Taken together, these results suggest that blocking GABAergic signaling with clarithromycin increases cellular excitability and potentially serves as a stimulant, facilitating emergence from anesthesia or normalizing vigilance in hypersomnia and narcolepsy. However, the administration of clarithromycin should be carefully considered in patients with seizure disorders. NEW & NOTEWORTHY Clinical administration of the macrolide antibiotic clarithromycin has been associated with side effects such as mania, agitation, and delirium. Here, we investigated the adverse effects of this antibiotic on CA3 pyramidal cell excitability. Clarithromycin induces hyperexcitability in single neurons and is related to a reduction in GABAergic signaling. Our results support a potentially new application of clarithromycin as a stimulant to facilitate emergence from anesthesia or to normalize vigilance. PMID:27733592

The linear synchronization measures of uterine EMG signals: Evidence of synchronized action potentials during propagation.

PubMed

Domino, Malgorzata; Pawlinski, Bartosz; Gajewski, Zdzislaw

2016-11-01

Evaluation of synchronization between myoelectric signals can give new insights into the functioning of the complex system of porcine myometrium. We propose a model of uterine contractions according to the hypothesis of action potentials similarity which is possible to detect during propagation in the uterine wall. We introduce similarity measures based on the concept of synchronization as used in matching linear signals such as electromyographic (EMG) time series data. The aim was to present linear measures to assess synchronization between contractions in different topographic regions of the uterus. We use the cross-correlation function (ƒx,y[l], ƒy,z[l]) and the cross-coherence function (Cxy[ƒ], Cyz[ƒ]) to assess synchronization between three data series of a diestral uterine EMG bundles in porcine reproductive tract. Spontaneous uterine activity was recorded using telemetry method directly by three-channel transmitter and three silver bipolar needle electrodes sutured on different topographic regions of the reproductive tract in the sow. The results show the usefulness of the cross-coherence function in that synchronization between uterine horn and corpus uteri for multiple action potentials (bundles) could be observed. The EMG bundles synchronization may be used to investigate the direction and velocity of EMG signals propagation in porcine reproductive tract. Copyright © 2016 Elsevier Inc. All rights reserved.

[Effects of transections and electrical coagulations in the medulla oblongata upon the activities in the respiratory muscles of the crucian carp (author's transl)].

PubMed

Fukuda, H

1975-06-01

The following conclusions may be drawn from the results in this work. The respiratory cycles are formed by the neuronal machinery in the reticular formation under the posterior part of the vagal motor nucleus. The motor neurones or the neuronal networks composing the motor nucleus of the respiratory muscles tonically discharge the action potentials, when the neurones or the networks are released from the inhibitory influences of the interneurones connecting the neuronal machinery to the motor neurones. Furthermore, the interneurones probably generate the tonic discharges after removing the inhibitory influences of the other interneurones or the neuronal machinery on them. A reflex mouth closing is elicited by a mechanical stimulus applying on the upper lip. The motor neurones of the m. adductor mandibulae are activated via only one synapse in the reflex. The reflex action potentials recorded from the motor nerve reduce in amplitude at the resting phase of the nerve in the respiratory cycles. These results suggest that the respiratory motor neurones are by nature spontaneous generators of the tonic action potentials and, in the time of the normal breathing, the tonic activity is interrupted by an inhibitory influence of the neuronal machinery generating the respiratory cycles.

Blink and you’ll miss it: the role of blinking in the perception of magic tricks

PubMed Central

Nakano, Tamami

2016-01-01

Magicians use several techniques to deceive their audiences, including, for example, the misdirection of attention and verbal suggestion. We explored another potential stratagem, namely the relaxation of attention. Participants watched a video of a highly skilled magician whilst having their eye-blinks recorded. The timing of spontaneous eye-blinks was highly synchronized across participants. In addition, the synchronized blinks frequency occurred immediately after a seemingly impossible feat, and often coincided with actions that the magician wanted to conceal from the audience. Given that blinking is associated with the relaxation of attention, these findings suggest that blinking plays an important role in the perception of magic, and that magicians may utilize blinking and the relaxation of attention to hide certain secret actions. PMID:27069808

Blink and you'll miss it: the role of blinking in the perception of magic tricks.

PubMed

Wiseman, Richard J; Nakano, Tamami

2016-01-01

Magicians use several techniques to deceive their audiences, including, for example, the misdirection of attention and verbal suggestion. We explored another potential stratagem, namely the relaxation of attention. Participants watched a video of a highly skilled magician whilst having their eye-blinks recorded. The timing of spontaneous eye-blinks was highly synchronized across participants. In addition, the synchronized blinks frequency occurred immediately after a seemingly impossible feat, and often coincided with actions that the magician wanted to conceal from the audience. Given that blinking is associated with the relaxation of attention, these findings suggest that blinking plays an important role in the perception of magic, and that magicians may utilize blinking and the relaxation of attention to hide certain secret actions.

Stimfit: quantifying electrophysiological data with Python

PubMed Central

Guzman, Segundo J.; Schlögl, Alois; Schmidt-Hieber, Christoph

2013-01-01

Intracellular electrophysiological recordings provide crucial insights into elementary neuronal signals such as action potentials and synaptic currents. Analyzing and interpreting these signals is essential for a quantitative understanding of neuronal information processing, and requires both fast data visualization and ready access to complex analysis routines. To achieve this goal, we have developed Stimfit, a free software package for cellular neurophysiology with a Python scripting interface and a built-in Python shell. The program supports most standard file formats for cellular neurophysiology and other biomedical signals through the Biosig library. To quantify and interpret the activity of single neurons and communication between neurons, the program includes algorithms to characterize the kinetics of presynaptic action potentials and postsynaptic currents, estimate latencies between pre- and postsynaptic events, and detect spontaneously occurring events. We validate and benchmark these algorithms, give estimation errors, and provide sample use cases, showing that Stimfit represents an efficient, accessible and extensible way to accurately analyze and interpret neuronal signals. PMID:24600389

[Effect of gamma-aminobutyric acid on peripheral mechanisms regulating autonomic functions].

PubMed

Godovalova, L A

1976-01-01

Experiments with cats ascertained the potentiating action of GABA (100,300,500 mg/kg) on the pressor reactions of the small intestine vessels, the systemic arterial pressure, depressing (100 mg/kg) and facilitating (500 mg/kg) effect upon the reactions of inhibition of the small intestine motor activity evoked by the efferent stimulation of the celiac nerve. Adrenolytics (dihydroergotoxin, inderal) abolished the facilitating effects of GABA. The latter (0.01 solution) inhibited spontaneous contractions of isolated small intestine lengths. As proved histochemically GABA (500 mg/kg) reduces the catecholamines content in the suprarenals, in the solar plexus ganglia and in vessles "in vivo". It also increases the catecholamines content in the small intestine wall in experiments in vivo and reduces in vitro tests. The potentiating action of GABA on the vegetative reactions in efferent stimulation of the ciliac nerve occurs, apparently, due to an increased ejection of catecholamines by suprarenals and lowered the content of catecholamines in the solar plexus ganglia, which causes facilitated conduction of excitation in the ganglia.

Action potential broadening in a presynaptic channelopathy

NASA Astrophysics Data System (ADS)

Begum, Rahima; Bakiri, Yamina; Volynski, Kirill E.; Kullmann, Dimitri M.

2016-07-01

Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca2+ influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction.

Agonist-induced modulation of inverse agonist efficacy at the beta 2-adrenergic receptor.

PubMed

Chidiac, P; Nouet, S; Bouvier, M

1996-09-01

Sustained stimulation of several G protein-coupled receptors is known to lead to a reduction in the signaling efficacy. This phenomenon, named agonist-induced desensitization, has been best studied for the beta 2-adrenergic receptor (AR) and is characterized by a decreased efficacy of beta-adrenergic agonists to stimulate the adenylyl cyclase activity. Recently, several beta-adrenergic ligands were found to inhibit the spontaneous agonist-independent activity of the beta 2AR. These compounds, termed inverse agonists, have different inhibitory efficacies, ranging from almost neutral antagonists to full inverse agonists. The current study was undertaken to determine whether, as is the case for agonists, desensitization can affect the efficacies of inverse agonists. Agonist-promoted desensitization of the human beta 2AR expressed in Sf9 cells potentiated the inhibitory actions of the inverse agonists, with the extent of the potentiation being inversely proportional to their intrinsic activity. For example, desensitization increased the inhibitory action of the weak inverse agonist labetalol by 29%, whereas inhibition of the spontaneous activity by the strong inverse agonist timolol was not enhanced by the desensitizing stimuli. Interestingly, dichloroisoproterenol acted stochastically as either a weak partial agonist or a weak inverse agonist in control conditions but always behaved as an inverse agonist after desensitization. These data demonstrate that like for agonists, the efficacies of inverse agonists can be modulated by a desensitizing treatment. Also, the data show that the initial state of the receptor can determine whether a ligand behaves as a partial agonist or an inverse agonist.

Spontaneous Gestures during Mental Rotation Tasks: Insights into the Microdevelopment of the Motor Strategy

ERIC Educational Resources Information Center

Chu, Mingyuan; Kita, Sotaro

2008-01-01

This study investigated the motor strategy involved in mental rotation tasks by examining 2 types of spontaneous gestures (hand-object interaction gestures, representing the agentive hand action on an object, vs. object-movement gestures, representing the movement of an object by itself) and different types of verbal descriptions of rotation.…

The Development of Spontaneous Gender Stereotyping in Childhood: Relations to Stereotype Knowledge and Stereotype Flexibility

ERIC Educational Resources Information Center

Banse, Rainer; Gawronski, Bertram; Rebetez, Christine; Gutt, Helene; Morton, J. Bruce

2010-01-01

The development of spontaneous gender stereotyping in children was investigated using the newly developed Action Interference Paradigm (AIP). This task consists of assigning gender-stereotypical toys as quickly as possible to boys and girls in either a stereotype-congruent or a stereotype-incongruent manner. A pilot study with 38 children (mean…

Spontaneous generation in medieval Jewish philosophy and theology.

PubMed

Gaziel, Ahuva

2012-01-01

The concept of life forms emerging from inanimate matter--spontaneous generation--was widely accepted until the nineteenth century. Several medieval Jewish scholars acknowledged this scientific theory in their philosophical and religious contemplations. Quite interestingly, it served to reinforce diverse, or even opposite, theological conclusions. One approach excluded spontaneously-generated living beings form the biblical account of creation or the story of the Deluge. Underlying this view is an understanding that organisms that generate spontaneously evolve continuously in nature and, therefore, do not require divine intervention in their formation or survival during disastrous events. This naturalistic position reduces the miraculous dimension of reality. Others were of the opinion that spontaneous generation is one of the extraordinary marvels exhibited in this world and, accordingly, this interpretation served to accentuate the divine aspect of nature. References to spontaneous generation also appear in legal writings, influencing practical applications such as dietary laws and actions forbidden on the Sabbath.

The development of spontaneous gender stereotyping in childhood: relations to stereotype knowledge and stereotype flexibility.

PubMed

Banse, Rainer; Gawronski, Bertram; Rebetez, Christine; Gutt, Hélène; Morton, J Bruce

2010-03-01

The development of spontaneous gender stereotyping in children was investigated using the newly developed Action Interference Paradigm (AIP). This task consists of assigning gender-stereotypical toys as quickly as possible to boys and girls in either a stereotype-congruent or a stereotype-incongruent manner. A pilot study with 38 children (mean age 5.1 years) provided evidence for spontaneous gender stereotyping in the AIP, which was reflected in higher latencies for stereotype-incongruent compared with stereotype-congruent toy assignments. The main study, with 66 children (aged 5, 8 and 11 years), compared the development of spontaneous stereotyping with established measures of stereotype flexibility and stereotype knowledge. Stereotype flexibility showed a strong increase from age 5 to 11. In contrast, stereotype knowledge and spontaneous stereotyping remained stable at high levels. The results provide evidence for a dissociation between stereotype flexibility and spontaneous stereotyping, suggesting that spontaneous stereotyping may be more closely related to stereotype knowledge than to stereotype flexibility.

[Intranasal epitalon infusion modulates neuronal activity in the rat neocortex].

PubMed

Sibarov, D A; Vol'nova, A B; Frolov, D S; Nosdrachev, A D

2006-08-01

Properties of tetrapeptide epitalon (Ala-Glu-Asp-Gly) constructed on the basis of pineal peptide extract, have been studied. The intranasal infusions: a noninvasive way to deliver this peptide to CNS hypassing the blood-brain barrier, was used. The aim of the study is to estimate epitalon action on rat motor cortex spontaneous activity. Wistar male rats were anesthetized with urethane (1 g/kg). Extracellular unit recording was made using glass microelectrodes (1-2 MOhm). After recording of spontaneous activity (10-15 min), epitalon intranasal infusion (2 ng) was followed by 30-minute recording. Within a few minutes after the infusion, significant activation of neural activity was observed (2-2.5-fold higher frequency of neuronal spikes). Complex response consisting of several phases was identified in some recordings. The spikes frequency growth during 5 to 7 min (first phase) after the infusion was followed by the second (11-12 min) and the third (17-18 min) phases. An increase of neuronal spontaneous activity was conditioned by the higher frequency of already active units and by the involvement of previously silent cells. At least the first phase of epitalon action can be explained by direct action of the peptide on the cells of the motor cortex.

Electrical properties of the costo-uterine muscle of the guinea-pig.

PubMed Central

Parkington, H C

1983-01-01

The spontaneous electrical and mechanical activity of the costo-uterine muscle of the guinea-pig are described. The spontaneous electrical activity, recorded intracellularly, is similar to that observed previously in longitudinal myometrium of rat (Marshall, 1959) and ionic substitution suggests that, though calcium may be the predominant ion carrying the current during the upstroke of the action potential, some influence of sodium cannot be ruled out. During dioestrus, when circulating progesterone levels are high, there is an increase in the resting membrane potential and a decrease in the frequency of electrical and mechanical activity. There is a two-fold decrease in the space constant (lambda) during dioestrus. At this time the membrane time constant (tau m) is also decreased. The diameter and length of the smooth muscle cells are smaller during dioestrus. However, the differences in cell diameter do not explain all of the differences observed in lambda at this time and it is suggested that there may be an increase in the resistance to current flow between cells. It is concluded that high circulating progesterone may bring about quiescence of target smooth muscle in two ways: by stabilizing the cell membrane and by restricting the spread of activity. PMID:6683758

Absence of spontaneous action anticipation by false belief attribution in children with autism spectrum disorder.

PubMed

Senju, Atsushi; Southgate, Victoria; Miura, Yui; Matsui, Tomoko; Hasegawa, Toshikazu; Tojo, Yoshikuni; Osanai, Hiroo; Csibra, Gergely

2010-05-01

Recently, a series of studies demonstrated false belief understanding in young children through completely nonverbal measures. These studies have revealed that children younger than 3 years of age, who consistently fail the standard verbal false belief test, can anticipate others' actions based on their attributed false beliefs. The current study examined whether children with autism spectrum disorder (ASD), who are known to have difficulties in the verbal false belief test, may also show such action anticipation in a nonverbal false belief test. We presented video stimuli of an actor watching an object being hidden in a box. The object was then displaced while the actor was looking away. We recorded children's eye movements and coded whether they spontaneously anticipated the actor's subsequent behavior, which could only have been predicted if they had attributed a false belief to her. Although typically developing children correctly anticipated the action, children with ASD failed to show such action anticipation. The results suggest that children with ASD have an impairment in false belief attribution, which is independent of their verbal ability.

Linear transformation of the encoding mechanism for light intensity underlies the paradoxical enhancement of cortical visual responses by sevoflurane.

PubMed

Arena, Alessandro; Lamanna, Jacopo; Gemma, Marco; Ripamonti, Maddalena; Ravasio, Giuliano; Zimarino, Vincenzo; De Vitis, Assunta; Beretta, Luigi; Malgaroli, Antonio

2017-01-01

The mechanisms of action of anaesthetics on the living brain are still poorly understood. In this respect, the analysis of the differential effects of anaesthetics on spontaneous and sensory-evoked cortical activity might provide important and novel cues. Here we show that the anaesthetic sevoflurane strongly silences the brain but potentiates in a dose- and frequency-dependent manner the cortical visual response. Such enhancement arises from a linear scaling by sevoflurane of the power-law relation between light intensity and the cortical response. The fingerprint of sevoflurane action suggests that circuit silencing can boost linearly synaptic responsiveness presumably by scaling the number of responding units and/or their correlation following a sensory stimulation. General anaesthetics, which are expected to silence brain activity, often spare sensory responses. To evaluate differential effects of anaesthetics on spontaneous and sensory-evoked cortical activity, we characterized their modulation by sevoflurane and propofol. Power spectra and the bust-suppression ratio from EEG data were used to evaluate anaesthesia depth. ON and OFF cortical responses were elicited by light pulses of variable intensity, duration and frequency, during light and deep states of anaesthesia. Both anaesthetics reduced spontaneous cortical activity but sevoflurane greatly enhanced while propofol diminished the ON visual response. Interestingly, the large potentiation of the ON visual response by sevoflurane was found to represent a linear scaling of the encoding mechanism for light intensity. To the contrary, the OFF cortical visual response was depressed by both anaesthetics. The selective depression of the OFF component by sevoflurane could be converted into a robust potentiation by the pharmacological blockade of the ON pathway, suggesting that the temporal order of ON and OFF responses leads to a depression of the latter. This hypothesis agrees with the finding that the enhancement of the ON response was converted into a depression by increasing the frequency of light-pulse stimulation from 0.1 to 1 Hz. Overall, our results support the view that inactivity-dependent modulation of cortical circuits produces an increase in their responsiveness. Among the implications of our findings, the silencing of cortical circuits can boost linearly the cortical responsiveness but with negative impact on their frequency transfer and with a loss of the information content of the sensory signal. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Nothing can be coincidence: synaptic inhibition and plasticity in the cerebellar nuclei

PubMed Central

Pugh, Jason R.; Raman, Indira M.

2009-01-01

Many cerebellar neurons fire spontaneously, generating 10–100 action potentials per second even without synaptic input. This high basal activity correlates with information-coding mechanisms that differ from those of cells that are quiescent until excited synaptically. For example, in the deep cerebellar nuclei, Hebbian patterns of coincident synaptic excitation and postsynaptic firing fail to induce long-term increases in the strength of excitatory inputs. Instead, excitatory synaptic currents are potentiated by combinations of inhibition and excitation that resemble the activity of Purkinje and mossy fiber afferents that is predicted to occur during cerebellar associative learning tasks. Such results indicate that circuits with intrinsically active neurons have rules for information transfer and storage that distinguish them from other brain regions. PMID:19178955

Factors Underlying Bursting Behavior in a Network of Cultured Hippocampal Neurons Exposed to Zero Magnesium

PubMed Central

Mangan, Patrick S.; Kapur, Jaideep

2010-01-01

Factors contributing to reduced magnesium-induced neuronal action potential bursting were investigated in primary hippocampal cell culture at high and low culture density. In nominally zero external magnesium medium, pyramidal neurons from high-density cultures produced recurrent spontaneous action potential bursts superimposed on prolonged depolarizations. These bursts were partially attenuated by the NMDA receptor antagonist D-APV. Pharmacological analysis of miniature excitatory postsynaptic currents (EPSCs) revealed 2 components: one sensitive to D-APV and another to the AMPA receptor antagonist DNQX. The components were kinetically distinct. Participation of NMDA receptors in reduced magnesium-induced synaptic events was supported by the localization of the NR1 subunit of the NMDA receptor with the presynaptic vesicular protein synaptophysin. Presynaptically, zero magnesium induced a significant increase in EPSC frequency likely attributable to increased neuronal hyperexcitability induced by reduced membrane surface charge screening. Mean quantal content was significantly increased in zero magnesium. Cells from low-density cultures did not exhibit action potential bursting in zero magnesium but did show increased EPSC frequency. Low-density neurons had less synaptophysin immunofluorescence and fewer active synapses as determined by FM1-43 analysis. These results demonstrate that multiple factors are involved in network bursting. Increased probability of transmitter release presynaptically, enhanced NMDA receptor-mediated excitability postsynaptically, and extent of neuronal interconnectivity contribute to initiation and maintenance of elevated network excitability. PMID:14534286

Conditional Lineage Ablation to Model Human Diseases

NASA Astrophysics Data System (ADS)

Lee, Paul; Morley, Gregory; Huang, Qian; Fischer, Avi; Seiler, Stephanie; Horner, James W.; Factor, Stephen; Vaidya, Dhananjay; Jalife, Jose; Fishman, Glenn I.

1998-09-01

Cell loss contributes to the pathogenesis of many inherited and acquired human diseases. We have developed a system to conditionally ablate cells of any lineage and developmental stage in the mouse by regulated expression of the diphtheria toxin A (DTA) gene by using tetracycline-responsive promoters. As an example of this approach, we targeted expression of DTA to the hearts of adult mice to model structural abnormalities commonly observed in human cardiomyopathies. Induction of DTA expression resulted in cell loss, fibrosis, and chamber dilatation. As in many human cardiomyopathies, transgenic mice developed spontaneous arrhythmias in vivo, and programmed electrical stimulation of isolated-perfused transgenic hearts demonstrated a strikingly high incidence of spontaneous and inducible ventricular tachycardia. Affected mice showed marked perturbations of cardiac gap junction channel expression and localization, including a subset with disorganized epicardial activation patterns as revealed by optical action potential mapping. These studies provide important insights into mechanisms of arrhythmogenesis and suggest that conditional lineage ablation may have wide applicability for studies of disease pathogenesis.

Facilitation effect of observed motor deviants in a cooperative motor task: Evidence for direct perception of social intention in action.

PubMed

Quesque, François; Delevoye-Turrell, Yvonne; Coello, Yann

2016-01-01

Spatiotemporal parameters of voluntary motor action may help optimize human social interactions. Yet it is unknown whether individuals performing a cooperative task spontaneously perceive subtly informative social cues emerging through voluntary actions. In the present study, an auditory cue was provided through headphones to an actor and a partner who faced each other. Depending on the pitch of the auditory cue, either the actor or the partner were required to grasp and move a wooden dowel under time constraints from a central to a lateral position. Before this main action, the actor performed a preparatory action under no time constraint, consisting in placing the wooden dowel on the central location when receiving either a neutral ("prêt"-ready) or an informative auditory cue relative to who will be asked to perform the main action (the actor: "moi"-me, or the partner: "lui"-him). Although the task focused on the main action, analysis of motor performances revealed that actors performed the preparatory action with longer reaction times and higher trajectories when informed that the partner would be performing the main action. In this same condition, partners executed the main actions with shorter reaction times and lower velocities, despite having received no previous informative cues. These results demonstrate that the mere observation of socially driven motor actions spontaneously influences the low-level kinematics of voluntary motor actions performed by the observer during a cooperative motor task. These findings indicate that social intention can be anticipated from the mere observation of action patterns.

Memory in a fractional-order cardiomyocyte model alters properties of alternans and spontaneous activity

NASA Astrophysics Data System (ADS)

Comlekoglu, T.; Weinberg, S. H.

2017-09-01

Cardiac memory is the dependence of electrical activity on the prior history of one or more system state variables, including transmembrane potential (Vm), ionic current gating, and ion concentrations. While prior work has represented memory either phenomenologically or with biophysical detail, in this study, we consider an intermediate approach of a minimal three-variable cardiomyocyte model, modified with fractional-order dynamics, i.e., a differential equation of order between 0 and 1, to account for history-dependence. Memory is represented via both capacitive memory, due to fractional-order Vm dynamics, that arises due to non-ideal behavior of membrane capacitance; and ionic current gating memory, due to fractional-order gating variable dynamics, that arises due to gating history-dependence. We perform simulations for varying Vm and gating variable fractional-orders and pacing cycle length and measure action potential duration (APD) and incidence of alternans, loss of capture, and spontaneous activity. In the absence of ionic current gating memory, we find that capacitive memory, i.e., decreased Vm fractional-order, typically shortens APD, suppresses alternans, and decreases the minimum cycle length (MCL) for loss of capture. However, in the presence of ionic current gating memory, capacitive memory can prolong APD, promote alternans, and increase MCL. Further, we find that reduced Vm fractional order (typically less than 0.75) can drive phase 4 depolarizations that promote spontaneous activity. Collectively, our results demonstrate that memory reproduced by a fractional-order model can play a role in alternans formation and pacemaking, and in general, can greatly increase the range of electrophysiological characteristics exhibited by a minimal model.

Membrane currents underlying activity in frog sinus venosus

PubMed Central

Brown, Hilary F.; Giles, Wayne; Noble, Susan J.

1977-01-01

1. The spontaneous electrical activity of small strips of muscle from the sinus venosus region of the heart of Rana catesbeiana was investigated using the double sucrose gap technique. The voltage clamp was used to record the ionic currents underlying the pace-maker depolarization and the action potential. 2. The records of spontaneous electrical activity are very similar to those obtained from the sinus venosus using micro-electrodes. Moreover, the pace-maker activity is almost completely insensitive to tetrodotoxin (TTX) at 2·0 × 10-6 g/ml., which suggests that the pace-maker responses can be classified as primary, as opposed to follower pacing. 3. In response to short rectangular depolarizing voltage clamp pulses, only one inward current is activated. This current is almost completely insensitive to TTX but can be blocked by manganese ions. It appears, therefore, to be equivalent to the slow inward (Ca2+/Na+) current, Isi, of other cardiac tissues. The threshold for Isi is near to the maximum diastolic potential, indicating that it must be activated during the pace-maker depolarization. 4. Interruption of the normal pace-maker depolarization by rapid activation of the voltage clamp circuit reveals the time-dependent decay of outward current. This current reverses between -75 and -90 mV and, therefore, is probably carried mainly by potassium ions. 5. Outward current decay is not a simple exponential, and Hodgkin—Huxley analysis suggests that two distinct components of outward current may be present. One of these is activated in the potential range of the pace-maker depolarization and the other at more positive potentials. Both outward currents reach full, steady-state activation at about zero mV, i.e. within the `plateau' range of the sinus action potential. 6. These results are compared with other recently published voltage clamp data from the rabbit sino—atrial node. 7. A hypothesis for the generation of pace-maker activity is presented which involves (i) decay of outward current and (ii) activation of the slow inward current, Isi. PMID:303699

Phase seeding of a terahertz quantum cascade laser

PubMed Central

Oustinov, Dimitri; Jukam, Nathan; Rungsawang, Rakchanok; Madéo, Julien; Barbieri, Stefano; Filloux, Pascal; Sirtori, Carlo; Marcadet, Xavier; Tignon, Jérôme; Dhillon, Sukhdeep

2010-01-01

The amplification of spontaneous emission is used to initiate laser action. As the phase of spontaneous emission is random, the phase of the coherent laser emission (the carrier phase) will also be random each time laser action begins. This prevents phase-resolved detection of the laser field. Here, we demonstrate how the carrier phase can be fixed in a semiconductor laser: a quantum cascade laser (QCL). This is performed by injection seeding a QCL with coherent terahertz pulses, which forces laser action to start on a fixed phase. This permits the emitted laser field to be synchronously sampled with a femtosecond laser beam, and measured in the time domain. We observe the phase-resolved buildup of the laser field, which can give insights into the laser dynamics. In addition, as the electric field oscillations are directly measured in the time domain, QCLs can now be used as sources for time-domain spectroscopy. PMID:20842195

Single CA3 pyramidal cells trigger sharp waves in vitro by exciting interneurones.

PubMed

Bazelot, Michaël; Teleńczuk, Maria T; Miles, Richard

2016-05-15

The CA3 hippocampal region generates sharp waves (SPW), a population activity associated with neuronal representations. The synaptic mechanisms responsible for the generation of these events still require clarification. Using slices maintained in an interface chamber, we found that the firing of single CA3 pyramidal cells triggers SPW like events at short latencies, similar to those for the induction of firing in interneurons. Multi-electrode records from the CA3 stratum pyramidale showed that pyramidal cells triggered events consisting of putative interneuron spikes followed by field IPSPs. SPW fields consisted of a repetition of these events at intervals of 4-8 ms. Although many properties of induced and spontaneous SPWs were similar, the triggered events tended to be initiated close to the stimulated cell. These data show that the initiation of SPWs in vitro is mediated via pyramidal cell synapses that excite interneurons. They do not indicate why interneuron firing is repeated during a SPW. Sharp waves (SPWs) are a hippocampal population activity that has been linked to neuronal representations. We show that SPWs in the CA3 region of rat hippocampal slices can be triggered by the firing of single pyramidal cells. Single action potentials in almost one-third of pyramidal cells initiated SPWs at latencies of 2-5 ms with probabilities of 0.07-0.76. Initiating pyramidal cells evoked field IPSPs (fIPSPs) at similar latencies when SPWs were not initiated. Similar spatial profiles for fIPSPs and middle components of SPWs suggested that SPW fields reflect repeated fIPSPs. Multiple extracellular records showed that the initiated SPWs tended to start near the stimulated pyramidal cell, whereas spontaneous SPWs could emerge at multiple sites. Single pyramidal cells could initiate two to six field IPSPs with distinct amplitude distributions, typically preceeded by a short-duration extracellular action potential. Comparison of these initiated fields with spontaneously occurring inhibitory field motifs allowed us to identify firing in different interneurones during the spread of SPWs. Propagation away from an initiating pyramidal cell was typically associated with the recruitment of interneurones and field IPSPs that were not activated by the stimulated pyramidal cell. SPW fields initiated by single cells were less variable than spontaneous events, suggesting that more stereotyped neuronal ensembles were activated, although neither the spatial profiles of fields, nor the identities of interneurone firing were identical for initiated events. The effects of single pyramidal cell on network events are thus mediated by different sequences of interneurone firing. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Transcranial magnetic stimulation and potential cortical and trigeminothalamic mechanisms in migraine

PubMed Central

Andreou, Anna P.; Holland, Philip R.; Akerman, Simon; Summ, Oliver; Fredrick, Joe

2016-01-01

Abstract A single pulse of transcranial magnetic stimulation has been shown to be effective for the acute treatment of migraine with and without aura. Here we aimed to investigate the potential mechanisms of action of transcranial magnetic stimulation, using a transcortical approach, in preclinical migraine models. We tested the susceptibility of cortical spreading depression, the experimental correlate of migraine aura, and further evaluated the response of spontaneous and evoked trigeminovascular activity of second order trigemontothalamic and third order thalamocortical neurons in rats. Single pulse transcranial magnetic stimulation significantly inhibited both mechanical and chemically-induced cortical spreading depression when administered immediately post-induction in rats, but not when administered preinduction, and when controlled by a sham stimulation. Additionally transcranial magnetic stimulation significantly inhibited the spontaneous and evoked firing rate of third order thalamocortical projection neurons, but not second order neurons in the trigeminocervical complex, suggesting a potential modulatory effect that may underlie its utility in migraine. In gyrencephalic cat cortices, when administered post-cortical spreading depression, transcranial magnetic stimulation blocked the propagation of cortical spreading depression in two of eight animals. These results are the first to demonstrate that cortical spreading depression can be blocked in vivo using single pulse transcranial magnetic stimulation and further highlight a novel thalamocortical modulatory capacity that may explain the efficacy of magnetic stimulation in the treatment of migraine with and without aura. PMID:27246325

Phenytoin attenuates the hyper-exciting neurotransmission in cultured embryonic cortical neurons.

PubMed

Chou, Ming-Yi; Lee, Chun-Yao; Liou, Horng-Huei; Pan, Chien-Yuan

2014-08-01

Phenytoin is an effective anti-epileptic drug that inhibits Na(+) channel activities; however, how phenytoin modulates synaptic transmission to soothe epileptic symptoms is not clear. To characterize the effects of phenytoin regulation on neurotransmission, we studied the electrophysical properties of cultured embryonic cortical neurons. Phenytoin inhibited the inward Na(+) current in a dose-dependent manner with an IC50 of 16.8 μM, and at 100 μM, the inhibitory effect of phenytoin on the Na(+) current was proportional to the frequency applied. In cultured neurons, phenytoin significantly decreased the action potential firing rate and the peak potential. To study the effect of phenytoin in neurotransmission, we measured the Ca(2+) responses from stimulated target neurons and their neighboring neurons. Phenytoin significantly suppressed the Ca(2+) responses evoked by strong stimulations in the target and neighboring neurons, and exerted a decreased inhibitory effect under moderate stimulation. Picrotoxin, a GABAA receptor antagonist, enhanced the recorded spontaneous excitatory postsynaptic current activities. After picrotoxin-induced enhancement, phenytoin had a more pronounced effect on the suppression of the spontaneous hyper-exciting excitatory postsynaptic current (>100 pA), but it only mildly inhibited the general excitatory postsynaptic current. Our results demonstrate that phenytoin suppresses the efficacy of neurotransmission especially for the high-frequency stimulation by reducing the Na(+) channel activity and can potentially alleviate epileptiform activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Use of Psychodrama Action Techniques in a Race Relations Class

ERIC Educational Resources Information Center

Kranz, Peter L.; Ramirez, Sylvia Z.; Lund, Nick L.

2007-01-01

This article describes psychodrama action techniques that were effectively implemented in a university-level race relations course. Essential elements of these techniques included acting out and critical self-examination of the individual's personal beliefs. In a semi-structured class format in which uncensored spontaneity was stressed, students…

No Evidence for Ionotropic Pheromone Transduction in the Hawkmoth Manduca sexta.

PubMed

Nolte, Andreas; Gawalek, Petra; Koerte, Sarah; Wei, HongYing; Schumann, Robin; Werckenthin, Achim; Krieger, Jürgen; Stengl, Monika

2016-01-01

Insect odorant receptors (ORs) are 7-transmembrane receptors with inverse membrane topology. They associate with the conserved ion channel Orco. As chaperon, Orco maintains ORs in cilia and, as pacemaker channel, Orco controls spontaneous activity in olfactory receptor neurons. Odorant binding to ORs opens OR-Orco receptor ion channel complexes in heterologous expression systems. It is unknown, whether this also occurs in vivo. As an alternative to this ionotropic transduction, experimental evidence is accumulating for metabotropic odor transduction, implicating that insect ORs couple to G-proteins. Resulting second messengers gate various ion channels. They generate the sensillum potential that elicits phasic-tonic action potentials (APs) followed by late, long-lasting pheromone responses. Because it is still unclear how and when Orco opens after odor-OR-binding, we used tip recordings to examine in vivo the effects of the Orco antagonist OLC15 and the amilorides MIA and HMA on bombykal transduction in the hawkmoth Manduca sexta. In contrast to OLC15 both amilorides decreased the pheromone-dependent sensillum potential amplitude and the frequency of the phasic AP response. Instead, OLC15 decreased spontaneous activity, increased latencies of phasic-, and decreased frequencies of late, long-lasting pheromone responses Zeitgebertime-dependently. Our results suggest no involvement for Orco in the primary transduction events, in contrast to amiloride-sensitive channels. Instead of an odor-gated ionotropic receptor, Orco rather acts as a voltage- and apparently second messenger-gated pacemaker channel controlling the membrane potential and hence threshold and kinetics of the pheromone response.

High glucose increases action potential firing of catecholamine neurons in the nucleus of the solitary tract by increasing spontaneous glutamate inputs.

PubMed

Roberts, Brandon L; Zhu, Mingyan; Zhao, Huan; Dillon, Crystal; Appleyard, Suzanne M

2017-09-01

Glucose is a crucial substrate essential for cell survival and function. Changes in glucose levels impact neuronal activity and glucose deprivation increases feeding. Several brain regions have been shown to respond to glucoprivation, including the nucleus of the solitary tract (NTS) in the brain stem. The NTS is the primary site in the brain that receives visceral afferent information from the gastrointestinal tract. The catecholaminergic (CA) subpopulation within the NTS modulates many homeostatic functions including cardiovascular reflexes, respiration, food intake, arousal, and stress. However, it is not known if they respond to changes in glucose. Here we determined whether NTS-CA neurons respond to changes in glucose concentration and the mechanism involved. We found that decreasing glucose concentrations from 5 mM to 2 mM to 1 mM, significantly decreased action potential firing in a cell-attached preparation, whereas increasing it back to 5 mM increased the firing rate. This effect was dependent on glutamate release from afferent terminals and required presynaptic 5-HT 3 Rs. Decreasing the glucose concentration also decreased both basal and 5-HT 3 R agonist-induced increase in the frequency of spontaneous glutamate inputs onto NTS-CA neurons. Low glucose also blunted 5-HT-induced inward currents in nodose ganglia neurons, which are the cell bodies of vagal afferents. The effect of low glucose in both nodose ganglia cells and in NTS slices was mimicked by the glucokinase inhibitor glucosamine. This study suggests that NTS-CA neurons are glucosensing through a presynaptic mechanism that is dependent on vagal glutamate release, 5-HT 3 R activity, and glucokinase. Copyright © 2017 the American Physiological Society.

A new engineering approach to reveal correlation of physiological change and spontaneous expression from video images

NASA Astrophysics Data System (ADS)

Yang, Fenglei; Hu, Sijung; Ma, Xiaoyun; Hassan, Harnani; Wei, Dongqing

2015-03-01

Spontaneous expression is associated with physiological states, i.e., heart rate, respiration, oxygen saturation (SpO2%), and heart rate variability (HRV). There have yet not sufficient efforts to explore correlation of physiological change and spontaneous expression. This study aims to study how spontaneous expression is associated with physiological changes with an approved protocol or through the videos provided from Denver Intensity of Spontaneous Facial Action Database. Not like a posed expression, motion artefact in spontaneous expression is one of evitable challenges to be overcome in the study. To obtain a physiological signs from a region of interest (ROI), a new engineering approach is being developed with an artefact-reduction method consolidated 3D active appearance model (AAM) based track, affine transformation based alignment with opto-physiological mode based imaging photoplethysmography. Also, a statistical association spaces is being used to interpret correlation of spontaneous expressions and physiological states including their probability densities by means of Gaussian Mixture Model. The present work is revealing a new avenue of study associations of spontaneous expressions and physiological states with its prospect of applications on physiological and psychological assessment.

Mechanism of soman-induced contractions in canine tracheal smooth muscle. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adler, M.; Moore, D.H.; Filbert, M.G.

1992-12-31

The actions of the irreversible organophosphorus cholinesterase (ChE) inhibitor soman were investigated on canine trachea smooth muscle in vitro. Concentrations of soman > or - 1 nM increased the amplitude and decay of contractions elicited by electric field stimulation. The effect on decay showed a marked dependence on stimulation frequency, undergoing a 2.4-fold increase between 3 and 60 Hz. Soman also potentiated tensions due to bath applied acetylcholine (ACh). Little or no potentiation was observed for contractions elicited by carbamylcholine, an agonist that is not hydrolyzed by ChE. Concentration of soman > or - 3 nM led to the appearancemore » of sustained contractures. These contractures developed with a delayed onset and were well correlated with ChE activity. Alkylation of muscarinic receptors by propylbenzilylcholine mustard antagonized the actions of soman on both spontaneous and electrically-evoked muscle contractions. The results are consistent with a mechanism in which the toxic actions of soman are mediated by accumulation of neurally-released ACh secondary to inhibition of ChE activity. An important factor in this accumulation is suggested to be the buffering effect of the muscarinic receptors on the efflux of ACh from the neuroeffector junction. Tracheal smooth muscle, Cholinesterase inhibitors, Muscarinic receptor, Soman, Organophosphate.« less

Carbon nanotube multi-electrode array chips for noninvasive real-time measurement of dopamine, action potentials, and postsynaptic potentials.

PubMed

Suzuki, Ikuro; Fukuda, Mao; Shirakawa, Keiichi; Jiko, Hideyasu; Gotoh, Masao

2013-11-15

Multi-electrode arrays (MEAs) can be used for noninvasive, real-time, and long-term recording of electrophysiological activity and changes in the extracellular chemical microenvironment. Neural network organization, neuronal excitability, synaptic and phenotypic plasticity, and drug responses may be monitored by MEAs, but it is still difficult to measure presynaptic activity, such as neurotransmitter release, from the presynaptic bouton. In this study, we describe the development of planar carbon nanotube (CNT)-MEA chips that can measure both the release of the neurotransmitter dopamine as well as electrophysiological responses such as field postsynaptic potentials (fPSPs) and action potentials (APs). These CNT-MEA chips were fabricated by electroplating the indium-tin oxide (ITO) microelectrode surfaces. The CNT-plated ITO electrode exhibited electrochemical response, having much higher current density compared with the bare ITO electrode. Chronoamperometric measurements using these CNT-MEA chips detected dopamine at nanomolar concentrations. By placing mouse striatal brain slices on the CNT-MEA chip, we successfully measured synaptic dopamine release from spontaneous firings with a high S/N ratio of 62. Furthermore, APs and fPSPs were measured from cultured hippocampal neurons and slices with high temporal resolution and a 100-fold greater S/N ratio. Our CNT-MEA chips made it possible to measure neurotransmitter dopamine (presynaptic activities), postsynaptic potentials, and action potentials, which have a central role in information processing in the neuronal network. CNT-MEA chips could prove useful for in vitro studies of stem cell differentiation, drug screening and toxicity, synaptic plasticity, and pathogenic processes involved in epilepsy, stroke, and neurodegenerative diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

Short- and medium-term plasticity associated with augmenting responses in cortical slabs and spindles in intact cortex of cats in vivo

PubMed Central

Timofeev, Igor; Grenier, François; Bazhenov, Maxim; Houweling, Arthur R; Sejnowski, Terrence J; Steriade, Mircea

2002-01-01

Plastic changes in the synaptic responsiveness of neocortical neurones, which occur after rhythmic stimuli within the frequency range of sleep spindles (10 Hz), were investigated in isolated neocortical slabs and intact cortex of anaesthetized cats by means of single, dual and triple simultaneous intracellular recordings in conjunction with recordings of local field potential responses. In isolated cortical slabs (10 mm long, 6 mm wide and 4–5 mm deep), augmenting responses to pulse-trains at 10 Hz (responses with growing amplitudes from the second stimulus in a train) were elicited only by relatively high-intensity stimuli. At low intensities, responses were decremental. The largest augmenting responses were evoked in neurones located close to the stimulation site. Quantitative analyses of the number of action potentials and the amplitude and area of depolarization during augmenting responses in a population of neurones recorded from slabs showed that the most dramatic increases in the number of spikes with successive stimuli, and the greatest increase in depolarization amplitude, were found in conventional fast-spiking (FS) neurones. The largest increase in the area of depolarization was found in regular-spiking (RS) neurones. Dual intracellular recordings from a pair of FS and RS neurones in the slab revealed more action potentials in the FS neurone during augmenting responses and a significant increase in the depolarization area of the RS neurone that was dependent on the firing of the FS neurone. Self-sustained seizures could occur in the slab after rhythmic stimuli at 10 Hz. In the intact cortex, repeated sequences of stimuli generating augmenting responses or spontaneous spindles could induce an increased synaptic responsiveness to single stimuli, which lasted for several minutes. A similar time course of increased responsiveness was obtained with induction of cellular plasticity. These data suggest that augmenting responses elicited by stimulation, as well as spontaneously occurring spindles, may induce short- and medium-term plasticity of neuronal responses. PMID:12122155

DRG Voltage-Gated Sodium Channel 1.7 Is Upregulated in Paclitaxel-Induced Neuropathy in Rats and in Humans with Neuropathic Pain.

PubMed

Li, Yan; North, Robert Y; Rhines, Laurence D; Tatsui, Claudio Esteves; Rao, Ganesh; Edwards, Denaya D; Cassidy, Ryan M; Harrison, Daniel S; Johansson, Caj A; Zhang, Hongmei; Dougherty, Patrick M

2018-01-31

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect experienced by cancer patients receiving treatment with paclitaxel. The voltage-gated sodium channel 1.7 (Na v 1.7) plays an important role in multiple preclinical models of neuropathic pain and in inherited human pain phenotypes, and its gene expression is increased in dorsal root ganglia (DRGs) of paclitaxel-treated rats. Hence, the potential of change in the expression and function of Na v 1.7 protein in DRGs from male rats with paclitaxel-related CIPN and from male and female humans with cancer-related neuropathic pain was tested here. Double immunofluorescence in CIPN rats showed that Na v 1.7 was upregulated in small DRG neuron somata, especially those also expressing calcitonin gene-related peptide (CGRP), and in central processes of these cells in the superficial spinal dorsal horn. Whole-cell patch-clamp recordings in rat DRG neurons revealed that paclitaxel induced an enhancement of ProTx II (a selective Na v 1.7 channel blocker)-sensitive sodium currents. Bath-applied ProTx II suppressed spontaneous action potentials in DRG neurons occurring in rats with CIPN, while intrathecal injection of ProTx II significantly attenuated behavioral signs of CIPN. Complementarily, DRG neurons isolated from segments where patients had a history of neuropathic pain also showed electrophysiological and immunofluorescence results indicating an increased expression of Na v 1.7 associated with spontaneous activity. Na v 1.7 was also colocalized in human cells expressing transient receptor potential vanilloid 1 and CGRP. Furthermore, ProTx II decreased firing frequency in human DRGs with spontaneous action potentials. This study suggests that Na v 1.7 may provide a potential new target for the treatment of neuropathic pain, including chemotherapy (paclitaxel)-induced neuropathic pain. SIGNIFICANCE STATEMENT This work demonstrates that the expression and function of the voltage-gated sodium channel Na v 1.7 are increased in a preclinical model of chemotherapy-induced peripheral neuropathy (CIPN), the most common treatment-limiting side effect of all the most common anticancer therapies. This is key as gain-of-function mutations in human Na v 1.7 recapitulate both the distribution and pain percept as shown by CIPN patients. This work also shows that Na v 1.7 is increased in human DRG neurons only in dermatomes where patients are experiencing acquired neuropathic pain symptoms. This work therefore has major translational impact, indicating an important novel therapeutic avenue for neuropathic pain as a class. Copyright © 2018 the authors 0270-6474/18/381124-13$15.00/0.

Adaptation, perceptual learning, and plasticity of brain functions.

PubMed

Horton, Jonathan C; Fahle, Manfred; Mulder, Theo; Trauzettel-Klosinski, Susanne

2017-03-01

The capacity for functional restitution after brain damage is quite different in the sensory and motor systems. This series of presentations highlights the potential for adaptation, plasticity, and perceptual learning from an interdisciplinary perspective. The chances for restitution in the primary visual cortex are limited. Some patterns of visual field loss and recovery after stroke are common, whereas others are impossible, which can be explained by the arrangement and plasticity of the cortical map. On the other hand, compensatory mechanisms are effective, can occur spontaneously, and can be enhanced by training. In contrast to the human visual system, the motor system is highly flexible. This is based on special relationships between perception and action and between cognition and action. In addition, the healthy adult brain can learn new functions, e.g. increasing resolution above the retinal one. The significance of these studies for rehabilitation after brain damage will be discussed.

Safinamide Differentially Modulates In Vivo Glutamate and GABA Release in the Rat Hippocampus and Basal Ganglia.

PubMed

Morari, Michele; Brugnoli, Alberto; Pisanò, Clarissa Anna; Novello, Salvatore; Caccia, Carla; Melloni, Elsa; Padoani, Gloria; Vailati, Silvia; Sardina, Marco

2018-02-01

Safinamide has been recently approved as an add-on to levodopa therapy for Parkinson disease. In addition to inhibiting monoamine oxidase type B, it blocks sodium channels and modulates glutamate (Glu) release in vitro. Since this property might contribute to the therapeutic action of the drug, we undertook the present study to investigate whether safinamide inhibits Glu release also in vivo and whether this effect is consistent across different brain areas and is selective for glutamatergic neurons. To this aim, in vivo microdialysis was used to monitor the spontaneous and veratridine-induced Glu and GABA release in the hippocampus and basal ganglia of naive, awake rats. Brain levels of safinamide were measured as well. To shed light on the mechanisms underlying the effect of safinamide, sodium currents were measured by patch-clamp recording in rat cortical neurons. Safinamide maximally inhibited the veratridine-induced Glu and GABA release in hippocampus at 15 mg/kg, which reached free brain concentrations of 1.89-1.37 µ M. This dose attenuated veratridine-stimulated Glu (but not GABA) release in subthalamic nucleus, globus pallidus, and substantia nigra reticulata, but not in striatum. Safinamide was ineffective on spontaneous neurotransmitter release. In vitro, safinamide inhibited sodium channels, showing a greater affinity at depolarized (IC 50 = 8 µ M) than at resting (IC 50 = 262 µ M) potentials. We conclude that safinamide inhibits in vivo Glu release from stimulated nerve terminals, likely via blockade of sodium channels at subpopulations of neurons with specific firing patterns. These data are consistent with the anticonvulsant and antiparkinsonian actions of safinamide and provide support for the nondopaminergic mechanism of its action. Copyright © 2018 The Author(s).

Simulating an Enactment Effect: Pronouns Guide Action Simulation during Narrative Comprehension

ERIC Educational Resources Information Center

Ditman, Tali; Brunye, Tad T.; Mahoney, Caroline R.; Taylor, Holly A.

2010-01-01

Recent research has suggested that reading involves the mental simulation of events and actions described in a text. It is possible however that previous findings did not tap into processes engaged during natural reading but rather those triggered by task demands. The present study examined whether readers spontaneously mentally simulate the…

Transplantation of cryopreserved human umbilical cord blood mononuclear cells does not induce sustained recovery after experimental stroke in spontaneously hypertensive rats

PubMed Central

Weise, Gesa; Lorenz, Marlene; Pösel, Claudia; Maria Riegelsberger, Ute; Störbeck, Veronika; Kamprad, Manja; Kranz, Alexander; Wagner, Daniel-Christoph; Boltze, Johannes

2014-01-01

Previous studies have highlighted the enormous potential of cell-based therapies for stroke not only to prevent ischemic brain damage, but also to amplify endogenous repair processes. Considering its widespread availability and low immunogenicity human umbilical cord blood (HUCB) is a particularly attractive stem cell source. Our goal was to investigate the neurorestorative potential of cryopreserved HUCB mononuclear cells (MNC) after permanent middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats (SHR). Human umbilical cord blood MNC or vehicle solution was administered intravenously 24 hours after MCAO. Experimental groups were as follows: (1) quantitative polymerase chain reaction (PCR) of host-derived growth factors up to 48 hours after stroke; (2) immunohistochemical analysis of astroglial scarring; (3) magnetic resonance imaging (MRI) and weekly behavioral tests for 2 months after stroke. Long-term functional outcome and lesion development on MRI were not beneficially influenced by HUCB MNC therapy. Furthermore, HUCB MNC treatment did not change local growth factor levels and glial scarring extent. In summary, we could not demonstrate neurorestorative properties of HUCB MNC after stroke in SHR. Our results advise caution regarding a prompt translation of cord blood therapy into clinical stroke trials as long as deepened knowledge about its precise modes of action is missing. PMID:24169850

Crossed motor innervation of the base of human tongue

PubMed Central

Jordan, Amy S.; Nicholas, Christian L.; Cori, Jennifer M.; Semmler, John G.; Trinder, John

2015-01-01

Muscle fibers of the genioglossus (GG) form the bulk of the muscle mass at the base of the tongue. The motor control of the tongue is critical for vocalization, feeding, and breathing. Our goal was to assess the patterns of motor innervation of GG single motor units (SMUs) in humans. Simultaneous monopolar recordings were obtained from four sites in the base of the tongue bilaterally at two antero-posterior levels from 16 resting, awake, healthy adult males, who wore a face mask with airway pressure and airflow sensors. We analyzed 69 data segments in which at least one lead contained large action potentials generated by an SMU. Such potentials served as triggers for spike-triggered averaging (STA) of signals recorded from the other three sites. Spontaneous activity of the SMUs was classified as inspiratory modulated, expiratory modulated, or tonic. Consistent with the antero-posterior orientation of GG fibers, 44 STAs (77%) recorded ipsilateral to the trigger yielded sharp action potentials with a median amplitude of 52 μV [interquartile range (IQR): 25–190] that were time shifted relative to the trigger by about 1 ms. Notably, 48% of recordings on the side opposite to the trigger also yielded sharp action potentials. Of those, 17 (29%) had a median amplitude of 63 μV (IQR: 39–96), and most were generated by tonic SMUs. Thus a considerable proportion of GG muscle fibers receive a crossed motor innervation. Crossed innervation may help ensure symmetry and stability of tongue position and movements under normal conditions and following injury or degenerative changes affecting the tongue. PMID:25855691

Autocrine feedback inhibition of plateau potentials terminates phasic bursts in magnocellular neurosecretory cells of the rat supraoptic nucleus

PubMed Central

Brown, Colin H; Bourque, Charles W

2004-01-01

Phasic activity in magnocellular neurosecretory cells is characterized by alternating periods of activity (bursts) and silence. During phasic bursts, action potentials are superimposed on plateau potentials that are generated by summation of depolarizing after-potentials. Dynorphin is copackaged in vasopressin neurosecretory vesicles that are exocytosed from magnocellular neurosecretory cell dendrites and terminals, and both peptides have been implicated in the generation of phasic activity. Here we show that somato-dendritic dynorphin release terminates phasic bursts by autocrine inhibition of plateau potentials in magnocellular neurosecretory cells recorded intracellularly from hypothalamic explants using sharp electrodes. Conditioning spike trains caused an activity-dependent reduction of depolarizing after-potential amplitude that was partially reversed by α-latrotoxin (which depletes neurosecretory vesicles) and by nor-binaltorphimine (κ-opioid receptor antagonist), but not by an oxytocin/vasopressin receptor antagonist or a μ-opioid receptor antagonist, indicating that activity-dependent inhibition of depolarizing after-potentials requires exocytosis of an endogenous κ-opioid peptide. κ-Opioid inhibition of depolarizing after-potentials was not mediated by actions on evoked after-hyperpolarizations since these were not affected by κ-opioid receptor agonists or antagonists. Evoked bursts were prolonged by antagonism of κ-opioid receptors with nor-binaltorphimine and by depletion of neurosecretory vesicles by α-latrotoxin, becoming everlasting in ∼50% of cells. Finally, spontaneously active neurones exposed to nor-binaltorphimine switched from phasic to continuous firing as plateau potentials became non-inactivating. Thus, dynorphin coreleased with vasopressin generates phasic activity through activity-dependent feedback inhibition of plateau potentials in magnocellular neurosecretory cells. PMID:15107473

Computational analysis of the human sinus node action potential: model development and effects of mutations

PubMed Central

Fabbri, Alan; Fantini, Matteo; Wilders, Ronald

2017-01-01

Key points We constructed a comprehensive mathematical model of the spontaneous electrical activity of a human sinoatrial node (SAN) pacemaker cell, starting from the recent Severi–DiFrancesco model of rabbit SAN cells.Our model is based on electrophysiological data from isolated human SAN pacemaker cells and closely matches the action potentials and calcium transient that were recorded experimentally.Simulated ion channelopathies explain the clinically observed changes in heart rate in corresponding mutation carriers, providing an independent qualitative validation of the model.The model shows that the modulatory role of the ‘funny current’ (I f) in the pacing rate of human SAN pacemaker cells is highly similar to that of rabbit SAN cells, despite its considerably lower amplitude.The model may prove useful in the design of experiments and the development of heart‐rate modulating drugs. Abstract The sinoatrial node (SAN) is the normal pacemaker of the mammalian heart.  Over several decades, a large amount of data on the ionic mechanisms underlying the spontaneous electrical activity of SAN pacemaker cells has been obtained, mostly in experiments on single cells isolated from rabbit SAN. This wealth of data has allowed the development of mathematical models of the electrical activity of rabbit SAN pacemaker cells. The present study aimed to construct a comprehensive model of the electrical activity of a human SAN pacemaker cell using recently obtained electrophysiological data from human SAN pacemaker cells.  We based our model on the recent Severi–DiFrancesco model of a rabbit SAN pacemaker cell. The action potential and calcium transient of the resulting model are close to the experimentally recorded values. The model has a much smaller ‘funny current’ (I f) than do rabbit cells, although its modulatory role is highly similar. Changes in pacing rate upon the implementation of mutations associated with sinus node dysfunction agree with the clinical observations. This agreement holds for both loss‐of‐function and gain‐of‐function mutations in the HCN4, SCN5A and KCNQ1 genes, underlying ion channelopathies in I f, fast sodium current and slow delayed rectifier potassium current, respectively. We conclude that our human SAN cell model can be a useful tool in the design of experiments and the development of drugs that aim to modulate heart rate. PMID:28185290

Spontaneous voltage and current fluctuations in tissue cultured mouse dorsal root ganglion cells.

PubMed

Mathers, D A; Barker, J L

1984-02-13

Fetal mouse dorsal root ganglion (DRG) neurons were maintained in primary dissociated cell culture for periods of 7 days to 3 months. Intracellular recordings from these cells revealed the presence of spontaneous subthreshold potentials in 101/177 neurons studied. When measured at the resting membrane potential, these spontaneous voltage events took two forms: (a) high frequency potential fluctuations several millivolts in peak-to-peak amplitude and (b) small, discrete hyperpolarizations. Neurons exhibiting either type of event were designated as 'active' DRG cells. No spontaneous potentials were seen in DRG cells hyperpolarized to membrane voltages more negative than -64 +/- 11.5 mV (n = 5 cells). Under voltage-clamp conditions, the subthreshold potentials of active DRG cells were replaced by fluctuations in outward current. The power spectral density, S(f) of these current fluctuations was approximated by an equation of the form S(f) = (S(o)/[1 + (f/fc) alpha] where 2 less than or equal to a less than or equal to 3 and the half-power frequency fc = 11.3 +/- 3.1 Hz at 23 degrees C (n = 17 cells). The spontaneous voltage fluctuations of active DRG cells were abolished in Ca2+-free saline, and of the divalent metal cations Sr2+, Mg2+, Ba2+, Co2+ and Mn2+, only Sr2+ could substitute for Ca2+ in the maintenance of this activity. Tetraethylammonium ions (1-10 mM) reversibly blocked the spontaneous potentials, while caffeine (10 mM) increased the frequency of these events. The spontaneous voltage fluctuations were not dependent on the presence of spinal cord neurons in the culture plate, and they were also observed in cultured DRG cells derived from adult mice.

Spontaneous Ion Depletion and Accumulation Phenomena Induced by Imbibition through Permselective Medium

NASA Astrophysics Data System (ADS)

Lee, Hyomin; Jung, Yeonsu; Park, Sungmin; Kim, Ho-Young; Kim, Sung Jae

2016-11-01

Generally, an ion depletion region near a permselective medium is induced by predominant ion flux through the medium. External electric field or hydraulic pressure has been reported as the driving forces. Among these driving forces, an imbibition through the nanoporous medium was chosen as the mechanism to spontaneously generate the ion depletion region. The water-absorbing process leads to the predominant ion flux so that the spontaneous formation of the ion depletion zone is expected even if there are no additional driving forces except for the inherent capillary action. In this presentation, we derived the analytical solutions using perturbation method and asymptotic analysis for the spontaneous phenomenon. Using the analysis, we found that there is also spontaneous accumulation regime depending on the mobility of dissolved electrolytic species. Therefore, the rigorous analysis of the spontaneous ion depletion and accumulation phenomena would provide a key perspective for the control of ion transportation in nanofluidic system such as desalinator, preconcentrator, and energy harvesting device, etc. Samsung Research Funding Center of Samsung Electronics (SRFC-MA1301-02) and BK21 plus program of Creative Research Engineer Development IT, Seoul National University.

Altered GABAA receptor-mediated synaptic transmission disrupts the firing of gonadotropin-releasing hormone neurons in male mice under conditions that mimic steroid abuse

PubMed Central

Penatti, Carlos A A; Davis, Matthew C; Porter, Donna M; Henderson, Leslie P

2010-01-01

Gonadotropin–releasing hormone (GnRH) neurons are the central regulators of reproduction. GABAergic transmission plays a critical role in pubertal activation of pulsatile GnRH secretion. Self-administration of excessive doses of anabolic androgenic steroids (AAS) disrupts reproductive function and may have critical repercussions for pubertal onset in adolescent users. Here, we demonstrate that chronic treatment of adolescent male mice with the AAS, 17α-methyltestosterone (17αMT), significantly decreased action potential frequency in GnRH neurons, reduced the serum gonadotropin levels, and decreased testes mass. AAS treatment did not induce significant changes in GABAA receptor subunit mRNA levels or alter the amplitude or decay kinetics of GABAA receptor-mediated spontaneous postsynaptic currents (sPSC) or tonic currents in GnRH neurons. However, AAS treatment significantly increased action potential frequency in neighboring medial preoptic area (mPOA) neurons and GABAA receptor-mediated sPSC frequency in GnRH neurons. In addition, physical isolation of the more lateral aspects of the mPOA from the medially-localized GnRH neurons abrogated the AAS-induced increase in GABAA receptor-mediated sPSC frequency and the decrease in action potential firing in the GnRH cells. Our results indicate that AAS act predominantly on steroid-sensitive presynaptic neurons within the mPOA to impart significant increases in GABAA receptor-mediated inhibitory tone onto downstream GnRH neurons resulting in diminished activity of these pivotal mediators of reproductive function. These AAS-induced changes in central GABAergic circuits of the forebrain may significantly contribute to the disruptive actions of these drugs on pubertal maturation and the development of reproductive competence in male steroid abusers. PMID:20463213

Numbers can move our hands: a spatial representation effect in digits handwriting.

PubMed

Perrone, Gelsomina; de Hevia, Maria Dolores; Bricolo, Emanuela; Girelli, Luisa

2010-09-01

The interaction between numbers and action-related processes is currently one of the most investigated topics in numerical cognition. The present study contributes to this line of research by investigating, for the first time, the effects of number on an overlearned complex motor plan that does not require explicit lateralised movements or strict spatial constrains: spontaneous handwriting. In particular, we investigated whether the spatial mapping of numbers interferes with the motor planning involved in writing. To this aim, participants' spontaneous handwriting of single digits (Exp. 1) and letters (Exp. 2) was recorded with a digitising tablet. We show that the writing of numbers is characterised by a spatial dislocation of the digits as a function of their magnitude, i.e., small numbers were written leftwards relative to large numbers. In contrast, the writing of letters showed a null or marginal effect with respect to their dislocation on the writing area. These findings show that the automatic mapping of numbers into space interacts with action planning by modulating specific motor parameters in spontaneous handwriting.

Sleep Improves Prospective Remembering by Facilitating Spontaneous-Associative Retrieval Processes

PubMed Central

Diekelmann, Susanne; Wilhelm, Ines; Wagner, Ullrich; Born, Jan

2013-01-01

Memories are of the past but for the future, enabling individuals to implement intended plans and actions at the appropriate time. Prospective memory is the specific ability to remember and execute an intended behavior at some designated point in the future. Although sleep is well-known to benefit the consolidation of memories for past events, its role for prospective memory is still not well understood. Here, we show that sleep as compared to wakefulness after prospective memory instruction enhanced the successful execution of prospective memories two days later. We further show that sleep benefited both components of prospective memory, i.e. to remember that something has to be done (prospective component) and to remember what has to be done (retrospective component). Finally, sleep enhanced prospective remembering particularly when attentional resources were reduced during task execution, suggesting that subjects after sleep were able to recruit additional spontaneous-associative retrieval processes to remember intentions successfully. Our findings indicate that sleep supports the maintenance of prospective memory over time by strengthening intentional memory representations, thus favoring the spontaneous retrieval of the intended action at the appropriate time. PMID:24143246

Ca currents activated by spontaneous firing and synaptic disinhibition in neurons of the cerebellar nuclei

PubMed Central

Zheng, Nan; Raman, Indira M.

2009-01-01

In neurons of the cerebellar nuclei, long-term potentiation of EPSCs is induced by high-frequency synaptic excitation by mossy fibers followed by synaptic inhibition by Purkinje cells. Induction requires activation of synaptic receptors as well as voltage-gated Ca channels. To examine how Purkinje-mediated inhibition of nuclear neurons affects Ca levels during plasticity-inducing stimuli, we have combined electrophysiology, Ca imaging, and pharmacology of cerebellar nuclear neurons in mouse cerebellar slices. We find that spontaneous firing generates tonic Ca signals in both somata and dendrites, which drop during 500-ms, 100-Hz trains of Purkinje IPSPs or hyperpolarizing steps. Although the presence of low-voltage-activated (T-type) Ca channels in nuclear neurons has fostered the inference that disinhibition activates these channels, synaptic inhibition with a physiological ECl (−75 mV) fails to hyperpolarize neurons sufficiently for T-type channels to recover substantially. Consequently, after IPSPs, Ca signals return to baseline, although firing is accelerated by ∼20 Hz for ∼300 ms. Only after hyperpolarizations beyond ECl does Ca rise gradually beyond baseline, as firing further exceeds spontaneous rates. Cd2+ (100 μM), which nearly eliminates L-type, N-type, P/Q-type, and R-type Ca currents while sparing about half the T-type current, prevents Ca changes during and after hyperpolarizations to ECl. Thus, high-frequency IPSPs in cerebellar nuclear neurons evoke little post-inhibitory current through T-type channels. Instead, inhibition regulates Ca levels simply by preventing action potentials, which usually permit Ca influx through high-voltage-activated channels. The decreases and restoration of Ca levels associated with Purkinje-mediated inhibition are likely to contribute to synaptic plasticity. PMID:19657035

On the Origin of the 1,000 Hz Peak in the Spectrum of the Human Tympanic Electrical Noise

PubMed Central

Pardo-Jadue, Javiera; Dragicevic, Constantino D.; Bowen, Macarena; Delano, Paul H.

2017-01-01

The spectral analysis of the spontaneous activity recorded with an electrode positioned near the round window of the guinea pig cochlea shows a broad energy peak between 800 and 1,000 Hz. This spontaneous electric activity is called round window noise or ensemble background activity. In guinea pigs, the proposed origin of this peak is the random sum of the extracellular field potentials generated by action potentials of auditory nerve neurons. In this study, we used a non-invasive method to record the tympanic electric noise (TEN) in humans by means of a tympanic wick electrode. We recorded a total of 24 volunteers, under silent conditions or in response to stimuli of different modalities, including auditory, vestibular, and motor activity. Our results show a reliable peak of spontaneous activity at ~1,000 Hz in all studied subjects. In addition, we found stimulus-driven responses with broad-band noise that in most subjects produced an increase in the magnitude of the energy band around 1,000 Hz (between 650 and 1,200 Hz). Our results with the vestibular stimulation were not conclusive, as we found responses with all caloric stimuli, including 37°C. No responses were observed with motor tasks, like eye movements or blinking. We demonstrate the feasibility of recording neural activity from the electric noise of the tympanic membrane with a non-invasive method. From our results, we suggest that the 1,000 Hz component of the TEN has a mixed origin including peripheral and central auditory pathways. This research opens up the possibility of future clinical non-invasive techniques for the functional study of auditory and vestibular nerves in humans. PMID:28744193

Depolarized inactivation overcomes impaired activation to produce DRG neuron hyperexcitability in a Nav1.7 mutation in a patient with distal limb pain.

PubMed

Huang, Jianying; Yang, Yang; Dib-Hajj, Sulayman D; van Es, Michael; Zhao, Peng; Salomon, Jody; Drenth, Joost P H; Waxman, Stephen G

2014-09-10

Sodium channel Nav1.7, encoded by SCN9A, is expressed in DRG neurons and regulates their excitability. Genetic and functional studies have established a critical contribution of Nav1.7 to human pain disorders. We have now characterized a novel Nav1.7 mutation (R1279P) from a female human subject with distal limb pain, in which depolarized fast inactivation overrides impaired activation to produce hyperexcitability and spontaneous firing in DRG neurons. Whole-cell voltage-clamp recordings in human embryonic kidney (HEK) 293 cells demonstrated that R1279P significantly depolarizes steady-state fast-, slow-, and closed-state inactivation. It accelerates deactivation, decelerates inactivation, and facilitates repriming. The mutation increases ramp currents in response to slow depolarizations. Our voltage-clamp analysis showed that R1279P depolarizes channel activation, a change that was supported by our multistate structural modeling. Because this mutation confers both gain-of-function and loss-of-function attributes on the Nav1.7 channel, we tested the impact of R1279P expression on DRG neuron excitability. Current-clamp studies reveal that R1279P depolarizes resting membrane potential, decreases current threshold, and increases firing frequency of evoked action potentials within small DRG neurons. The populations of spontaneously firing and repetitively firing neurons were increased by expressing R1279P. These observations indicate that the dominant proexcitatory gating changes associated with this mutation, including depolarized steady-state fast-, slow-, and closed-state inactivation, faster repriming, and larger ramp currents, override the depolarizing shift of activation, to produce hyperexcitability and spontaneous firing of nociceptive neurons that underlie pain. Copyright © 2014 the authors 0270-6474/14/3412328-13$15.00/0.

On the Origin of the 1,000 Hz Peak in the Spectrum of the Human Tympanic Electrical Noise.

PubMed

Pardo-Jadue, Javiera; Dragicevic, Constantino D; Bowen, Macarena; Delano, Paul H

2017-01-01

The spectral analysis of the spontaneous activity recorded with an electrode positioned near the round window of the guinea pig cochlea shows a broad energy peak between 800 and 1,000 Hz. This spontaneous electric activity is called round window noise or ensemble background activity. In guinea pigs, the proposed origin of this peak is the random sum of the extracellular field potentials generated by action potentials of auditory nerve neurons. In this study, we used a non-invasive method to record the tympanic electric noise (TEN) in humans by means of a tympanic wick electrode. We recorded a total of 24 volunteers, under silent conditions or in response to stimuli of different modalities, including auditory, vestibular, and motor activity. Our results show a reliable peak of spontaneous activity at ~1,000 Hz in all studied subjects. In addition, we found stimulus-driven responses with broad-band noise that in most subjects produced an increase in the magnitude of the energy band around 1,000 Hz (between 650 and 1,200 Hz). Our results with the vestibular stimulation were not conclusive, as we found responses with all caloric stimuli, including 37°C. No responses were observed with motor tasks, like eye movements or blinking. We demonstrate the feasibility of recording neural activity from the electric noise of the tympanic membrane with a non-invasive method. From our results, we suggest that the 1,000 Hz component of the TEN has a mixed origin including peripheral and central auditory pathways. This research opens up the possibility of future clinical non-invasive techniques for the functional study of auditory and vestibular nerves in humans.

Assessment of the Tumorigenic Potential of Spontaneously Immortalized and hTERT-Immortalized Cultured Dental Pulp Stem Cells.

PubMed

Wilson, Ryan; Urraca, Nora; Skobowiat, Cezary; Hope, Kevin A; Miravalle, Leticia; Chamberlin, Reed; Donaldson, Martin; Seagroves, Tiffany N; Reiter, Lawrence T

2015-08-01

Dental pulp stem cells (DPSCs) provide an exciting new avenue to study neurogenetic disorders. DPSCs are neural crest-derived cells with the ability to differentiate into numerous tissues including neurons. The therapeutic potential of stem cell-derived lines exposed to culturing ex vivo before reintroduction into patients could be limited if the cultured cells acquired tumorigenic potential. We tested whether DPSCs that spontaneously immortalized in culture acquired features of transformed cells. We analyzed immortalized DPSCs for anchorage-independent growth, genomic instability, and ability to differentiate into neurons. Finally, we tested both spontaneously immortalized and human telomerase reverse transcriptase (hTERT)-immortalized DPSC lines for the ability to form tumors in immunocompromised animals. Although we observed increased colony-forming potential in soft agar for the spontaneously immortalized and hTERT-immortalized DPSC lines relative to low-passage DPSC, no tumors were detected from any of the DPSC lines tested. We noticed some genomic instability in hTERT-immortalized DPSCs but not in the spontaneously immortalized lines tested. We determined that immortalized DPSC lines generated in our laboratory, whether spontaneously or induced, have not acquired the potential to form tumors in mice. These data suggest cultured DPSC lines that can be differentiated into neurons may be safe for future in vivo therapy for neurobiological diseases. ©AlphaMed Press.

Dorsomedial prefontal cortex supports spontaneous thinking per se.

PubMed

Raij, T T; Riekki, T J J

2017-06-01

Spontaneous thinking, an action to produce, consider, integrate, and reason through mental representations, is central to our daily experience and has been suggested to serve crucial adaptive purposes. Such thinking occurs among other experiences during mind wandering that is associated with activation of the default mode network among other brain circuitries. Whether and how such brain activation is linked to the experience of spontaneous thinking per se remains poorly known. We studied 51 healthy subjects using a comprehensive experience-sampling paradigm during 3T functional magnetic resonance imaging. In comparison with fixation, the experiences of spontaneous thinking and spontaneous perception were related to activation of wide-spread brain circuitries, including the cortical midline structures, the anterior cingulate cortex and the visual cortex. In direct comparison of the spontaneous thinking versus spontaneous perception, activation was observed in the anterior dorsomedial prefrontal cortex. Modality congruence of spontaneous-experience-related brain activation was suggested by several findings, including association of the lingual gyrus with visual in comparison with non-verbal-non-visual thinking. In the context of current literature, these findings suggest that the cortical midline structures are involved in the integrative core substrate of spontaneous thinking that is coupled with other brain systems depending on the characteristics of thinking. Furthermore, involvement of the anterior dorsomedial prefrontal cortex suggests the control of high-order abstract functions to characterize spontaneous thinking per se. Hum Brain Mapp 38:3277-3288, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Conjecture about the 2-Flavour QCD Phase Diagram

NASA Astrophysics Data System (ADS)

Nava Blanco, M. A.; Bietenholz, W.; Fernández Téllez, A.

2017-10-01

The QCD phase diagram, in particular its sector of high baryon density, is one of the most prominent outstanding mysteries within the Standard Model of particle physics. We sketch a project how to arrive at a conjecture for the case of two massless quark flavours. The pattern of spontaneous chiral symmetry breaking is isomorphic to the spontaneous magnetisation in an O(4) non-linear σ-model, which can be employed as a low-energy effective theory to study the critical behaviour. We focus on the 3d O(4) model, where the configurations are divided into topological sectors, as in QCD. A topological winding with minimal Euclidean action is denoted as a skyrmion, and the topological charge corresponds to the QCD baryon number. This effective model can be simulated on a lattice with a powerful cluster algorithm, which should allow us to identify the features of the critical temperature, as we proceed from low to high baryon density. In this sense, this projected numerical study has the potential to provide us with a conjecture about the phase diagram of QCD with two massless quark flavours.

Chronic valproic acid treatment triggers increased neuropeptide y expression and signaling in rat nucleus reticularis thalami.

PubMed

Brill, Julia; Lee, Michelle; Zhao, Sheng; Fernald, Russell D; Huguenard, John R

2006-06-21

Valproate (VPA) can suppress absence and other seizures, but its precise mechanisms of action are not completely understood. We investigated whether VPA influences the expression of neuropeptide Y (NPY), an endogenous anticonvulsant. Chronic VPA administration to young rats (300-600 mg.kg(-1).d(-1) in divided doses over 4 d) resulted in a 30-50% increase in NPY mRNA and protein expression in the nucleus reticularis thalami (nRt) and hippocampus, but not in the neocortex, as shown by real-time PCR, radioimmunoassay, and immunohistochemistry. No increased expression was observed after a single acute dose of VPA. Chronic treatment with the pharmacologically inactive VPA analog octanoic acid did not elicit changes in NPY expression. No significant expression changes could be shown for the mRNAs of the Y1 receptor or of the neuropeptides somatostatin, vasoactive intestinal polypeptide, and choleocystokinin. Fewer synchronous spontaneous epileptiform oscillations were recorded in thalamic slices from VPA-treated animals, and oscillation duration as well as the period of spontaneous and evoked oscillations were decreased. Application of the Y1 receptor inhibitor N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginine-amide (BIBP3226) enhanced thalamic oscillations, indicating that NPY is released during those oscillations and acts to downregulate oscillatory strength. Chronic VPA treatment significantly potentiated the effect of BIBP3226 on oscillation duration but not on oscillation period. These results demonstrate a novel mechanism for the antiepileptic actions of chronic VPA therapy.

Selective functional interactions between excitatory and inhibitory cortical neurons and differential contribution to persistent activity of the slow oscillation.

PubMed

Tahvildari, Babak; Wölfel, Markus; Duque, Alvaro; McCormick, David A

2012-08-29

The neocortex depends upon a relative balance of recurrent excitation and inhibition for its operation. During spontaneous Up states, cortical pyramidal cells receive proportional barrages of excitatory and inhibitory synaptic potentials. Many of these synaptic potentials arise from the activity of nearby neurons, although the identity of these cells is relatively unknown, especially for those underlying the generation of inhibitory synaptic events. To address these fundamental questions, we developed an in vitro submerged slice preparation of the mouse entorhinal cortex that generates robust and regular spontaneous recurrent network activity in the form of the slow oscillation. By performing whole-cell recordings from multiple cell types identified with green fluorescent protein expression and electrophysiological and/or morphological properties, we show that distinct functional subpopulations of neurons exist in the entorhinal cortex, with large variations in contribution to the generation of balanced excitation and inhibition during the slow oscillation. The most active neurons during the slow oscillation are excitatory pyramidal and inhibitory fast spiking interneurons, receiving robust barrages of both excitatory and inhibitory synaptic potentials. Weak action potential activity was observed in stellate excitatory neurons and somatostatin-containing interneurons. In contrast, interneurons containing neuropeptide Y, vasoactive intestinal peptide, or the 5-hydroxytryptamine (serotonin) 3a receptor, were silent. Our data demonstrate remarkable functional specificity in the interactions between different excitatory and inhibitory cortical neuronal subtypes, and suggest that it is the large recurrent interaction between pyramidal neurons and fast spiking interneurons that is responsible for the generation of persistent activity that characterizes the depolarized states of the cortex.

Transcranial magnetic stimulation and potential cortical and trigeminothalamic mechanisms in migraine.

PubMed

Andreou, Anna P; Holland, Philip R; Akerman, Simon; Summ, Oliver; Fredrick, Joe; Goadsby, Peter J

2016-07-01

A single pulse of transcranial magnetic stimulation has been shown to be effective for the acute treatment of migraine with and without aura. Here we aimed to investigate the potential mechanisms of action of transcranial magnetic stimulation, using a transcortical approach, in preclinical migraine models. We tested the susceptibility of cortical spreading depression, the experimental correlate of migraine aura, and further evaluated the response of spontaneous and evoked trigeminovascular activity of second order trigemontothalamic and third order thalamocortical neurons in rats. Single pulse transcranial magnetic stimulation significantly inhibited both mechanical and chemically-induced cortical spreading depression when administered immediately post-induction in rats, but not when administered preinduction, and when controlled by a sham stimulation. Additionally transcranial magnetic stimulation significantly inhibited the spontaneous and evoked firing rate of third order thalamocortical projection neurons, but not second order neurons in the trigeminocervical complex, suggesting a potential modulatory effect that may underlie its utility in migraine. In gyrencephalic cat cortices, when administered post-cortical spreading depression, transcranial magnetic stimulation blocked the propagation of cortical spreading depression in two of eight animals. These results are the first to demonstrate that cortical spreading depression can be blocked in vivo using single pulse transcranial magnetic stimulation and further highlight a novel thalamocortical modulatory capacity that may explain the efficacy of magnetic stimulation in the treatment of migraine with and without aura. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Reconstruction of Cell Surface Densities of Ion Pumps, Exchangers, and Channels from mRNA Expression, Conductance Kinetics, Whole-Cell Calcium, and Current-Clamp Voltage Recordings, with an Application to Human Uterine Smooth Muscle Cells

PubMed Central

Atia, Jolene; McCloskey, Conor; Shmygol, Anatoly S.; Rand, David A.; van den Berg, Hugo A.; Blanks, Andrew M.

2016-01-01

Uterine smooth muscle cells remain quiescent throughout most of gestation, only generating spontaneous action potentials immediately prior to, and during, labor. This study presents a method that combines transcriptomics with biophysical recordings to characterise the conductance repertoire of these cells, the ‘conductance repertoire’ being the total complement of ion channels and transporters expressed by an electrically active cell. Transcriptomic analysis provides a set of potential electrogenic entities, of which the conductance repertoire is a subset. Each entity within the conductance repertoire was modeled independently and its gating parameter values were fixed using the available biophysical data. The only remaining free parameters were the surface densities for each entity. We characterise the space of combinations of surface densities (density vectors) consistent with experimentally observed membrane potential and calcium waveforms. This yields insights on the functional redundancy of the system as well as its behavioral versatility. Our approach couples high-throughput transcriptomic data with physiological behaviors in health and disease, and provides a formal method to link genotype to phenotype in excitable systems. We accurately predict current densities and chart functional redundancy. For example, we find that to evoke the observed voltage waveform, the BK channel is functionally redundant whereas hERG is essential. Furthermore, our analysis suggests that activation of calcium-activated chloride conductances by intracellular calcium release is the key factor underlying spontaneous depolarisations. PMID:27105427

Fluctuations in Mass-Action Equilibrium of Protein Binding Networks

NASA Astrophysics Data System (ADS)

Yan, Koon-Kiu; Walker, Dylan; Maslov, Sergei

2008-12-01

We consider two types of fluctuations in the mass-action equilibrium in protein binding networks. The first type is driven by slow changes in total concentrations of interacting proteins. The second type (spontaneous) is caused by quickly decaying thermodynamic deviations away from equilibrium. We investigate the effects of network connectivity on fluctuations by comparing them to scenarios in which the interacting pair is isolated from the network and analytically derives bounds on fluctuations. Collective effects are shown to sometimes lead to large amplification of spontaneous fluctuations. The strength of both types of fluctuations is positively correlated with the complex connectivity and negatively correlated with complex concentration. Our general findings are illustrated using a curated network of protein interactions and multiprotein complexes in baker’s yeast, with empirical protein concentrations.

Spontaneous in-flight accommodation of hand orientation to unseen grasp targets: A case of action blindsight.

PubMed

Prentiss, Emily K; Schneider, Colleen L; Williams, Zoë R; Sahin, Bogachan; Mahon, Bradford Z

2018-03-15

The division of labour between the dorsal and ventral visual pathways is well established. The ventral stream supports object identification, while the dorsal stream supports online processing of visual information in the service of visually guided actions. Here, we report a case of an individual with a right inferior quadrantanopia who exhibited accurate spontaneous rotation of his wrist when grasping a target object in his blind visual field. His accurate wrist orientation was observed despite the fact that he exhibited no sensitivity to the orientation of the handle in a perceptual matching task. These findings indicate that non-geniculostriate visual pathways process basic volumetric information relevant to grasping, and reinforce the observation that phenomenal awareness is not necessary for an object's volumetric properties to influence visuomotor performance.

Counterfactual Thinking Deficit in Huntington's Disease.

PubMed

Solca, Federica; Poletti, Barbara; Zago, Stefano; Crespi, Chiara; Sassone, Francesca; Lafronza, Annalisa; Maraschi, Anna Maria; Sassone, Jenny; Silani, Vincenzo; Ciammola, Andrea

2015-01-01

Counterfactual thinking (CFT) refers to the generation of mental simulations of alternatives to past events, actions and outcomes. CFT is a pervasive cognitive feature in every-day life and is closely related to decision-making, planning and problem-solving - all of which are cognitive processes linked to unimpaired frontal lobe functioning. Huntington's Disease (HD) is a neurodegenerative disorder characterised by motor, behavioral and cognitive dysfunctions. Because an impairment in frontal and executive functions has been described in HD, we hypothesised that HD patients may have a CFT impairment. Tests of spontaneous counterfactual thoughts and counterfactual-derived inferences were administered to 24 symptomatic HD patients and 24 age- and sex-matched healthy subjects. Our results show a significant impairment in the spontaneous generation of CFT and low performance on the Counterfactual Inference Test (CIT) in HD patients. Low performance on the spontaneous CFT test significantly correlates with impaired attention abilities, verbal fluency and frontal lobe efficiency, as measured by Trail Making Test - Part A, Phonemic Verbal Fluency Test and FAB. Spontaneous CFT and the use of this type of reasoning are impaired in HD patients. This deficit may be related to frontal lobe dysfunction, which is a hallmark of HD. Because CFT has a pervasive role in patients' daily lives regarding their planning, decision making and problem solving skills, cognitive rehabilitation may improve HD patients' ability to analyse current behaviors and future actions.

Genetic dissection of ion currents underlying all-or-none action potentials in C. elegans body-wall muscle cells

PubMed Central

Liu, Ping; Ge, Qian; Chen, Bojun; Salkoff, Lawrence; Kotlikoff, Michael I; Wang, Zhao-Wen

2011-01-01

Although the neuromuscular system of C. elegans has been studied intensively, little is known about the properties of muscle action potentials (APs). By combining mutant analyses with in vivo electrophysiological recording techniques and Ca2+ imaging, we have established the fundamental properties and molecular determinants of body-wall muscle APs. We show that, unlike mammalian skeletal muscle APs, C. elegans muscle APs occur in spontaneous trains, do not require the function of postsynaptic receptors, and are all-or-none overshooting events, rather than graded potentials as has been previously reported. Furthermore, we show that muscle APs depend on Ca2+ entry through the L-type Ca2+ channel EGL-19 with a contribution from the T-type Ca2+ channel CCA-1. Both the Shaker K+ channel SHK-1 and the Ca2+/Cl−-gated K+ channel SLO-2 play important roles in controlling the speed of membrane repolarization, the amplitude of afterhyperpolarization (AHP) and the pattern of AP firing; SLO-2 is also important in setting the resting membrane potential. Finally, AP-elicited elevations of [Ca2+]i require both EGL-19 and the ryanodine receptor UNC-68. Thus, like mammalian skeletal muscle, C. elegans body-wall myocytes generate all-or-none APs, which evoke Ca2+ release from the sarcoplasmic reticulum (SR), although the specific ion channels used for AP upstroke and repolarization differ. PMID:21059759

Effect of 1.8 GHz radiofrequency electromagnetic radiation on novel object associative recognition memory in mice

PubMed Central

Wang, Kai; Lu, Jun-Mei; Xing, Zhen-He; Zhao, Qian-Ru; Hu, Lin-Qi; Xue, Lei; Zhang, Jie; Mei, Yan-Ai

2017-01-01

Mounting evidence suggests that exposure to radiofrequency electromagnetic radiation (RF-EMR) can influence learning and memory in rodents. In this study, we examined the effects of single exposure to 1.8 GHz RF-EMR for 30 min on subsequent recognition memory in mice, using the novel object recognition task (NORT). RF-EMR exposure at an intensity of >2.2 W/kg specific absorption rate (SAR) power density induced a significant density-dependent increase in NORT index with no corresponding changes in spontaneous locomotor activity. RF-EMR exposure increased dendritic-spine density and length in hippocampal and prefrontal cortical neurons, as shown by Golgi staining. Whole-cell recordings in acute hippocampal and medial prefrontal cortical slices showed that RF-EMR exposure significantly altered the resting membrane potential and action potential frequency, and reduced the action potential half-width, threshold, and onset delay in pyramidal neurons. These results demonstrate that exposure to 1.8 GHz RF-EMR for 30 min can significantly increase recognition memory in mice, and can change dendritic-spine morphology and neuronal excitability in the hippocampus and prefrontal cortex. The SAR in this study (3.3 W/kg) was outside the range encountered in normal daily life, and its relevance as a potential therapeutic approach for disorders associated with recognition memory deficits remains to be clarified. PMID:28303965

Spontaneous Action Representation in Smokers when Watching Movie Characters Smoke

PubMed Central

Wagner, Dylan D.; Cin, Sonya Dal; Sargent, James D.; Kelley, William M.; Heatherton, Todd F.

2013-01-01

Do smokers simulate smoking when they see someone else smoke? For regular smokers, smoking is such a highly practiced motor skill that it often occurs automatically, without conscious awareness. Research on the brain basis of action observation has delineated a frontopareital network that is commonly recruited when people observe, plan or imitate actions. Here, we investigated whether this action observation network would be preferentially recruited in smokers when viewing complex smoking cues, such as those occurring in motion pictures. Seventeen right-handed smokers and seventeen non-smokers watched a popular movie while undergoing functional magnetic resonance imaging. Using a natural stimulus, such as a movie, allowd us to keep both smoking and non-smoking participants naïve to the goals of the experiment. Brain activity evoked by scenes of movie smoking was contrasted with non-smoking control scenes which were matched for frequency and duration. Compared to non-smokers, smokers showed greater activity in left anterior intraparietal sulcus and inferior frontal gyrus, both regions involved in the simulation of contralateral hand-based gestures, when viewing smoking vs. control scenes. These results demonstrate that smokers spontaneously represent the action of smoking when viewing others smoke, the consequence of which may make it more difficult to abstain from smoking. PMID:21248113

A geophysical system combining electrical resistivity and spontaneous potential for detecting, delineating, and monitoring slope stability.

DOT National Transportation Integrated Search

1991-01-01

Various geophysical electrical measuring techniques, i.e., spontaneous potential (SP) terrain conductivity meter (TCM), and conventional electrical resistivity/conductivity (ER), were tested to determine their effectiveness in detecting, delineating,...

Perioperative spontaneous bilateral suprachoroidal hemorrhage

PubMed Central

Haridas, Anjana; Litwin, Andre S.; Coker, Timothy

2011-01-01

Summary Suprachoroidal hemorrhage is a rare condition, occurring most commonly in the perioperative period, although cases of unilateral spontaneous hemorrhages have been reported. We report a case of bilateral spontaneous suprachoroidal hemorrhage and discuss the potential causative factors. PMID:23362387

Modulation of synaptic transmission from segmental afferents by spontaneous activity of dorsal horn spinal neurones in the cat.

PubMed

Manjarrez, E; Rojas-Piloni, J G; Jimenez, I; Rudomin, P

2000-12-01

We examined, in the anaesthetised cat, the influence of the neuronal ensembles producing spontaneous negative cord dorsum potentials (nCDPs) on segmental pathways mediating primary afferent depolarisation (PAD) of cutaneous and group I muscle afferents and on Ia monosynaptic activation of spinal motoneurones. The intraspinal distribution of the field potentials associated with the spontaneous nCDPs indicated that the neuronal ensembles involved in the generation of these potentials were located in the dorsal horn of lumbar segments, in the same region of termination of low-threshold cutaneous afferents. During the occurrence of spontaneous nCDPs, transmission from low-threshold cutaneous afferents to second order neurones in laminae III-VI, as well as transmission along pathways mediating PAD of cutaneous and Ib afferents, was facilitated. PAD of Ia afferents was instead inhibited. Monosynaptic reflexes of flexors and extensors were facilitated during the spontaneous nCDPs. The magnitude of the facilitation was proportional to the amplitude of the 'conditioning' spontaneous nCDPs. This led to a high positive correlation between amplitude fluctuations of spontaneous nCDPs and fluctuations of monosynaptic reflexes. Stimulation of low-threshold cutaneous afferents transiently reduced the probability of occurrence of spontaneous nCDPs as well as the fluctuations of monosynaptic reflexes. It is concluded that the spontaneous nCDPs were produced by the activation of a population of dorsal horn neurones that shared the same functional pathways and involved the same set of neurones as those responding monosynaptically to stimulation of large cutaneous afferents. The spontaneous activity of these neurones was probably the main cause of the fluctuations of the monosynaptic reflexes observed under anaesthesia and could provide a dynamic linkage between segmental sensory and motor pathways.

Computational modeling of inhibition of voltage-gated Ca channels: identification of different effects on uterine and cardiac action potentials.

PubMed

Tong, Wing-Chiu; Ghouri, Iffath; Taggart, Michael J

2014-01-01

The uterus and heart share the important physiological feature whereby contractile activation of the muscle tissue is regulated by the generation of periodic, spontaneous electrical action potentials (APs). Preterm birth arising from premature uterine contractions is a major complication of pregnancy and there remains a need to pursue avenues of research that facilitate the use of drugs, tocolytics, to limit these inappropriate contractions without deleterious actions on cardiac electrical excitation. A novel approach is to make use of mathematical models of uterine and cardiac APs, which incorporate many ionic currents contributing to the AP forms, and test the cell-specific responses to interventions. We have used three such models-of uterine smooth muscle cells (USMC), cardiac sinoatrial node cells (SAN), and ventricular cells-to investigate the relative effects of reducing two important voltage-gated Ca currents-the L-type (ICaL) and T-type (ICaT) Ca currents. Reduction of ICaL (10%) alone, or ICaT (40%) alone, blunted USMC APs with little effect on ventricular APs and only mild effects on SAN activity. Larger reductions in either current further attenuated the USMC APs but with also greater effects on SAN APs. Encouragingly, a combination of ICaL and ICaT reduction did blunt USMC APs as intended with little detriment to APs of either cardiac cell type. Subsequent overlapping maps of ICaL and ICaT inhibition profiles from each model revealed a range of combined reductions of ICaL and ICaT over which an appreciable diminution of USMC APs could be achieved with no deleterious action on cardiac SAN or ventricular APs. This novel approach illustrates the potential for computational biology to inform us of possible uterine and cardiac cell-specific mechanisms. Incorporating such computational approaches in future studies directed at designing new, or repurposing existing, tocolytics will be beneficial for establishing a desired uterine specificity of action.

Computational modeling of inhibition of voltage-gated Ca channels: identification of different effects on uterine and cardiac action potentials

PubMed Central

Tong, Wing-Chiu; Ghouri, Iffath; Taggart, Michael J.

2014-01-01

The uterus and heart share the important physiological feature whereby contractile activation of the muscle tissue is regulated by the generation of periodic, spontaneous electrical action potentials (APs). Preterm birth arising from premature uterine contractions is a major complication of pregnancy and there remains a need to pursue avenues of research that facilitate the use of drugs, tocolytics, to limit these inappropriate contractions without deleterious actions on cardiac electrical excitation. A novel approach is to make use of mathematical models of uterine and cardiac APs, which incorporate many ionic currents contributing to the AP forms, and test the cell-specific responses to interventions. We have used three such models—of uterine smooth muscle cells (USMC), cardiac sinoatrial node cells (SAN), and ventricular cells—to investigate the relative effects of reducing two important voltage-gated Ca currents—the L-type (ICaL) and T-type (ICaT) Ca currents. Reduction of ICaL (10%) alone, or ICaT (40%) alone, blunted USMC APs with little effect on ventricular APs and only mild effects on SAN activity. Larger reductions in either current further attenuated the USMC APs but with also greater effects on SAN APs. Encouragingly, a combination of ICaL and ICaT reduction did blunt USMC APs as intended with little detriment to APs of either cardiac cell type. Subsequent overlapping maps of ICaL and ICaT inhibition profiles from each model revealed a range of combined reductions of ICaL and ICaT over which an appreciable diminution of USMC APs could be achieved with no deleterious action on cardiac SAN or ventricular APs. This novel approach illustrates the potential for computational biology to inform us of possible uterine and cardiac cell-specific mechanisms. Incorporating such computational approaches in future studies directed at designing new, or repurposing existing, tocolytics will be beneficial for establishing a desired uterine specificity of action. PMID:25360118

Effects of imatinib mesylate on spontaneous electrical and mechanical activity in smooth muscle of the guinea-pig stomach

PubMed Central

Hashitani, H; Hayase, M; Suzuki, H

2008-01-01

Background and purpose: Effects of imatinib mesylate, a Kit receptor tyrosine kinase inhibitor, on spontaneous activity of interstitial cells of Cajal (ICC) and smooth muscles in the stomach were investigated. Experimental approach: Effects of imatinib on spontaneous electrical and mechanical activity were investigated by measuring changes in the membrane potential and tension recorded from smooth muscles of the guinea-pig stomach. Its effects on spontaneous changes in intracellular concentration of Ca2+ ([Ca2+]i) (Ca2+ transients) were also examined in fura-2-loaded preparations. Key results: Imatinib (1–10 μM) suppressed spontaneous contractions and Ca2+ transients. Simultaneous recordings of electrical and mechanical activity demonstrated that imatinib (1 μM) reduced the amplitude of spontaneous contractions without suppressing corresponding slow waves. In the presence of nifedipine (1 μM), imatinib (10 μM) reduced the duration of slow waves and follower potentials in the antrum and accelerated their generation, but had little affect on their amplitude. In contrast, imatinib reduced the amplitude of antral slow potentials and slow waves in the corpus. Conclusions and implications: Imatinib may suppress spontaneous contractions of gastric smooth muscles by inhibiting pathways that increase [Ca2+]i in smooth muscles rather than by specifically inhibiting the activity of ICC. A high concentration of imatinib (10 μM) reduced the duration of slow waves or follower potentials in the antrum, which reflect activity of ICC distributed in the myenteric layers (ICC-MY), and suppressed antral slow potentials or corporal slow waves, which reflect activity of ICC within the muscle bundles (ICC-IM), presumably by inhibiting intracellular Ca2+ handling. PMID:18414381

New insights into the acute actions from a high dosage of fluoxetine on neuronal and cardiac function: Drosophila, crayfish and rodent models.

PubMed

Majeed, Zana R; Ritter, Kyle; Robinson, Jonathan; Blümich, Sandra L E; Brailoiu, Eugen; Cooper, Robin L

2015-01-01

The commonly used mood altering drug fluoxetine (Prozac) in humans has a low occurrence in reports of harmful effects from overdose; however, individuals with altered metabolism of the drug and accidental overdose have led to critical conditions and even death. We addressed direct actions of high concentrations on synaptic transmission at neuromuscular junctions (NMJs), neural properties, and cardiac function unrelated to fluoxetine's action as a selective 5-HT reuptake inhibitor. There appears to be action in blocking action potentials in crayfish axons, enhanced occurrences of spontaneous synaptic vesicle fusion events in the presynaptic terminals at NMJs of both Drosophila and crayfish. In rodent neurons, cytoplasmic Ca(2+) rises by fluoxetine and is thapsigargin dependent. The Drosophila larval heart showed a dose dependent effect in cardiac arrest. Acute paralytic behavior in crayfish occurred at a systemic concentration of 2mM. A high percentage of death as well as slowed development occurred in Drosophila larvae consuming food containing 100μM fluoxetine. The release of Ca(2+) from the endoplasmic reticulum in neurons and the cardiac tissue as well as blockage of voltage-gated Na(+) channels in neurons could explain the effects on the whole animal as well as the isolated tissues. The use of various animal models in demonstrating the potential mechanisms for the toxic effects with high doses of fluoxetine maybe beneficial for acute treatments in humans. Future studies in determining how fluoxetine is internalized in cells and if there are subtle effects of these mentioned mechanisms presented with chronic therapeutic doses are of general interest. Copyright © 2015 Elsevier Inc. All rights reserved.

Visual Experience Enhances Infants' Use of Task-Relevant Information in an Action Task

ERIC Educational Resources Information Center

Wang, Su-hua; Kohne, Lisa

2007-01-01

Four experiments examined whether infants' use of task-relevant information in an action task could be facilitated by visual experience in the laboratory. Twelve- but not 9-month-old infants spontaneously used height information and chose an appropriate (taller) cover in search of a hidden tall toy. After watching examples of covering events in a…

The aesthetic rationality of the popular expressive arts: Lifeworld communication among breast cancer survivors living with lymphedema

PubMed Central

Quinlan, Elizabeth; Thomas, Roanne; Ahmed, Shahid; Fichtner, Pam; McMullen, Linda; Block, Janice

2014-01-01

The use of popular expressive arts as antidotes to the pathologies of the parallel processes of lifeworld colonization and cultural impoverishment has been under-theorized. This article enters the void with a project in which breast cancer survivors used collages and installations of everyday objects to solicit their authentic expression of the psycho-social impacts of lymphedema. The article enlists Jurgen Habermas' communicative action theory to explore the potential of these expressive arts to expand participants' meaningful engagement with their lifeworlds. The findings point to the unique non-linguistic discursivity of these non-institutional artistic forms as their liberating power to disclose silenced human needs: the images ‘spoke' for themselves for group members to recognize shared subjectivities. The authenticity claims inherent in the art forms fostered collective reflexivity and spontaneous, affective responses and compelled the group to create new collective understandings of the experience of living with lymphedema. The article contributes theoretical insights regarding the emancipatory potential of aesthetic-expressive rationality, an under-developed area of Habermasian theory of communicative action, and to the burgeoning literature on arts-based methods in social scientific research. PMID:25197263

Reduced intrinsic heart rate is associated with reduced arrhythmic susceptibility in guinea-pig heart.

PubMed

Osadchii, Oleg E

2014-12-01

In the clinical setting, patients with slower resting heart rate are less prone to cardiovascular death compared with those with elevated heart rate. However, electrophysiological adaptations associated with reduced cardiac rhythm have not been thoroughly explored. In this study, relationships between intrinsic heart rate and arrhythmic susceptibility were examined by assessments of action potential duration (APD) rate adaptation and inducibility of repolarization alternans in sinoatrial node (SAN)-driven and atrioventricular (AV)-blocked guinea-pig hearts perfused with Langendorff apparatus. Electrocardiograms, epicardial monophasic action potentials, and effective refractory periods (ERP) were assessed in normokalemic and hypokalemic conditions. Slower basal heart rate in AV-blocked hearts was associated with prolonged ventricular repolarization during spontaneous beating, and with attenuated APD shortening at increased cardiac activation rates during dynamic pacing, when compared with SAN-driven hearts. During hypokalemic perfusion, the inducibility of repolarization alternans and tachyarrhythmia by rapid pacing was found to be lower in AV-blocked hearts. This difference was ascribed to prolonged ERP in the setting of reduced basal heart rate, which prevented ventricular capture at critically short pacing intervals required to induce arrhythmia. Reduced basal heart rate is associated with electrophysiological changes that prevent electrical instability upon an abrupt cardiac acceleration.

The aesthetic rationality of the popular expressive arts: Lifeworld communication among breast cancer survivors living with lymphedema.

PubMed

Quinlan, Elizabeth; Thomas, Roanne; Ahmed, Shahid; Fichtner, Pam; McMullen, Linda; Block, Janice

2014-08-01

The use of popular expressive arts as antidotes to the pathologies of the parallel processes of lifeworld colonization and cultural impoverishment has been under-theorized. This article enters the void with a project in which breast cancer survivors used collages and installations of everyday objects to solicit their authentic expression of the psycho-social impacts of lymphedema. The article enlists Jurgen Habermas' communicative action theory to explore the potential of these expressive arts to expand participants' meaningful engagement with their lifeworlds. The findings point to the unique non-linguistic discursivity of these non-institutional artistic forms as their liberating power to disclose silenced human needs: the images 'spoke' for themselves for group members to recognize shared subjectivities. The authenticity claims inherent in the art forms fostered collective reflexivity and spontaneous, affective responses and compelled the group to create new collective understandings of the experience of living with lymphedema. The article contributes theoretical insights regarding the emancipatory potential of aesthetic-expressive rationality, an under-developed area of Habermasian theory of communicative action, and to the burgeoning literature on arts-based methods in social scientific research.

Catecholamine exocytosis during low frequency stimulation in mouse adrenal chromaffin cells is primarily asynchronous and controlled by the novel mechanism of Ca2+ syntilla suppression

PubMed Central

Lefkowitz, Jason J; DeCrescenzo, Valerie; Duan, Kailai; Bellve, Karl D; Fogarty, Kevin E; Walsh, John V; ZhuGe, Ronghua

2014-01-01

Adrenal chromaffin cells (ACCs), stimulated by the splanchnic nerve, generate action potentials (APs) at a frequency near 0.5 Hz in the resting physiological state, at times described as ‘rest and digest’. How such low frequency stimulation in turn elicits sufficient catecholamine exocytosis to set basal sympathetic tone is not readily explained by the classical mechanism of stimulus–secretion coupling, where exocytosis is synchronized to AP-induced Ca2+ influx. By using simulated action potentials (sAPs) at 0.5 Hz in isolated patch-clamped mouse ACCs, we show here that less than 10% of all catecholaminergic exocytosis, measured by carbon fibre amperometry, is synchronized to an AP. The asynchronous phase, the dominant phase, of exocytosis does not require Ca2+ influx. Furthermore, increased asynchronous exocytosis is accompanied by an AP-dependent decrease in frequency of Ca2+ syntillas (i.e. transient, focal Ca2+ release from internal stores) and is ryanodine sensitive. We propose a mechanism of disinhibition, wherein APs suppress Ca2+ syntillas, which themselves inhibit exocytosis as they do in the case of spontaneous catecholaminergic exocytosis. PMID:25128575

Electrophysiological effects of FK664, a new cardiotonic agent, on preparations from guinea pig ventricle and from rabbit sino-atrial node.

PubMed

Kodama, I; Anno, T; Sudo, Y; Satake, N; Shibata, S

1989-05-01

Effects of the cardiotonic agent FK664, 6-(3, 4-dimethoxy-phenyl)-1-ethyl-4-mesitylimino-3-methyl-3,4-dihydro-2 (1H)-pyrimidone, on isolated guinea pig ventricular muscles and rabbit sinus node pacemaker cells were studied using micro-electrode techniques. In ventricular muscles driven at 0.5-1.0 Hz, FK664 above 3 mumol.litre-1 caused an increase in contractile force and a shortening of time to peak tension. This positive inotropic effect of FK664 was accompanied by a slight elevation of the early plateau phase of the action potential, while other action potential variables were unaffected. The change in contractile force induced by FK664 was abolished in a low Ca2+ medium (0.12 mmol.litre-1) or by treatment with ryanodine (2 mumol.litre-1), whereas it was relatively well preserved in the preparations pretreated with nefedipine (1 mumol.litre-1). The slow action potentials induced by isoprenaline (0.3 mumol.litre-1) in high K+ medium (30 mmol.litre-1) and the slow inward current measured by single sucrose gap voltage clamp at a holding potential of -40 mV were unaffected by FK664. In sinus node pacemaker cells, FK664 (1-10 mumol.litre-1) caused a dose dependent acceleration of phase 4 depolarisation and a shortening of spontaneous firing cycle length. This positive chronotropic effect of FK664 was markedly inhibited in a low Ca2+ medium (0.3 mmol.litre-1). These findings suggest that FK664 has positive inotropic and chronotropic effects on the heart, due to an enhancement of transsarcolemmal calcium influx through the low threshold, dihydropyridine insensitive Ca2+ channel population.

Developmental axon stretch stimulates neuron growth while maintaining normal electrical activity, intracellular calcium flux, and somatic morphology

PubMed Central

Loverde, Joseph R.; Pfister, Bryan J.

2015-01-01

Elongation of nerve fibers intuitively occurs throughout mammalian development, and is synchronized with expansion of the growing body. While most tissue systems enlarge through mitosis and differentiation, elongation of nerve fibers is remarkably unique. The emerging paradigm suggests that axons undergo stretch as contiguous tissues enlarge between the proximal and distal segments of spanning nerve fibers. While stretch is distinct from growth, tension is a known stimulus which regulates the growth of axons. Here, we hypothesized that the axon stretch-growth process may be a natural form of injury, whereby regenerative processes fortify elongating axons in order to prevent disconnection. Harnessing the live imaging capability of our axon stretch-growth bioreactors, we assessed neurons both during and following stretch for biomarkers associated with injury. Utilizing whole-cell patch clamp recording, we found no evidence of changes in spontaneous action potential activity or degradation of elicited action potentials during real-time axon stretch at strains of up to 18% applied over 5 min. Unlike traumatic axonal injury, functional calcium imaging of the soma revealed no shifts in free intracellular calcium during axon stretch. Finally, the cross-sectional areas of nuclei and cytoplasms were normal, with no evidence of chromatolysis following week-long stretch-growth limited to the lower of 25% strain or 3 mm total daily stretch. The neuronal growth cascade coupled to stretch was concluded to be independent of the changes in membrane potential, action potential generation, or calcium flux associated with traumatic injury. While axon stretch-growth is likely to share overlap with regenerative processes, we conclude that developmental stretch is a distinct stimulus from traumatic axon injury. PMID:26379492

Squids in the Study of Cerebral Magnetic Field

NASA Astrophysics Data System (ADS)

Romani, G. L.; Narici, L.

The following sections are included: * INTRODUCTION * HISTORICAL OVERVIEW * NEUROMAGNETIC FIELDS AND AMBIENT NOISE * DETECTORS * Room temperature sensors * SQUIDs * DETECTION COILS * Magnetometers * Gradiometers * Balancing * Planar gradiometers * Choice of the gradiometer parameters * MODELING * Current pattern due to neural excitations * Action potentials and postsynaptic currents * The current dipole model * Neural population and detected fields * Spherically bounded medium * SPATIAL CONFIGURATION OF THE SENSORS * SOURCE LOCALIZATION * Localization procedure * Experimental accuracy and reproducibility * SIGNAL PROCESSING * Analog Filtering * Bandpass filters * Line rejection filters * DATA ANALYSIS * Analysis of evoked/event-related responses * Simple average * Selected average * Recursive techniques * Similarity analysis * Analysis of spontaneous activity * Mapping and localization * EXAMPLES OF NEUROMAGNETIC STUDIES * Neuromagnetic measurements * Studies on the normal brain * Clinical applications * Epilepsy * Tinnitus * CONCLUSIONS * ACKNOWLEDGEMENTS * REFERENCES

Acute, Nontraumatic Spontaneous Spinal Subdural Hematoma: A Case Report and Systematic Review of the Literature

PubMed Central

Abel, Taylor J.

2017-01-01

Spontaneous spinal subdural hematoma (sSDH) is a rare condition outright. Moreover, cases that occur spontaneously in the absence of an identifiable etiology are considerably less common and remain poorly understood. Here, we present the case of a 43-year-old man with spontaneous sSDH presenting with acute onset low back pain and paraplegia. Urgent magnetic resonance imaging identified a dorsal SDH from T8 to T11 with compression of the spinal cord. Emergent T8–T10 laminectomies with intradural exploration and hematoma evacuation were performed. However, despite prompt identification and appropriate action, the patient's recovery was modest and significant disability remained at discharge. This unique and unusual case demonstrates that spontaneous sSDH requires prompt surgical treatment to minimize associated morbidity and supports the association between the presence of severe neurological deficits upon initial presentation with less favorable outcomes. We performed a comprehensive systematic review of spontaneous sSDH of unknown etiology, which demonstrates that emergent surgical intervention is indicated for patients presenting with severe neurological deficits and the presence of these deficits is predictive of poor neurological outcome. Furthermore, conservative management should be considered in patients presenting with mild neurological deficits as spontaneous resolution followed by favorable neurological outcomes is often observed in these patients. PMID:29441210

Making sense of early false-belief understanding.

PubMed

Helming, Katharina A; Strickland, Brent; Jacob, Pierre

2014-04-01

We address the puzzle about early belief ascription: young children fail elicited-response false-belief tasks, but they demonstrate spontaneous false-belief understanding. Based on recent converging evidence, we articulate a pragmatic framework to solve this puzzle. Young children do understand the contents of others' false belief, but they are overwhelmed when they must simultaneously make sense of two distinct actions: the instrumental action of a mistaken agent and the experimenter's communicative action. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Mechanism of action of neurotoxins acting on the inactivation of voltage-gated sodium channels].

PubMed

Benoit, E

1998-01-01

This review focuses on the mechanism(s) of action of neurotoxins acting on the inactivation of voltage-gated Na channels. Na channels are transmembrane proteins which are fundamental for cellular communication. These proteins form pores in the plasma membrane allowing passive ionic movements to occur. Their opening and closing are controlled by gating systems which depend on both membrane potential and time. Na channels have three functional properties, mainly studied using electrophysiological and biochemical techniques, to ensure their role in the generation and propagation of action potentials: 1) a highly selectivity for Na ions, 2) a rapid opening ("activation"), responsible for the depolarizing phase of the action potential, and 3) a late closing ("inactivation") involved in the repolarizing phase of the action potential. As an essential protein for membrane excitability, the Na channel is the specific target of a number of vegetal and animal toxins which, by binding to the channel, alter its activity by affecting one or more of its properties. At least six toxin receptor sites have been identified on the neuronal Na channel on the basis of binding studies. However, only toxins interacting with four of these sites (sites 2, 3, 5 et 6) produce alterations of channel inactivation. The maximal percentage of Na channels modified by the binding of neurotoxins to sites 2 (batrachotoxin and some alkaloids), 3 (alpha-scorpion and sea anemone toxins), 5 (brevetoxins and ciguatoxins) et 6 (delta-conotoxins) is different according to the site considered. However, in all cases, these channels do not inactivate. Moreover, Na channels modified by toxins which bind to sites 2, 5 and 6 activate at membrane potentials more negative than do unmodified channels. The physiological consequences of Na channel modifications, induced by the binding of neurotoxins to sites 2, 3, 5 and 6, are (i) an inhibition of cellular excitability due to an important membrane depolarization (site 2), (ii) a decrease of cellular excitability due to an important increase in the action potential duration (site 3) and (iii) an increase in cellular excitability which results in spontaneous and repetitive firing of action potentials (sites 5 and 6). The biochemical and electrophysiological studies performed with these toxins, as well as the determination of their molecular structure, have given basic information on the function and structure of the Na channel protein. Therefore, various models representing the different states of Na channels have been proposed to account for the neurotoxin-induced modifications of Na inactivation. Moreover, the localization of receptor binding sites 2, 3, 5 et 6 for these toxins on the neuronal Na channel has been deduced and the molecular identification of the recognition site(s) for some of them has been established on the alpha sub-unit forming the Na channel protein.

Clash of symmetries in a Randall-Sundrum-like spacetime

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dando, Gareth; George, Damien P.; Volkas, Raymond R.

2005-08-15

We present a toy model that exhibits clash-of-symmetries style Higgs field kink configurations in a Randall-Sundrum-like spacetime. The model has two complex scalar fields {phi}{sub 1,2}, with a sextic potential obeying global U(1)xU(1) and discrete {phi}{sub 1}{r_reversible}{phi}{sub 2} interchange symmetries. The scalar fields are coupled to 4+1 dimensional gravity endowed with a bulk cosmological constant. We show that the coupled Einstein-Higgs field equations have an interesting analytic solution provided the sextic potential adopts a particular form. The 4+1 metric is shown to be that of a smoothed-out Randall-Sundrum type of spacetime. The thin-brane Randall-Sundrum limit, whereby the Higgs field kinksmore » become step functions, is carefully defined in terms of the fundamental parameters in the action. The 'clash-of-symmetries' feature, defined in previous papers, is manifested here through the fact that both of the U(1) symmetries are spontaneously broken at all nonasymptotic points in the extra dimension w. One of the U(1)'s is asymptotically restored as w{yields}-{infinity}, with the other U(1) restored as w{yields}+{infinity}. The spontaneously broken discrete symmetry ensures topological stability. In the gauged version of this model we find new flat-space solutions, but in the warped metric case we have been unable to find any solutions with nonzero gauge fields.« less

Brain-derived neurotrophic factor blocks long-term depression in solitary neurones cultured from rat visual cortex

PubMed Central

Kumura, Eiji; Kimura, Fumitaka; Taniguchi, Nobuaki; Tsumoto, Tadaharu

2000-01-01

To address questions of whether long-term depression (LTD) in the visual cortex is expressed in pre- or postsynaptic sites, whether brain-derived neurotrophic factor (BDNF) exerts its LTD-blocking action without involvement of GABAergic inhibition, and whether the action of BDNF is pre- or postsynaptic, we observed excitatory postsynaptic currents (EPSCs) from solitary neurones cultured on glial microislands. In this preparation GABAergic inhibition is not involved and a group of synapses (autapses) which generate evoked EPSCs is thought to be the same as those generating spontaneous EPSCs. A short depolarising voltage step to the soma generated Na+ spikes which were followed by autaptic EPSCs. When this somatic activation was paired with prolonged depolarisation for 100 ms to −30 mV and repeated at 1 Hz for 5 min, LTD was induced in all of the nine cells tested. Then, the frequency of spontaneous EPSCs decreased, but the amplitude did not change, suggesting that the site of LTD expression is presynaptic. Application of BDNF at 50 ng ml−1 blocked the depression of evoked EPSCs and the decrease in the frequency of spontaneous EPSCs. An inhibitor for receptor tyrosine kinases, K252a, antagonised the action of BDNF, suggesting an involvement of BDNF receptors, TrkB. These results suggest that BDNF prevents low-frequency inputs from inducing LTD of excitatory synaptic transmission through presynaptic mechanisms in the developing visual cortex. PMID:10747192

An N-methyl-D-aspartate receptor-independent excitatory action of partial reduction of extracellular [Mg2+] in CA1-region of rat hippocampal slices.

PubMed

Hamon, B; Stanton, P K; Heinemann, U

1987-03-31

Partial reduction of [Mg2+]o from 2 to 1 mM markedly enhanced neuronal responses evoked by Schaffer collateral-commissural fiber stimulation in the CA1-region of rat hippocampal slices. The amplitude of extracellular population potentials recorded in the CA1-pyramidal cell layer and maximum dV/dt of extracellular population EPSP's recorded in the CA1-pyramidal apical dendritic layer were both increased. However, unlike findings from slices where Mg2+ was completely removed from the bathing medium, there was no spontaneous or evoked epileptiform activity, and the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (2-APV) did not antagonize the enhancement of evoked responses. These results indicate that, in addition to the participation of NMDA receptors in the epileptiform activity observed when Mg2+ is completely removed from the bathing medium, there is also an NMDA receptor-independent excitatory action of partial reduction of [Mg2+]o in hippocampal slices.

Mirror Neurons Modeled Through Spike-Timing-Dependent Plasticity are Affected by Channelopathies Associated with Autism Spectrum Disorder.

PubMed

Antunes, Gabriela; Faria da Silva, Samuel F; Simoes de Souza, Fabio M

2018-06-01

Mirror neurons fire action potentials both when the agent performs a certain behavior and watches someone performing a similar action. Here, we present an original mirror neuron model based on the spike-timing-dependent plasticity (STDP) between two morpho-electrical models of neocortical pyramidal neurons. Both neurons fired spontaneously with basal firing rate that follows a Poisson distribution, and the STDP between them was modeled by the triplet algorithm. Our simulation results demonstrated that STDP is sufficient for the rise of mirror neuron function between the pairs of neocortical neurons. This is a proof of concept that pairs of neocortical neurons associating sensory inputs to motor outputs could operate like mirror neurons. In addition, we used the mirror neuron model to investigate whether channelopathies associated with autism spectrum disorder could impair the modeled mirror function. Our simulation results showed that impaired hyperpolarization-activated cationic currents (Ih) affected the mirror function between the pairs of neocortical neurons coupled by STDP.

Cortical neurons and networks are dormant but fully responsive during isoelectric brain state.

PubMed

Altwegg-Boussac, Tristan; Schramm, Adrien E; Ballestero, Jimena; Grosselin, Fanny; Chavez, Mario; Lecas, Sarah; Baulac, Michel; Naccache, Lionel; Demeret, Sophie; Navarro, Vincent; Mahon, Séverine; Charpier, Stéphane

2017-09-01

A continuous isoelectric electroencephalogram reflects an interruption of endogenously-generated activity in cortical networks and systematically results in a complete dissolution of conscious processes. This electro-cerebral inactivity occurs during various brain disorders, including hypothermia, drug intoxication, long-lasting anoxia and brain trauma. It can also be induced in a therapeutic context, following the administration of high doses of barbiturate-derived compounds, to interrupt a hyper-refractory status epilepticus. Although altered sensory responses can be occasionally observed on an isoelectric electroencephalogram, the electrical membrane properties and synaptic responses of individual neurons during this cerebral state remain largely unknown. The aim of the present study was to characterize the intracellular correlates of a barbiturate-induced isoelectric electroencephalogram and to analyse the sensory-evoked synaptic responses that can emerge from a brain deprived of spontaneous electrical activity. We first examined the sensory responsiveness from patients suffering from intractable status epilepticus and treated by administration of thiopental. Multimodal sensory responses could be evoked on the flat electroencephalogram, including visually-evoked potentials that were significantly amplified and delayed, with a high trial-to-trial reproducibility compared to awake healthy subjects. Using an analogous pharmacological procedure to induce prolonged electro-cerebral inactivity in the rat, we could describe its cortical and subcortical intracellular counterparts. Neocortical, hippocampal and thalamo-cortical neurons were all silent during the isoelectric state and displayed a flat membrane potential significantly hyperpolarized compared with spontaneously active control states. Nonetheless, all recorded neurons could fire action potentials in response to intracellularly injected depolarizing current pulses and their specific intrinsic electrophysiological features were preserved. Manipulations of the membrane potential and intracellular injection of chloride in neocortical neurons failed to reveal an augmented synaptic inhibition during the isoelectric condition. Consistent with the sensory responses recorded from comatose patients, large and highly reproducible somatosensory-evoked potentials could be generated on the inactive electrocorticogram in rats. Intracellular recordings revealed that the underlying neocortical pyramidal cells responded to sensory stimuli by complex synaptic potentials able to trigger action potentials. As in patients, sensory responses in the isoelectric state were delayed compared to control responses and exhibited an elevated reliability during repeated stimuli. Our findings demonstrate that during prolonged isoelectric brain state neurons and synaptic networks are dormant rather than excessively inhibited, conserving their intrinsic properties and their ability to integrate and propagate environmental stimuli. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

ParamAP: Standardized Parameterization of Sinoatrial Node Myocyte Action Potentials.

PubMed

Rickert, Christian; Proenza, Catherine

2017-08-22

Sinoatrial node myocytes act as cardiac pacemaker cells by generating spontaneous action potentials (APs). Much information is encoded in sinoatrial AP waveforms, but both the analysis and the comparison of AP parameters between studies is hindered by the lack of standardized parameter definitions and the absence of automated analysis tools. Here we introduce ParamAP, a standalone cross-platform computational tool that uses a template-free detection algorithm to automatically identify and parameterize APs from text input files. ParamAP employs a graphic user interface with automatic and user-customizable input modes, and it outputs data files in text and PDF formats. ParamAP returns a total of 16 AP waveform parameters including time intervals such as the AP duration, membrane potentials such as the maximum diastolic potential, and rates of change of the membrane potential such as the diastolic depolarization rate. ParamAP provides a robust AP detection algorithm in combination with a standardized AP parameter analysis over a wide range of AP waveforms and firing rates, owing in part to the use of an iterative algorithm for the determination of the threshold potential and the diastolic depolarization rate that is independent of the maximum upstroke velocity, a parameter that can vary significantly among sinoatrial APs. Because ParamAP is implemented in Python 3, it is also highly customizable and extensible. In conclusion, ParamAP is a powerful computational tool that facilitates quantitative analysis and enables comparison of sinoatrial APs by standardizing parameter definitions and providing an automated work flow. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Spontaneous and posed facial expression in Parkinson's disease.

PubMed

Smith, M C; Smith, M K; Ellgring, H

1996-09-01

Spontaneous and posed emotional facial expressions in individuals with Parkinson's disease (PD, n = 12) were compared with those of healthy age-matched controls (n = 12). The intensity and amount of facial expression in PD patients were expected to be reduced for spontaneous but not posed expressions. Emotional stimuli were video clips selected from films, 2-5 min in duration, designed to elicit feelings of happiness, sadness, fear, disgust, or anger. Facial movements were coded using Ekman and Friesen's (1978) Facial Action Coding System (FACS). In addition, participants rated their emotional experience on 9-point Likert scales. The PD group showed significantly less overall facial reactivity than did controls when viewing the films. The predicted Group X Condition (spontaneous vs. posed) interaction effect on smile intensity was found when PD participants with more severe disease were compared with those with milder disease and with controls. In contrast, ratings of emotional experience were similar for both groups. Depression was positively associated with emotion rating but not with measures of facial activity. Spontaneous facial expression appears to be selectively affected in PD, whereas posed expression and emotional experience remain relatively intact.

Sowing the seeds of stereotypes: Spontaneous inferences about groups.

PubMed

Hamilton, David L; Chen, Jacqueline M; Ko, Deborah M; Winczewski, Lauren; Banerji, Ishani; Thurston, Joel A

2015-10-01

Although dispositional inferences may be consciously drawn from the trait implications of observed behavior, abundant research has shown that people also spontaneously infer trait dispositions simply in the process of comprehending behavior. These spontaneous trait inferences (STIs) can occur without intention or awareness. All research on STIs has studied STIs based on behaviors of individual persons. Yet important aspects of social life occur in groups, and people regularly perceive groups engaging in coordinated action. We propose that perceivers make spontaneous trait inferences about groups (STIGs), parallel to the STIs formed about individuals. In 5 experiments we showed that (a) perceivers made STIGs comparable with STIs about individuals (based on the same behaviors), (b) a cognitive load manipulation did not affect the occurrence of STIGs, (c) STIGs occurred for groups varying in entitativity, (d) STIGs influenced perceivers' impression ratings of those groups, and (e) STIG-based group impressions generalized to new group members. These experiments provide the first evidence for STIGs, a process that may contribute to the formation of spontaneous group impressions. Implications for stereotype formation are discussed. (c) 2015 APA, all rights reserved).

Counterfactual Thinking Deficit in Huntington’s Disease

PubMed Central

Solca, Federica; Poletti, Barbara; Zago, Stefano; Crespi, Chiara; Sassone, Francesca; Lafronza, Annalisa; Maraschi, Anna Maria; Sassone, Jenny; Silani, Vincenzo; Ciammola, Andrea

2015-01-01

Background and Objective Counterfactual thinking (CFT) refers to the generation of mental simulations of alternatives to past events, actions and outcomes. CFT is a pervasive cognitive feature in every-day life and is closely related to decision-making, planning and problem-solving – all of which are cognitive processes linked to unimpaired frontal lobe functioning. Huntington’s Disease (HD) is a neurodegenerative disorder characterised by motor, behavioral and cognitive dysfunctions. Because an impairment in frontal and executive functions has been described in HD, we hypothesised that HD patients may have a CFT impairment. Methods Tests of spontaneous counterfactual thoughts and counterfactual-derived inferences were administered to 24 symptomatic HD patients and 24 age- and sex-matched healthy subjects. Results Our results show a significant impairment in the spontaneous generation of CFT and low performance on the Counterfactual Inference Test (CIT) in HD patients. Low performance on the spontaneous CFT test significantly correlates with impaired attention abilities, verbal fluency and frontal lobe efficiency, as measured by Trail Making Test – Part A, Phonemic Verbal Fluency Test and FAB. Conclusions Spontaneous CFT and the use of this type of reasoning are impaired in HD patients. This deficit may be related to frontal lobe dysfunction, which is a hallmark of HD. Because CFT has a pervasive role in patients’ daily lives regarding their planning, decision making and problem solving skills, cognitive rehabilitation may improve HD patients’ ability to analyse current behaviors and future actions. PMID:26070155

Multiple-stage structure transformation of organic-inorganic hybrid perovskite CH 3 NH 3 PbI 3

DOE PAGES

Chen, Qiong; Liu, Henan; Kim, Hui -Seon; ...

2016-09-15

In this study, by performing spatially resolved Raman and photoluminescence spectroscopy with varying excitation wavelength, density, and data acquisition parameters, we achieve a unified understanding towards the spectroscopy signatures of the organic-inorganic hybrid perovskite, transforming from the pristine state (CH 3NH 3PbI 3) to the fully degraded state (i.e., PbI 2) for samples with varying crystalline domain size from mesoscopic scale (approximately 100 nm) to macroscopic size (centimeters), synthesized by three different techniques. We show that the hybrid perovskite exhibits multiple stages of structure transformation occurring either spontaneously or under light illumination, with exceptionally high sensitivity to the illumination conditionsmore » (e.g., power, illumination time, and interruption pattern). We highlight four transformation stages (stages I-IV, with stage I being the pristine state) along either the spontaneous or photoinduced degradation path exhibiting distinctly different Raman spectroscopy features at each stage, and point out that previously reported Raman spectra in the literature reflect highly degraded structures of either stage III or stage IV. Additional characteristic optical features of partially degraded materials under the joint action of spontaneous and photodegradation are also given. This study offers reliable benchmark results for understanding the intrinsic material properties and structure transformation of this unique category of hybrid materials, and the findings are pertinently important to a wide range of potential applications where the hybrid material is expected to function in greatly different environment and light-matter interaction conditions.« less

Multiple-Stage Structure Transformation of Organic-Inorganic Hybrid Perovskite CH3NH3PbI3

NASA Astrophysics Data System (ADS)

Chen, Qiong; Liu, Henan; Kim, Hui-Seon; Liu, Yucheng; Yang, Mengjin; Yue, Naili; Ren, Gang; Zhu, Kai; Liu, Shengzhong; Park, Nam-Gyu; Zhang, Yong

2016-07-01

By performing spatially resolved Raman and photoluminescence spectroscopy with varying excitation wavelength, density, and data acquisition parameters, we achieve a unified understanding towards the spectroscopy signatures of the organic-inorganic hybrid perovskite, transforming from the pristine state (CH3NH3PbI3 ) to the fully degraded state (i.e., PbI2 ) for samples with varying crystalline domain size from mesoscopic scale (approximately 100 nm) to macroscopic size (centimeters), synthesized by three different techniques. We show that the hybrid perovskite exhibits multiple stages of structure transformation occurring either spontaneously or under light illumination, with exceptionally high sensitivity to the illumination conditions (e.g., power, illumination time, and interruption pattern). We highlight four transformation stages (stages I-IV, with stage I being the pristine state) along either the spontaneous or photoinduced degradation path exhibiting distinctly different Raman spectroscopy features at each stage, and point out that previously reported Raman spectra in the literature reflect highly degraded structures of either stage III or stage IV. Additional characteristic optical features of partially degraded materials under the joint action of spontaneous and photodegradation are also given. This study offers reliable benchmark results for understanding the intrinsic material properties and structure transformation of this unique category of hybrid materials, and the findings are pertinently important to a wide range of potential applications where the hybrid material is expected to function in greatly different environment and light-matter interaction conditions.

NbActiv4 medium improvement to Neurobasal/B27 increases neuron synapse densities and network spike rates on multielectrode arrays.

PubMed

Brewer, Gregory J; Boehler, Michael D; Jones, Torrie T; Wheeler, Bruce C

2008-05-30

The most interesting property of neurons is their long-distance propagation of signals as spiking action potentials. Since 1993, Neurobasal/B27 has been used as a serum-free medium optimized for hippocampal neuron survival. Neurons on microelectrode arrays (MEA) were used as an assay system to increase spontaneous spike rates in media of different compositions. We find spike rates of 0.5 s(-1) (Hz) for rat embryonic hippocampal neurons cultured in Neurobasal/B27, lower than cultures in serum-based media and offering an opportunity for improvement. NbActiv4 was formulated by addition of creatine, cholesterol and estrogen to Neurobasal/B27 that synergistically produced an eightfold increase in spontaneous spike activity. The increased activity with NbActiv4 correlated with a twofold increase in immunoreactive synaptophysin bright puncta and GluR1 total puncta. Characteristic of synaptic scaling, immunoreactive GABAAbeta puncta also increased 1.5-fold and NMDA-R1 puncta increased 1.8-fold. Neuron survival in NbActiv4 equaled that in Neurobasal/B27, but with slightly higher astroglia. Resting respiratory demand was decreased and demand capacity was increased in NbActiv4, indicating less stress and higher efficiency. These results show that NbActiv4 is an improvement to Neurobasal/B27 for cultured networks with an increased density of synapses and transmitter receptors which produces higher spontaneous spike rates in neuron networks.

Regulation of persistent sodium currents by glycogen synthase kinase 3 encodes daily rhythms of neuronal excitability

NASA Astrophysics Data System (ADS)

Paul, Jodi R.; Dewoskin, Daniel; McMeekin, Laura J.; Cowell, Rita M.; Forger, Daniel B.; Gamble, Karen L.

2016-11-01

How neurons encode intracellular biochemical signalling cascades into electrical signals is not fully understood. Neurons in the central circadian clock in mammals provide a model system to investigate electrical encoding of biochemical timing signals. Here, using experimental and modelling approaches, we show how the activation of glycogen synthase kinase 3 (GSK3) contributes to neuronal excitability through regulation of the persistent sodium current (INaP). INaP exhibits a day/night difference in peak magnitude and is regulated by GSK3. Using mathematical modelling, we predict and confirm that GSK3 activation of INaP affects the action potential afterhyperpolarization, which increases the spontaneous firing rate without affecting the resting membrane potential. Together, these results demonstrate a crucial link between the molecular circadian clock and electrical activity, providing examples of kinase regulation of electrical activity and the propagation of intracellular signals in neuronal networks.

Novel concept of washing for microfluidic paper-based analytical devices based on capillary force of paper substrates.

PubMed

Mohammadi, Saeed; Busa, Lori Shayne Alamo; Maeki, Masatoshi; Mohamadi, Reza M; Ishida, Akihiko; Tani, Hirofumi; Tokeshi, Manabu

2016-11-01

A novel washing technique for microfluidic paper-based analytical devices (μPADs) that is based on the spontaneous capillary action of paper and eliminates unbound antigen and antibody in a sandwich immunoassay is reported. Liquids can flow through a porous medium (such as paper) in the absence of external pressure as a result of capillary action. Uniform results were achieved when washing a paper substrate in a PDMS holder which was integrated with a cartridge absorber acting as a porous medium. Our study demonstrated that applying this washing technique would allow μPADs to become the least expensive microfluidic device platform with high reproducibility and sensitivity. In a model μPAD assay that utilized this novel washing technique, C-reactive protein (CRP) was detected with a limit of detection (LOD) of 5 μg mL -1 . Graphical Abstract A novel washing technique for microfluidic paper-based analytical devices (μPADs) that is based on the spontaneous capillary action of paper and eliminates unbound antigen and antibody in a sandwich immunoassay is reported.

Markets on Networks

NASA Astrophysics Data System (ADS)

Toroczkai, Zoltan; Anghel, Marian; Bassler, Kevin; Korniss, Gyorgy

2003-03-01

The dynamics of human, and most biological populations is characterized by competition for resources. By its own nature, this dynamics creates the group of "elites", formed by those agents who have strategies that are the most successful in the given situation, and therefore the rest of the agents will tend to follow, imitate, or interact with them, creating a social structure of leadership in the agent society. These inter-agent communications generate a complex social network with small-world character which itself forms the substrate for a second network, the action network. The latter is a highly dynamic, adaptive, directed network, defined by those inter-agent communication links on the substrate along which the passed information /prediction is acted upon by the other agents. By using the minority game for competition dynamics, here we show that when the substrate network is highly connected, the action network spontaneously develops hubs with a broad distribution of out-degrees, defining a robust leadership structure that is scale-free. Furthermore, in certain, realistic parameter ranges, facilitated by information passing on the action network, agents can spontaneously generate a high degree of cooperation making the collective almost maximally efficient.

Reduction of opioid withdrawal and potentiation of acute opioid analgesia by systemic AV411 (ibudilast)

PubMed Central

Hutchinson, Mark R.; Lewis, Susannah S.; Coats, Benjamen D.; Skyba, David A.; Crysdale, Nicole Y.; Berkelhammer, Debra L.; Brzeski, Anita; Northcutt, Alexis; Vietz, Christine M.; Judd, Charles M.; Maier, Steven F.; Watkins, Linda R.; Johnson, Kirk W.

2009-01-01

Morphine-induced glial proinflammatory responses have been documented to contribute to tolerance to opioid analgesia. Here, we examined whether drugs previously shown to suppress glial proinflammatory responses can alter other clinically relevant opioid effects; namely, withdrawal or acute analgesia. AV411 (ibudilast) and minocycline, drugs with distinct mechanisms of action that result in attenuation of glial proinflammatory responses, each reduced naloxone-precipitated withdrawal. Analysis of brain nuclei associated with opioid withdrawal revealed that morphine altered expression of glial activation markers, cytokines, chemokines, and a neurotrophic factor. AV411 attenuated many of these morphine-induced effects. AV411 also protected against spontaneous withdrawal-induced hyperactivity and weight loss recorded across a 12-day timecourse. Notably, in the spontaneous withdrawal study, AV411 treatment was delayed relative to the start of the morphine regimen so to also test whether AV411 could still be effective in the face of established morphine dependence, which it was. AV411 did not simply attenuate all opioid effects, as co-administering AV411 with morphine or oxycodone caused 3-to-5-fold increases in acute analgesic potency, as revealed by leftward shifts in the analgesic dose response curves. Timecourse analyses revealed that plasma morphine levels were not altered by AV411, suggestive that potentiated analgesia was not simply due to prolongation of morphine exposure or increased plasma concentrations. These data support and extend similar potentiation of acute opioid analgesia by minocycline, again providing converging lines of evidence of glial involvement. Hence, suppression of glial proinflammatory responses can significantly reduce opioid withdrawal, whilst improving analgesia. PMID:18938237

A cephalic projection neuron involved in locomotion is dye coupled to the dopaminergic neural network in the medicinal leech.

PubMed

Crisp, Kevin M; Mesce, Karen A

2004-12-01

It is widely appreciated that the selection and modulation of locomotor circuits are dependent on the actions of higher-order projection neurons. In the leech, Hirudo medicinalis, locomotion is modulated by a number of cephalic projection neurons that descend from the subesophageal ganglion in the head. Specifically, descending brain interneuron Tr2 functions as a command-like neuron that can terminate or sometimes trigger fictive swimming. In this study, we demonstrate that Tr2 is dye coupled to the dopaminergic neural network distributed in the head brain. These findings represent the first anatomical evidence in support of dopamine (DA) playing a role in the modulation of locomotion in the leech. In addition, we have determined that bath application of DA to the brain and entire nerve cord reliably and rapidly terminates swimming in all preparations exhibiting fictive swimming. By contrast, DA application to nerve cords expressing ongoing fictive crawling does not inhibit this motor rhythm. Furthermore, we show that Tr2 receives rhythmic feedback from the crawl central pattern generator. For example, Tr2 receives inhibitory post-synaptic potentials during the elongation phase of each crawl cycle. When crawling is not expressed, spontaneous inhibitory post-synaptic potentials in Tr2 correlate in time with spontaneous excitatory post-synaptic potentials in the CV motor neuron, a circular muscle excitor that bursts during the elongation phase of crawling. Our data are consistent with the idea that DA biases the nervous system to produce locomotion in the form of crawling.

Rapid fusion between mesenchymal stem cells and cardiomyocytes yields electrically active, non-contractile hybrid cells.

PubMed

Shadrin, Ilya Y; Yoon, Woohyun; Li, Liqing; Shepherd, Neal; Bursac, Nenad

2015-07-10

Cardiac cell therapies involving bone marrow-derived human mesenchymal stem cells (hMSCs) have shown promising results, although their mechanisms of action are still poorly understood. Here, we investigated direct interactions between hMSCs and cardiomyocytes in vitro. Using a genetic Ca(2+) indicator gCaMP3 to efficiently label hMSCs in co-cultures with neonatal rat ventricular myocytes (NRVMs), we determined that 25-40% of hMSCs (from 4 independent donors) acquired periodic Ca(2+) transients and cardiac markers through spontaneous fusion with NRVMs. Sharp electrode and voltage-clamp recordings in fused cells showed action potential properties and Ca(2+) current amplitudes in between those of non-fused hMSCs and NRVMs. Time-lapse video-microscopy revealed the first direct evidence of active fusion between hMSCs and NRVMs within several hours of co-culture. Application of blebbistatin, nifedipine or verapamil caused complete and reversible inhibition of fusion, suggesting potential roles for actomyosin bridging and Ca(2+) channels in the fusion process. Immunostaining for Cx43, Ki67, and sarcomeric α-actinin showed that fused cells remain strongly coupled to surrounding NRVMs, but downregulate sarcomeric structures over time, acquiring a non-proliferative and non-contractile phenotype. Overall, these results describe the phenotype and mechanisms of hybrid cell formation via fusion of hMSCs and cardiomyocytes with potential implications for cardiac cell therapy.

Selective depolarization of the muscle membrane in frog nerve-muscle preparations by a chromatographically purified extract of the dinoflagellate Ostreopsis lenticularis

PubMed Central

Meunier, Frédéric A; Mercado, José A; Molgó, Jordi; Tosteson, Thomas R; Escalona de Motta, Gladys

1997-01-01

The actions of a chromatographically identified extract of the marine dinoflagellate Ostreopsis lenticularis, named ostreotoxin-3 (OTX-3), were studied on frog isolated neuromuscular preparations. OTX-3 (1–10 μg ml−1) applied to cutaneous pectoris nerve-muscle preparations depolarized skeletal muscle fibres and caused spontaneous contractions. The depolarization was neither reversed by prolonged washing nor by (+)-tubocurarine. OTX-3 decreased the amplitude of miniature end plate potentials (m.e.p.ps) but did not affect their frequency. Extracellular recording of compound action potentials revealed that OTX-3 affected neither excitability nor conduction along intramuscular nerve branches. End-plate potentials (e.p.ps) elicited by nerve stimulation were reduced in amplitude by OTX-3 and even showed reversed polarity in junctions deeply depolarized by the toxin. Membrane depolarization induced by OTX-3 was decreased about 70% in muscles pretreated for 30 min with 10 μM tetrodotoxin. In contrast, muscles pretreated with 5 μM μ-conotoxin GIIIA were completely insensitive to OTX-3-induced depolarization. OTX-3 did not affect e.p.p. amplitude and the quantal content of e.p.ps in junctions in which muscle depolarization was abolished by μ-conotoxin GIIIA. OTX-3 is a novel type of sodium-channel activating toxin that discriminates between nerve and skeletal muscle membranes. PMID:9249261

Biological relevance of decamethylcyclopentasiloxane (D5) induced rat uterine endometrial adenocarcinoma tumorigenesis: Mode of action and relevance to humans.

PubMed

Klaunig, James E; Dekant, Wolfgang; Plotzke, Kathy; Scialli, Anthony R

2016-02-01

Decamethylcyclopentasiloxane (D5) is a cyclic siloxane used in the production and formulation of consumer products with potential exposure to manufacturing workers, consumer, and the general public. Following a combined 2-year inhalation chronic bioassay performed in Fischer 344 (F344) rats, an increase in uterine endometrial adenocarcinomas was noted at the highest concentration to which animals were exposed. No other neoplasms were detected. In this study, a dose of 160 ppm produced an incidence of 8% endometrial adenocarcinomas. Based on a number of experimental studies with D5, the current manuscript examines the biological relevance and possible modes of action for the uterine endometrial adenocarcinomas observed in the rat following chronic exposure to D5. Variable rates of spontaneous uterine endometrial adenocarcinomas have been reported for untreated F344 CrlBr rats. As such, we concluded that the slight increase in uterine endometrial adenocarcinomas observed in the D5 chronic bioassay might not be the result of D5 exposure but may be related to variability of the spontaneous tumor incidence in this strain of rat. However, if the uterine endometrial adenocarcinomas are related to D5-exposure, alteration in the estrous cycle in the aging F344 rat is the most likely mode of action. D5 is not genotoxic or estrogenic. The alteration in the estrous cycle is caused by a decrease in progesterone with an increase in the estrogen:progesterone ratio most likely induced by a decrease in prolactin concentration. Available data support that exposure to D5 influences prolactin concentration. Although the effects on prolactin concentrations in a number of experiments were not always consistent, the available data support the conclusion that D5 is acting via a dopamine receptor agonist-like mechanism to alter the pituitary control of the estrous cycle. In further support of this mode of action, studies in F344 aged animals showed that the effects of D5 on estrous cyclicity produced a response consistent with a dopamine-like effect and further suggest that D5 is accelerating the aging of the reproductive endocrine system in the F344 rat utilized in this study. This mode of action for uterine endometrial adenocarcinoma tumorigenesis is not relevant for humans. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Transient receptor potential ankyrin 1 channels are involved in spontaneous peptide hormone release from astrocytes.

PubMed

Takizawa, Mai; Harada, Kazuki; Nakamura, Kazuaki; Tsuboi, Takashi

2018-07-02

Astrocytes, a large population of glial cells, detect neurotransmitters and respond by increasing intracellular Ca 2+ concentration ([Ca 2+ ] i ) and releasing chemical molecules called gliotransmitters. Recently discovered Ca 2+ influx through transient receptor potential ankyrin 1 (TRPA1) channels is reported to cause spontaneous [Ca 2+ ] i increase in astrocytes. While several physiological functions of TRPA1-mediated spontaneous Ca 2+ signal have been revealed, relation with gliotransmitter release, especially peptide hormone exocytosis is largely unknown. We therefore explored the [Ca 2+ ] i and exocytosis dynamics in rat astrocyte cell line C6 cells and primary astrocytes. TRPA1-mediated spontaneous [Ca 2+ ] i transients were observed in both C6 cells and primary astrocytes. Total internal reflection fluorescence microscopy revealed that Venus-tagged brain-derived neurotrophic factor and neuropeptide Y were released spontaneously from astrocytes. Activation of TRPA1 channels enhanced the frequency of peptide hormone exocytosis, and inhibition of TRPA1 channels decreased the number of peptide hormone exocytosis. These results suggest that TRPA1-mediated spontaneous [Ca 2+ ] i increase modulates the spontaneous release of peptide hormones from astrocytes. Copyright © 2018 Elsevier Inc. All rights reserved.

Association study of estrogen receptor alpha gene polymorphisms with spontaneous abortion: is this a possible reason for unexplained spontaneous abortion?

PubMed

Anousha, Negin; Hossein-Nezhad, Arash; Biramijamal, Firouzeh; Rahmani, Ali; Maghbooli, Zhila; Aghababaei, Elahe; Nemati, Shahram

2013-01-01

Estrogen plays a crucial role in fetal and placental development through estrogen receptors. Association of estrogen receptor alpha gene (ESR1) polymorphisms with spontaneous abortion has been shown in some studies. Our main goal was to study the potential association of spontaneous abortion with the ESR1 gene variations (PvuII and XbaI) in fetal tissue. Totally, 161 samples were recruited including 80 samples of formalin-fixed paraffin-embedded fetal tissue from spontaneous abortion and 81 samples of normal term placental tissue. The restriction fragment length polymorphism (RFLP) method was performed for genotyping the rs2234693 (A/G XbaI) and rs9340799 (T/C PvuII) single nucleotide polymorphisms located in intron 1 of ESR1. The results have been confirmed by DNA sequencing analysis. The different genotypes distribution was detected in two study groups. Haplotype analysis indicated that ppxx is protective genotype against spontaneous abortion (P = 0.01). In conclusion, the potential role of ESR1 genetic variation in spontaneous abortion might be valuable in high-risk subjects, and that needs to be confirmed with future studies.

Association Study of Estrogen Receptor Alpha Gene Polymorphisms with Spontaneous Abortion: Is This a Possible Reason for Unexplained Spontaneous Abortion?

PubMed Central

Anousha, Negin; Hossein-Nezhad, Arash; Biramijamal, Firouzeh; Rahmani, Ali; Maghbooli, Zhila; Aghababaei, Elahe; Nemati, Shahram

2013-01-01

Estrogen plays a crucial role in fetal and placental development through estrogen receptors. Association of estrogen receptor alpha gene (ESR1) polymorphisms with spontaneous abortion has been shown in some studies. Our main goal was to study the potential association of spontaneous abortion with the ESR1 gene variations (PvuII and XbaI) in fetal tissue. Totally, 161 samples were recruited including 80 samples of formalin-fixed paraffin-embedded fetal tissue from spontaneous abortion and 81 samples of normal term placental tissue. The restriction fragment length polymorphism (RFLP) method was performed for genotyping the rs2234693 (A/G XbaI) and rs9340799 (T/C PvuII) single nucleotide polymorphisms located in intron 1 of ESR1. The results have been confirmed by DNA sequencing analysis. The different genotypes distribution was detected in two study groups. Haplotype analysis indicated that ppxx is protective genotype against spontaneous abortion (P = 0.01). In conclusion, the potential role of ESR1 genetic variation in spontaneous abortion might be valuable in high-risk subjects, and that needs to be confirmed with future studies. PMID:24228243

DELTAMETHRIN AND PERMETHRIN DECREASE SPONTANEOUS NETWORK ACTIVITY IN VITRO.

EPA Science Inventory

ABSTRACT BODY: Pyrethroid insecticides alter inactivation of voltage-sensitive sodium channels, an action that underlies their insecticidal and neurotoxicological properties. How alterations in sodium channel function give rise to the characteristic signs of pyrethroid intoxicati...

[The role of remodeling complexes CHD1 and ISWI in spontaneous and UV-induced mutagenesis control in yeast Saccharomyces cerevisiae].

PubMed

Evstiukhina, T A; Alekseeva, E A; Fedorov, D V; Peshekhonov, V T; Korolev, V G

2017-02-01

Chromatin remodulators are special multiprotein machines capable of transforming the structure, constitution, and positioning of nucleosomes on DNA. Biochemical activities of remodeling complexes CHD1 and ISWI from the SWI2/SNF2 family are well established. They ensure correct positioning of nucleosomes along the genome, which is probably critical for genome stability, in particular, after action of polymerases, repair enzymes, and transcription. In this paper, we show that single mutations in genes ISW1, ISW2, and CHD1 weakly affect repair and mutagenic processes in yeast cells. At the same time, there are differences in the effect of these mutations on spontaneous mutation levels, which indicates certain specificity of action of protein complexes ISW1, ISW2, and CHD1 on expression of different genes that control repair and mutation processes in yeast.

[History of "special therapeutic directions": the example of homeopathy].

PubMed

Hopff, W H

1996-04-01

As for generally accepted therapeutic methods, the "special methods" may appear to be effective due to spontaneous recovery provided by nature. A great number of sceptical physicians are aware of this fact. The pharmacologist works continuously to differentiate effects directly caused by medical treatments - mainly drugs - from effects resulting from spontaneous recovery. This is one of the most difficult problems in medical treatment. As a representative example of all "special methods", we concentrate here on the history of homeopathy. As is generally known, there is no conformity in homeopathy, for example monotherapy versus therapy with complex homeopathic products; refusing the simile-rule; treatment with high potencies versus treatment with low potencies; classic versus scholastic homeopathy. The number of homeopathies really equals the number of homeopathic physicians. For this reason, instruction in homeopathy on the academic level is impossible. In addition, we have to forget all natural laws only to prove that "potentiation" may be true. Therapeutic success due purely to chance may be explained rationally and is occasionally seen in all other "special methods". The theories of homeopaths for the action with homeopathic products are neither in accordance with our natural laws nor comply with a rational philosophy.

Assessment of the Tumorigenic Potential of Spontaneously Immortalized and hTERT-Immortalized Cultured Dental Pulp Stem Cells

PubMed Central

Wilson, Ryan; Urraca, Nora; Skobowiat, Cezary; Hope, Kevin A.; Miravalle, Leticia; Chamberlin, Reed; Donaldson, Martin; Seagroves, Tiffany N.

2015-01-01

Dental pulp stem cells (DPSCs) provide an exciting new avenue to study neurogenetic disorders. DPSCs are neural crest-derived cells with the ability to differentiate into numerous tissues including neurons. The therapeutic potential of stem cell-derived lines exposed to culturing ex vivo before reintroduction into patients could be limited if the cultured cells acquired tumorigenic potential. We tested whether DPSCs that spontaneously immortalized in culture acquired features of transformed cells. We analyzed immortalized DPSCs for anchorage-independent growth, genomic instability, and ability to differentiate into neurons. Finally, we tested both spontaneously immortalized and human telomerase reverse transcriptase (hTERT)-immortalized DPSC lines for the ability to form tumors in immunocompromised animals. Although we observed increased colony-forming potential in soft agar for the spontaneously immortalized and hTERT-immortalized DPSC lines relative to low-passage DPSC, no tumors were detected from any of the DPSC lines tested. We noticed some genomic instability in hTERT-immortalized DPSCs but not in the spontaneously immortalized lines tested. We determined that immortalized DPSC lines generated in our laboratory, whether spontaneously or induced, have not acquired the potential to form tumors in mice. These data suggest cultured DPSC lines that can be differentiated into neurons may be safe for future in vivo therapy for neurobiological diseases. Significance This study demonstrated that immortalized dental pulp stem cells (DPSCs) do not form tumors in animals and that immortalized DPSCs can be differentiated into neurons in culture. These results lend support to the use of primary and immortalized DPSCs for future therapeutic approaches to treatment of neurobiological diseases. PMID:26032749

Simulation of Arrhythmogenic Effect of Rogue RyRs in Failing Heart by Using a Coupled Model

PubMed Central

Lu, Luyao; Xia, Ling; Zhu, Xiuwei

2012-01-01

Cardiac cells with heart failure are usually characterized by impairment of Ca2+ handling with smaller SR Ca2+ store and high risk of triggered activities. In this study, we developed a coupled model by integrating the spatiotemporal Ca2+ reaction-diffusion system into the cellular electrophysiological model. With the coupled model, the subcellular Ca2+ dynamics and global cellular electrophysiology could be simultaneously traced. The proposed coupled model was then applied to study the effects of rogue RyRs on Ca2+ cycling and membrane potential in failing heart. The simulation results suggested that, in the presence of rogue RyRs, Ca2+ dynamics is unstable and Ca2+ waves are prone to be initiated spontaneously. These release events would elevate the membrane potential substantially which might induce delayed afterdepolarizations or triggered action potentials. Moreover, the variation of membrane potential depolarization is indicated to be dependent on the distribution density of rogue RyR channels. This study provides a new possible arrhythmogenic mechanism for heart failure from subcellular to cellular level. PMID:23056145

Overcoming the unhealthy pursuit of thinness: reaction to the Québec Charter for a Healthy and Diverse Body Image.

PubMed

Gauvin, Lise; Steiger, Howard

2012-08-01

We examined the population reach, acceptability, and perceived potential of an initiative that developed a promotional tool for a healthy body image, the Québec Charter for a Healthy and Diverse Body Image. The Charter, developed through consensus building by a multisectoral, government-led task force, outlined actions to be undertaken by organizations or citizens to reduce media pressures favoring thinness. Six months after the Charter's launch, we surveyed 1003 Québec residents aged 18 years or older about their knowledge of the Charter, their willingness to adhere to it, and their perceptions of its potential. After minimal prompting, more than 35% of respondents recognized the Charter. About 33.7% were very favorable toward personally adhering to the Charter and 32.7% perceived the Charter as having high potential to sensitize people to negative consequences of disordered eating. Women showed greater likelihood and people with lesser education showed lower likelihood of spontaneous recognition. An initiative involving the creation of a body image Charter reaches a substantial portion of adults and is viewed as acceptable and potentially influential.

Hydrogen-bonded intermediates and transition states during spontaneous and acid-catalyzed hydrolysis of the carcinogen (+)-anti-BPDE.

PubMed

Palenik, Mark C; Rodriguez, Jorge H

2014-07-07

Understanding mechanisms of (+)-anti-BPDE detoxification is crucial for combating its mutagenic and potent carcinogenic action. However, energetic-structural correlations of reaction intermediates and transition states during detoxification via hydrolysis are poorly understood. To gain mechanistic insight we have computationally characterized intermediate and transition species associated with spontaneous and general-acid catalyzed hydrolysis of (+)-anti-BPDE. We studied the role of cacodylic acid as a proton donor in the rate limiting step. The computed activation energy (ΔG‡) is in agreement with the experimental value for hydrolysis in a sodium cacodylate buffer. Both types of, spontaneous and acid catalyzed, BPDE hydrolysis can proceed through low-entropy hydrogen bonded intermediates prior to formation of transition states whose energies determine reaction activation barriers and rates.

Spontaneous cortical activity reveals hallmarks of an optimal internal model of the environment.

PubMed

Berkes, Pietro; Orbán, Gergo; Lengyel, Máté; Fiser, József

2011-01-07

The brain maintains internal models of its environment to interpret sensory inputs and to prepare actions. Although behavioral studies have demonstrated that these internal models are optimally adapted to the statistics of the environment, the neural underpinning of this adaptation is unknown. Using a Bayesian model of sensory cortical processing, we related stimulus-evoked and spontaneous neural activities to inferences and prior expectations in an internal model and predicted that they should match if the model is statistically optimal. To test this prediction, we analyzed visual cortical activity of awake ferrets during development. Similarity between spontaneous and evoked activities increased with age and was specific to responses evoked by natural scenes. This demonstrates the progressive adaptation of internal models to the statistics of natural stimuli at the neural level.

Effective holographic theory of charge density waves

NASA Astrophysics Data System (ADS)

Amoretti, Andrea; Areán, Daniel; Goutéraux, Blaise; Musso, Daniele

2018-04-01

We use gauge/gravity duality to write down an effective low energy holographic theory of charge density waves. We consider a simple gravity model which breaks translations spontaneously in the dual field theory in a homogeneous manner, capturing the low energy dynamics of phonons coupled to conserved currents. We first focus on the leading two-derivative action, which leads to excited states with nonzero strain. We show that including subleading quartic derivative terms leads to dynamical instabilities of AdS2 translation invariant states and to stable phases breaking translations spontaneously. We compute analytically the real part of the electric conductivity. The model allows to construct Lifshitz-like hyperscaling violating quantum critical ground states breaking translations spontaneously. At these critical points, the real part of the dc conductivity can be metallic or insulating.

Learning by observing: the effect of multiple sessions of action-observation training on the spontaneous movement tempo and motor resonance.

PubMed

Lagravinese, Giovanna; Bisio, Ambra; Ruggeri, Piero; Bove, Marco; Avanzino, Laura

2017-02-01

The present study was designed to explore the changes in motor performance and motor resonance after multiple sessions of action observation (AO) training. Subjects were exposed to the observation of a video showing finger tapping movements executed at 3Hz, a frequency higher than the spontaneous one (2Hz) for four consecutive days. Motor performance and motor resonance were tested before the AO training on the first day, and on the last day. Results showed that multiple sessions of AO training induced a shift of the speed of execution of finger tapping movements toward the observed one and a change in motor resonance. Before the 3Hz-AO training cortical excitability was highest during the observation of the 2Hz video. This motor resonance effect was lost after one single session of 3Hz-AO training whereas after multiple sessions of 3Hz-AO training cortical excitability was highest during the observation of the 3Hz video. Our study shows for the first time that multiple sessions of AO training are able not only to induce performance gains but also to change the way by which the observer's motor system recognizes a certain movement as belonging to the individual motor repertoire. These results may encourage the development of novel rehabilitative protocols based on multiple sessions of action observation aimed to regain a correct movement when its spontaneous speed is modified by pathologies or to modify the innate temporal properties of certain movements. Copyright © 2017. Published by Elsevier Ltd.

On Dramatic Instruction: Towards a Taxonomy of Methods.

ERIC Educational Resources Information Center

Courtney, Richard

1987-01-01

Examines the many possible methods used by instructors who work with dramatic action: in educational drama, drama therapy, social drama, and theater. Discusses an emergent taxonomy whereby instructors choose either spontaneous/formal, overt/covert/, or intrinsic/extrinsic methods. (JC)

Subtype-specific differentiation of cardiac pacemaker cell clusters from human induced pluripotent stem cells.

PubMed

Schweizer, Patrick A; Darche, Fabrice F; Ullrich, Nina D; Geschwill, Pascal; Greber, Boris; Rivinius, Rasmus; Seyler, Claudia; Müller-Decker, Karin; Draguhn, Andreas; Utikal, Jochen; Koenen, Michael; Katus, Hugo A; Thomas, Dierk

2017-10-16

Human induced pluripotent stem cells (hiPSC) harbor the potential to differentiate into diverse cardiac cell types. Previous experimental efforts were primarily directed at the generation of hiPSC-derived cells with ventricular cardiomyocyte characteristics. Aiming at a straightforward approach for pacemaker cell modeling and replacement, we sought to selectively differentiate cells with nodal-type properties. hiPSC were differentiated into spontaneously beating clusters by co-culturing with visceral endoderm-like cells in a serum-free medium. Subsequent culturing in a specified fetal bovine serum (FBS)-enriched cell medium produced a pacemaker-type phenotype that was studied in detail using quantitative real-time polymerase chain reaction (qRT-PCR), immunocytochemistry, and patch-clamp electrophysiology. Further investigations comprised pharmacological stimulations and co-culturing with neonatal cardiomyocytes. hiPSC co-cultured in a serum-free medium with the visceral endoderm-like cell line END-2 produced spontaneously beating clusters after 10-12 days of culture. The pacemaker-specific genes HCN4, TBX3, and TBX18 were abundantly expressed at this early developmental stage, while levels of sarcomeric gene products remained low. We observed that working-type cardiomyogenic differentiation can be suppressed by transfer of early clusters into a FBS-enriched cell medium immediately after beating onset. After 6 weeks under these conditions, sinoatrial node (SAN) hallmark genes remained at high levels, while working-type myocardial transcripts (NKX2.5, TBX5) were low. Clusters were characterized by regular activity and robust beating rates (70-90 beats/min) and were triggered by spontaneous Ca 2+ transients recapitulating calcium clock properties of genuine pacemaker cells. They were responsive to adrenergic/cholinergic stimulation and able to pace neonatal rat ventricular myocytes in co-culture experiments. Action potential (AP) measurements of cells individualized from clusters exhibited nodal-type (63.4%) and atrial-type (36.6%) AP morphologies, while ventricular AP configurations were not observed. We provide a novel culture media-based, transgene-free approach for targeted generation of hiPSC-derived pacemaker-type cells that grow in clusters and offer the potential for disease modeling, drug testing, and individualized cell-based replacement therapy of the SAN.

Effects of platelet activating factor on contractile force and 45Ca fluxes in guinea-pig isolated atria.

PubMed Central

Diez, J.; Delpón, E.; Tamargo, J.

1990-01-01

1. The effects of platelet activating factor (PAF) were studied on the electromechanical properties and 45Ca2+ fluxes of guinea-pig isolated atria. 2 Both in spontaneously beating and electrically driven atria, PAF (10(-12)-10(-7) M) increased atrial rate but produced a biphasic effect on contractile force. At low concentrations (up to 10(-10) M) it produced a positive inotropic effect, while at higher concentrations PAF exerted a negative inotropic effect. A similar biphasic effect was observed in the slow contractions elicited by isoprenaline in K(+)-depolarized atrial fibres. 3. The positive inotropic effect of PAF was prevented by verapamil, whereas pretreatment of atria with propranolol, phentolamine, indomethacin or atropine did not modify its positive and negative inotropic actions. BN 52021, a specific PAF antagonist, abolished both the positive and negative inotropic effects. 4. PAF had no effect on the characteristics of the action potentials recorded in either normally polarized or K(+)-depolarized (slow action potential) atrial fibres. 5. At concentrations at which it increased contractile force, PAF potentiated the contractile responses to Ca2+ (0.9-9 mM), whereas at negative inotropic concentrations it inhibited them. The negative inotropic effect of PAF was partially reversed in 70% Na+ medium. 6. At 10(-11) M, PAF increased 45Ca2+ uptake and reduced the rate coefficient (kcm) for the 45Ca2+ efflux. This increase in 45Ca2+ uptake was abolished in atria pretreated with verapamil or BN 52021. However, 10(-7) M PAF modified neither 45Ca2+ uptake nor efflux in atrial muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2379035

Actions of (-)-baclofen on rat dorsal horn neurons.

PubMed

Kangrga, I; Jiang, M C; Randić, M

1991-10-25

The actions of a gamma-aminobutyric acid B (GABAB) agonist, (-)-baclofen, on the electrophysiological properties of neurons and synaptic transmission in the spinal dorsal horn (laminae I-IV) were examined by using intracellular recordings in spinal cord slice from young rats. In addition, the effects of baclofen on the dorsal root stimulation-evoked outflow of glutamate and aspartate from the spinal dorsal horn were examined by using high performance liquid chromatography (HPLC) with flourimetric detection. Superfusion of baclofen (5 nM to 10 microM) hyperpolarized, in a stereoselective and bicuculline-insensitive manner, the majority (86%) of tested neurons. The hyperpolarization was associated with a decrease in membrane resistance and persisted in a nominally zero-Ca2+, 10 mM Mg(2+)- or a TTX-containing solution. Our findings indicate that the hyperpolarizing effect of baclofen is probably due to an increase in conductance to potassium ions. Baclofen decreased the direct excitability of dorsal horn neurons, enhanced accommodation of spike discharge, and reduced the duration of Ca(2+)-dependent action potentials. Baclofen depressed, or blocked, excitatory postsynaptic potentials evoked by electrical stimulation of the dorsal roots. Spontaneously occurring synaptic potentials were also reversibly depressed by baclofen. Whereas baclofen did not produce any consistent change in the rate of the basal outflow of glutamate and aspartate, the stimulation-evoked release of the amino acids was blocked. The present results suggest that baclofen, by activating GABAB receptors, may modulate spinal afferent processing in the superficial dorsal horn by at least two mechanisms: (1) baclofen depresses excitatory synaptic transmission primarily by a presynaptic mechanism involving a decrease in the release of excitatory amino acids, and (2) at higher concentrations, the hyperpolarization and increased membrane conductance may contribute to the depressant effect of baclofen on excitatory synaptic transmission in the rat spinal dorsal horn.

AdE-1, a new inotropic Na(+) channel toxin from Aiptasia diaphana, is similar to, yet distinct from, known anemone Na(+) channel toxins.

PubMed

Nesher, Nir; Shapira, Eli; Sher, Daniel; Moran, Yehu; Tsveyer, Liora; Turchetti-Maia, Ana Luiza; Horowitz, Michal; Hochner, Binyamin; Zlotkin, Eliahu

2013-04-01

Heart failure is one of the most prevalent causes of death in the western world. Sea anemone contains a myriad of short peptide neurotoxins affecting many pharmacological targets, several of which possess cardiotonic activity. In the present study we describe the isolation and characterization of AdE-1 (ion channel modifier), a novel cardiotonic peptide from the sea anemone Aiptasia diaphana, which differs from other cnidarian toxins. Although AdE-1 has the same cysteine residue arrangement as sea anemone type 1 and 2 Na(+) channel toxins, its sequence contains many substitutions in conserved and essential sites and its overall homology to other toxins identified to date is low (<36%). Physiologically, AdE-1 increases the amplitude of cardiomyocyte contraction and slows the late phase of the twitch relaxation velocity with no induction of spontaneous twitching. It increases action potential duration of cardiomyocytes with no effect on its threshold and on the cell's resting potential. Similar to other sea anemone Na(+) channel toxins such as Av2 (Anemonia viridis toxin II), AdE-1 markedly inhibits Na(+) current inactivation with no significant effect on current activation, suggesting a similar mechanism of action. However, its effects on twitch relaxation velocity, action potential amplitude and on the time to peak suggest that this novel toxin affects cardiomyocyte function via a more complex mechanism. Additionally, Av2's characteristic delayed and early after-depolarizations were not observed. Despite its structural differences, AdE-1 physiologic effectiveness is comparable with Av2 with a similar ED(50) value to blowfly larvae. This finding raises questions regarding the extent of the universality of structure-function in sea anemone Na(+) channel toxins.

Patient-Specific Human Induced Pluripotent Stem Cell Model Assessed with Electrical Pacing Validates S107 as a Potential Therapeutic Agent for Catecholaminergic Polymorphic Ventricular Tachycardia

PubMed Central

Sasaki, Kenichi; Makiyama, Takeru; Yoshida, Yoshinori; Wuriyanghai, Yimin; Kamakura, Tsukasa; Nishiuchi, Suguru; Hayano, Mamoru; Harita, Takeshi; Yamamoto, Yuta; Kohjitani, Hirohiko; Hirose, Sayako; Chen, Jiarong; Kawamura, Mihoko; Ohno, Seiko; Itoh, Hideki; Takeuchi, Ayako; Matsuoka, Satoshi; Miura, Masaru; Sumitomo, Naokata; Horie, Minoru; Yamanaka, Shinya; Kimura, Takeshi

2016-01-01

Introduction Human induced pluripotent stem cells (hiPSCs) offer a unique opportunity for disease modeling. However, it is not invariably successful to recapitulate the disease phenotype because of the immaturity of hiPSC-derived cardiomyocytes (hiPSC-CMs). The purpose of this study was to establish and analyze iPSC-based model of catecholaminergic polymorphic ventricular tachycardia (CPVT), which is characterized by adrenergically mediated lethal arrhythmias, more precisely using electrical pacing that could promote the development of new pharmacotherapies. Method and Results We generated hiPSCs from a 37-year-old CPVT patient and differentiated them into cardiomyocytes. Under spontaneous beating conditions, no significant difference was found in the timing irregularity of spontaneous Ca2+ transients between control- and CPVT-hiPSC-CMs. Using Ca2+ imaging at 1 Hz electrical field stimulation, isoproterenol induced an abnormal diastolic Ca2+ increase more frequently in CPVT- than in control-hiPSC-CMs (control 12% vs. CPVT 43%, p<0.05). Action potential recordings of spontaneous beating hiPSC-CMs revealed no significant difference in the frequency of delayed afterdepolarizations (DADs) between control and CPVT cells. After isoproterenol application with pacing at 1 Hz, 87.5% of CPVT-hiPSC-CMs developed DADs, compared to 30% of control-hiPSC-CMs (p<0.05). Pre-incubation with 10 μM S107, which stabilizes the closed state of the ryanodine receptor 2, significantly decreased the percentage of CPVT-hiPSC-CMs presenting DADs to 25% (p<0.05). Conclusions We recapitulated the electrophysiological features of CPVT-derived hiPSC-CMs using electrical pacing. The development of DADs in the presence of isoproterenol was significantly suppressed by S107. Our model provides a promising platform to study disease mechanisms and screen drugs. PMID:27764147

Ethanol produces corticotropin releasing factor receptor-dependent enhancement of spontaneous glutamatergic transmission in the mouse central amygdala

PubMed Central

Silberman, Yuval; Fetterly, Tracy L.; Awad, Elias K.; Milano, Elana J.; Usdin, Ted B.; Winder, Danny G.

2015-01-01

Background Ethanol modulation of Central Amygdala (CeA) neurocircuitry plays a key role in the development of alcoholism via activation of the corticotropin releasing factor (CRF) receptor system. Previous work has predominantly focused on ethanol/CRF interactions on the CeA GABA circuitry; however our lab recently showed that CRF enhances CeA glutamatergic transmission. Therefore, this study sought to determine if ethanol modulates CeA glutamate transmission via activation of CRF signaling. Methods The effects of ethanol on spontaneous excitatory postsynaptic currents (sEPSCs) and basal resting membrane potentials were examined via standard electrophysiology methods in adult male C57BL/6J mice. Local ablation of CeA CRF neurons (CRFCeAhDTR) was achieved by targeting the human diphtheria toxin receptor (hDTR) to CeA CRF neurons with an adeno-associated virus. Ablation was quantified post-hoc with confocal microscopy. Genetic targeting of the diphtheria toxin active subunit to CRF neurons (CRFDTA mice) ablated CRF neurons throughout the CNS, as assessed by qRT-PCR quantification of CRF mRNA. Results Acute bath application of ethanol significantly increased sEPSC frequency in a concentration dependent manner in CeA neurons, and this effect was blocked by pretreatment of co-applied CRF receptor 1 and CRF receptor 2 antagonists. In experiments utilizing a CRF-tomato reporter mouse, ethanol did not significantly alter the basal membrane potential of CeA CRF neurons. The ability of ethanol to enhance CeA sEPSC frequency was not altered in CRFCeAhDTR mice despite a ~78% reduction in CeA CRF cell counts. The ability of ethanol to enhance CeA sEPSC frequency was also not altered in the CRFDTA mice despite a three-fold reduction in CRF mRNA levels. Conclusion These findings demonstrate that ethanol enhances spontaneous glutamatergic transmission in the CeA via a CRF receptor dependent mechanism. Surprisingly, our data suggest that this action may not require endogenous CRF. PMID:26503065

Upregulation of the sodium channel NaVβ4 subunit and its contributions to mechanical hypersensitivity and neuronal hyperexcitability in a rat model of radicular pain induced by local DRG inflammation

PubMed Central

Xie, Wenrui; Tan, Zhi-Yong; Barbosa, Cindy; Strong, Judith A.; Cummins, Theodore R.; Zhang, Jun-Ming

2016-01-01

High frequency spontaneous firing in myelinated sensory neurons plays a key role in initiating pain behaviors in several different models, including the radicular pain model in which the rat lumbar dorsal root ganglia (DRG) are locally inflamed. The sodium channel isoform NaV1.6 contributes to pain behaviors and spontaneous activity in this model. Among all the isoforms in adult DRG, NaV1.6 is the main carrier of TTX-sensitive resurgent Na currents that allow high-frequency firing. Resurgent currents flow after a depolarization or action potential, as a blocking particle exits the pore. In most neurons the regulatory β4 subunit is potentially the endogenous blocker. We used in vivo siRNA mediated knockdown of NaVβ4 to examine its role in the DRG inflammation model. NaVβ4 but not control siRNA almost completely blocked mechanical hypersensitivity induced by DRG inflammation. Microelectrode recordings in isolated whole DRGs showed that NaVβ4 siRNA blocked the inflammation-induced increase in spontaneous activity of Aβ neurons, and reduced repetitive firing and other measures of excitability. NaVβ4 was preferentially expressed in larger diameter cells; DRG inflammation increased its expression and this was reversed by NaVβ4 siRNA, based on immunohistochemistry and Western blotting. NaVβ4 siRNA also reduced immunohistochemical NaV1.6 expression. Patch clamp recordings of TTX-sensitive Na currents in acutely cultured medium diameter DRG neurons showed that DRG inflammation increased transient and especially resurgent current; effects blocked by NaVβ4 siRNA. NaVβ4 may represent a more specific target for pain conditions that depend on myelinated neurons expressing NaV1.6. PMID:26785322

Computer algorithms for automated detection and analysis of local Ca2+ releases in spontaneously beating cardiac pacemaker cells

PubMed Central

Kim, Mary S.; Tsutsui, Kenta; Stern, Michael D.; Lakatta, Edward G.; Maltsev, Victor A.

2017-01-01

Local Ca2+ Releases (LCRs) are crucial events involved in cardiac pacemaker cell function. However, specific algorithms for automatic LCR detection and analysis have not been developed in live, spontaneously beating pacemaker cells. In the present study we measured LCRs using a high-speed 2D-camera in spontaneously contracting sinoatrial (SA) node cells isolated from rabbit and guinea pig and developed a new algorithm capable of detecting and analyzing the LCRs spatially in two-dimensions, and in time. Our algorithm tracks points along the midline of the contracting cell. It uses these points as a coordinate system for affine transform, producing a transformed image series where the cell does not contract. Action potential-induced Ca2+ transients and LCRs were thereafter isolated from recording noise by applying a series of spatial filters. The LCR birth and death events were detected by a differential (frame-to-frame) sensitivity algorithm applied to each pixel (cell location). An LCR was detected when its signal changes sufficiently quickly within a sufficiently large area. The LCR is considered to have died when its amplitude decays substantially, or when it merges into the rising whole cell Ca2+ transient. Ultimately, our algorithm provides major LCR parameters such as period, signal mass, duration, and propagation path area. As the LCRs propagate within live cells, the algorithm identifies splitting and merging behaviors, indicating the importance of locally propagating Ca2+-induced-Ca2+-release for the fate of LCRs and for generating a powerful ensemble Ca2+ signal. Thus, our new computer algorithms eliminate motion artifacts and detect 2D local spatiotemporal events from recording noise and global signals. While the algorithms were developed to detect LCRs in sinoatrial nodal cells, they have the potential to be used in other applications in biophysics and cell physiology, for example, to detect Ca2+ wavelets (abortive waves), sparks and embers in muscle cells and Ca2+ puffs and syntillas in neurons. PMID:28683095

Slow Bursting Neurons of Mouse Cortical Layer 6b Are Depolarized by Hypocretin/Orexin and Major Transmitters of Arousal

PubMed Central

Wenger Combremont, Anne-Laure; Bayer, Laurence; Dupré, Anouk; Mühlethaler, Michel; Serafin, Mauro

2016-01-01

Neurons firing spontaneously in bursts in the absence of synaptic transmission have been previously recorded in different layers of cortical brain slices. It has been suggested that such neurons could contribute to the generation of alternating UP and DOWN states, a pattern of activity seen during slow-wave sleep. Here, we show that in layer 6b (L6b), known from our previous studies to contain neurons highly responsive to the wake-promoting transmitter hypocretin/orexin (hcrt/orx), there is a set of neurons, endowed with distinct intrinsic properties, which displayed a strong propensity to fire spontaneously in rhythmic bursts. In response to small depolarizing steps, they responded with a delayed firing of action potentials which, upon higher depolarizing steps, invariably inactivated and were followed by a depolarized plateau potential and a depolarizing afterpotential. These cells also displayed a strong hyperpolarization-activated rectification compatible with the presence of an Ih current. Most L6b neurons with such properties were able to fire spontaneously in bursts. Their bursting activity was of intrinsic origin as it persisted not only in presence of blockers of ionotropic glutamatergic and GABAergic receptors but also in a condition of complete synaptic blockade. However, a small number of these neurons displayed a mix of intrinsic bursting and synaptically driven recurrent UP and DOWN states. Most of the bursting L6b neurons were depolarized and excited by hcrt/orx through a direct postsynaptic mechanism that led to tonic firing and eventually inactivation. Similarly, they were directly excited by noradrenaline, histamine, dopamine, and neurotensin. Finally, the intracellular injection of these cells with dye and their subsequent Neurolucida reconstruction indicated that they were spiny non-pyramidal neurons. These results lead us to suggest that the propensity for slow rhythmic bursting of this set of L6b neurons could be directly impeded by hcrt/orx and other wake-promoting transmitters. PMID:27379007

Molecular expression and pharmacological evidence for a functional role of kv7 channel subtypes in Guinea pig urinary bladder smooth muscle.

PubMed

Afeli, Serge A Y; Malysz, John; Petkov, Georgi V

2013-01-01

Voltage-gated Kv7 (KCNQ) channels are emerging as essential regulators of smooth muscle excitability and contractility. However, their physiological role in detrusor smooth muscle (DSM) remains to be elucidated. Here, we explored the molecular expression and function of Kv7 channel subtypes in guinea pig DSM by RT-PCR, qRT-PCR, immunohistochemistry, electrophysiology, and isometric tension recordings. In whole DSM tissue, mRNAs for all Kv7 channel subtypes were detected in a rank order: Kv7.1~Kv7.2Kv7.3~Kv7.5Kv7.4. In contrast, freshly-isolated DSM cells showed mRNA expression of: Kv7.1~Kv7.2Kv7.5Kv7.3~Kv7.4. Immunohistochemical confocal microscopy analyses of DSM, conducted by using co-labeling of Kv7 channel subtype-specific antibodies and α-smooth muscle actin, detected protein expression for all Kv7 channel subtypes, except for the Kv7.4, in DSM cells. L-364373 (R-L3), a Kv7.1 channel activator, and retigabine, a Kv7.2-7.5 channel activator, inhibited spontaneous phasic contractions and the 10-Hz electrical field stimulation (EFS)-induced contractions of DSM isolated strips. Linopiridine and XE991, two pan-Kv7 (effective at Kv7.1-Kv7.5 subtypes) channel inhibitors, had opposite effects increasing DSM spontaneous phasic and 10 Hz EFS-induced contractions. EFS-induced DSM contractions generated by a wide range of stimulation frequencies were decreased by L-364373 (10 µM) or retigabine (10 µM), and increased by XE991 (10 µM). Retigabine (10 µM) induced hyperpolarization and inhibited spontaneous action potentials in freshly-isolated DSM cells. In summary, Kv7 channel subtypes are expressed at mRNA and protein levels in guinea pig DSM cells. Their pharmacological modulation can control DSM contractility and excitability; therefore, Kv7 channel subtypes provide potential novel therapeutic targets for urinary bladder dysfunction.

Caffeine tolerance: behavioral, electrophysiological and neurochemical evidence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chou, D.T.; Khan, S.; Forde, J.

The development of tolerance to the stimulatory action of caffeine upon mesencephalic reticular neurons and upon spontaneous locomotor activity was evaluated in rats after two weeks of chronic exposure to low doses of caffeine (5-10 mg/kg/day via their drinking water). These doses are achievable through dietary intake of caffeine-containing beverages in man. Concomitant measurement of (/sup 3/H)-CHA binding in the mesencephalic reticular formation was also carried out in order to explore the neurochemical basis of the development of tolerance. Caffeine, 2.5 mg/kg i.v., markedly increased the firing rate of reticular neurons in caffeine naive rats but failed to modify themore » neuronal activity in a group exposed chronically to low doses of caffeine. In addition, in spontaneous locomotor activity studies, the data show a distinct shift to the right of the caffeine dose-response curve in caffeine pretreated rats. These results clearly indicate that tolerance develops to the stimulatory action of caffeine upon the reticular formation at the single neuronal activity level as well as upon spontaneous locomotor activity. Furthermore, in chronically caffeine exposed rats, an increase in the number of binding sites for (/sup 3/H)-CHA was observed in reticular formation membranes without any change in receptor affinity. 28 references, 4 figures.« less

Neuropathic Pain-like Alterations in Muscle Nociceptor Function Associated with Vibration-induced Muscle Pain

PubMed Central

Chen, Xiaojie; Green, Paul G.; Levine, Jon D.

2010-01-01

We recently developed a rodent model of the painful muscle disorders induced by occupational exposure to vibration. In the present study we used this model to evaluate the function of sensory neurons innervating the vibration-exposed gastrocnemius muscle. Activity of 74 vibration-exposed and 40 control nociceptors, with mechanical receptive fields in the gastrocnemius muscle, were recorded. In vibration-exposed rats ~15% of nociceptors demonstrated an intense and long-lasting barrage of action potentials in response to sustained suprathreshold mechanical stimulation (average of 2635 action potentials with frequency of ~44 Hz during a 1 minute suprathreshold stimulus) much greater than has been reported to be produced even by potent inflammatory mediators. While these high-firing nociceptors had lower mechanical thresholds than the remaining nociceptors, exposure to vibration had no effect on conduction velocity and did not induce spontaneous activity. Hyperactivity was not observed in any of 19 neurons from vibration exposed rats pretreated with intrathecal antisense for the IL-6 receptor subunit gp130. Since vibration can injure peripheral nerves, and IL-6 has been implicated in painful peripheral neuropathies, we suggest that the dramatic change in sensory neuron function and development of muscles pain, induced by exposure to vibration, reflects a neuropathic muscle pain syndrome. PMID:20800357

Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells.

PubMed

Sirenko, Syevda G; Yang, Dongmei; Maltseva, Larissa A; Kim, Mary S; Lakatta, Edward G; Maltsev, Victor A

2017-01-01

Uptake and release calcium from the sarcoplasmic reticulum (SR) (dubbed "calcium clock"), in the form of spontaneous, rhythmic, local diastolic calcium releases (LCRs), together with voltage-sensitive ion channels (membrane clock) form a coupled system that regulates the action potential (AP) firing rate. LCRs activate Sodium/Calcium exchanger (NCX) that accelerates diastolic depolarization and thus participating in regulation of the time at which the next AP will occur. Previous studies in rabbit SA node cells (SANC) demonstrated that the basal AP cycle length (APCL) is tightly coupled to the basal LCR period (time from the prior AP-induced Ca2+ transient to the diastolic LCR occurrence), and that this coupling is further modulated by autonomic receptor stimulation. Although spontaneous LCRs during diastolic depolarization have been reported in SANC of various species (rabbit, cat, mouse, toad), prior studies have failed to detect LCRs in spontaneously beating SANC of guinea-pig, a species that has been traditionally used in studies of cardiac pacemaker cell function. We performed a detailed investigation of whether guinea-pig SANC generate LCRs and whether they play a similar key role in regulation of the AP firing rate. We used two different approaches, 2D high-speed camera and classical line-scan confocal imaging. Positioning the scan-line beneath sarcolemma, parallel to the long axis of the cell, we found that rhythmically beating guinea-pig SANC do, indeed, generate spontaneous, diastolic LCRs beneath the surface membrane. The average key LCR characteristics measured in confocal images in guinea-pig SANC were comparable to rabbit SANC, both in the basal state and in the presence of β-adrenergic receptor stimulation. Moreover, the relationship between the LCR period and APCL was subtended by the same linear function. Thus, LCRs in guinea-pig SANC contribute to the diastolic depolarization and APCL regulation. Our findings indicate that coupled-clock system regulation of APCL is a general, species-independent, mechanism of pacemaker cell normal automaticity. Lack of LCRs in prior studies is likely explained by technical issues, as individual LCRs are small stochastic events occurring mainly near the cell border.

Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells

PubMed Central

Sirenko, Syevda G.; Yang, Dongmei; Maltseva, Larissa A.; Kim, Mary S.; Lakatta, Edward G.

2017-01-01

Uptake and release calcium from the sarcoplasmic reticulum (SR) (dubbed “calcium clock”), in the form of spontaneous, rhythmic, local diastolic calcium releases (LCRs), together with voltage-sensitive ion channels (membrane clock) form a coupled system that regulates the action potential (AP) firing rate. LCRs activate Sodium/Calcium exchanger (NCX) that accelerates diastolic depolarization and thus participating in regulation of the time at which the next AP will occur. Previous studies in rabbit SA node cells (SANC) demonstrated that the basal AP cycle length (APCL) is tightly coupled to the basal LCR period (time from the prior AP-induced Ca2+ transient to the diastolic LCR occurrence), and that this coupling is further modulated by autonomic receptor stimulation. Although spontaneous LCRs during diastolic depolarization have been reported in SANC of various species (rabbit, cat, mouse, toad), prior studies have failed to detect LCRs in spontaneously beating SANC of guinea-pig, a species that has been traditionally used in studies of cardiac pacemaker cell function. We performed a detailed investigation of whether guinea-pig SANC generate LCRs and whether they play a similar key role in regulation of the AP firing rate. We used two different approaches, 2D high-speed camera and classical line-scan confocal imaging. Positioning the scan-line beneath sarcolemma, parallel to the long axis of the cell, we found that rhythmically beating guinea-pig SANC do, indeed, generate spontaneous, diastolic LCRs beneath the surface membrane. The average key LCR characteristics measured in confocal images in guinea-pig SANC were comparable to rabbit SANC, both in the basal state and in the presence of β-adrenergic receptor stimulation. Moreover, the relationship between the LCR period and APCL was subtended by the same linear function. Thus, LCRs in guinea-pig SANC contribute to the diastolic depolarization and APCL regulation. Our findings indicate that coupled-clock system regulation of APCL is a general, species-independent, mechanism of pacemaker cell normal automaticity. Lack of LCRs in prior studies is likely explained by technical issues, as individual LCRs are small stochastic events occurring mainly near the cell border. PMID:28945810

When do humans spontaneously adopt another's visuospatial perspective?

PubMed

Freundlieb, Martin; Kovács, Ágnes M; Sebanz, Natalie

2016-03-01

Perspective-taking is a key component of social interactions. However, there is an ongoing controversy about whether, when and how instances of spontaneous visuospatial perspective-taking occur. The aim of this study was to investigate the underlying factors as well as boundary conditions that characterize the spontaneous adoption of another person's visuospatial perspective (VSP) during social interactions. We used a novel paradigm, in which a participant and a confederate performed a simple stimulus-response (SR) compatibility task sitting at a 90° angle to each other. In this set-up, participants would show a spatial compatibility effect only if they adopted the confederate's VSP. In a series of 5 experiments we found that participants reliably adopted the VSP of the confederate, as long as he was perceived as an intentionally acting agent. Our results therefore show that humans are able to spontaneously adopt the differing VSP of another agent and that there is a tight link between perspective-taking and performing actions together. The results suggest that spontaneous VSP-taking can effectively facilitate and speed up spatial alignment processes accruing from dynamic interactions in multiagent environments. (c) 2016 APA, all rights reserved).

Consequences of metabolic inhibition in smooth muscle isolated from guinea-pig stomach.

PubMed

Nakayama, S; Chihara, S; Clark, J F; Huang, S M; Horiuchi, T; Tomita, T

1997-11-15

1. In smooth muscle isolated from the guinea-pig stomach, cyanide (CN) and iodoacetic acid (IAA) were applied to block oxidative phosphorylation and glycolysis, respectively. Effects of IAA on generation of spontaneous mechanical and electrical activities were systematically investigated by comparing those of CN. Spontaneous activity ceased in 10-20 min during applications of 1 mM IAA. On the other hand, application of 1 mM CN also reduced the spontaneous activity, but never terminated it. In the presence of CN the negativity of the resting membrane potential was slightly reduced. 2. When spontaneous activity ceased with IAA, the resting membrane potential was not significantly affected. Also, before ceasing, the amplitude and duration of the spontaneous electrical activity were significantly reduced. The amplitude of the electrotonic potential was, however, not changed by IAA. Further, glibenclamide did not prevent the effects of IAA. These results suggest that, unlike cardiac muscle, activation of metabolism-dependent K+ channels in stomach smooth muscle does not seem to play a major role in reducing and terminating spontaneous activity during metabolic inhibition. 3. Carbachol-induced contraction transiently increased, and subsequently decreased gradually during application of IAA. 4. After 50 min application of IAA, when there was no spontaneous activity, the concentrations of phosphocreatine (PCr) and ATP measured with 31P nuclear magnetic resonance decreased to 60 and 80% of the control, respectively, while inorganic phosphate (Pi) concentration paradoxically fell to below detectable levels. During subsequent prolonged application of IAA, high-energy phosphates steadily decreased. On the other hand, after 50 min CN application, [PCr] and [ATP] decreased to approximately 30 and 80% of the control, respectively, while [Pi] increased by 2.6-fold. 5. In the presence of either CN or IAA, spontaneous mechanical and electrical activities were reduced or eliminated, although amounts of high-energy phosphates sufficient to contract smooth muscle remained. It can be postulated that some mechanism(s) related to energy metabolism, but not including ATP-sensitive K+ channels, plays an important role in generating spontaneous activity in guinea-pig stomach smooth muscle. During metabolic inhibition the energy metabolism-dependent mechanism(s) would preserve high-energy phosphates, and consequently cell viability, by stopping spontaneous activity.

Magnetic noise as the cause of the spontaneous magnetization reversal of RE–TM–B permanent magnets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dmitriev, A. I., E-mail: aid@icp.ac.ru; Talantsev, A. D., E-mail: artgtx32@mail.ru; Kunitsyna, E. I.

2016-08-15

The relation between the macroscopic spontaneous magnetization reversal (magnetic viscosity) of (NdDySm)(FeCo)B alloys and the spectral characteristics of magnetic noise, which is caused by the random microscopic processes of thermally activated domain wall motion in a potential landscape with uniformly distributed potential barrier heights, is found.

Both neurons and astrocytes exhibited tetrodotoxin-resistant metabotropic glutamate receptor-dependent spontaneous slow Ca2+ oscillations in striatum.

PubMed

Tamura, Atsushi; Yamada, Naohiro; Yaguchi, Yuichi; Machida, Yoshio; Mori, Issei; Osanai, Makoto

2014-01-01

The striatum plays an important role in linking cortical activity to basal ganglia outputs. Group I metabotropic glutamate receptors (mGluRs) are densely expressed in the medium spiny projection neurons and may be a therapeutic target for Parkinson's disease. The group I mGluRs are known to modulate the intracellular Ca(2+) signaling. To characterize Ca(2+) signaling in striatal cells, spontaneous cytoplasmic Ca(2+) transients were examined in acute slice preparations from transgenic mice expressing green fluorescent protein (GFP) in the astrocytes. In both the GFP-negative cells (putative-neurons) and astrocytes of the striatum, spontaneous slow and long-lasting intracellular Ca(2+) transients (referred to as slow Ca(2+) oscillations), which lasted up to approximately 200 s, were found. Neither the inhibition of action potentials nor ionotropic glutamate receptors blocked the slow Ca(2+) oscillation. Depletion of the intracellular Ca(2+) store and the blockade of inositol 1,4,5-trisphosphate receptors greatly reduced the transient rate of the slow Ca(2+) oscillation, and the application of an antagonist against mGluR5 also blocked the slow Ca(2+) oscillation in both putative-neurons and astrocytes. Thus, the mGluR5-inositol 1,4,5-trisphosphate signal cascade is the primary contributor to the slow Ca(2+) oscillation in both putative-neurons and astrocytes. The slow Ca(2+) oscillation features multicellular synchrony, and both putative-neurons and astrocytes participate in the synchronous activity. Therefore, the mGluR5-dependent slow Ca(2+) oscillation may involve in the neuron-glia interaction in the striatum.

Intelligent flight control systems

NASA Technical Reports Server (NTRS)

Stengel, Robert F.

1993-01-01

The capabilities of flight control systems can be enhanced by designing them to emulate functions of natural intelligence. Intelligent control functions fall in three categories. Declarative actions involve decision-making, providing models for system monitoring, goal planning, and system/scenario identification. Procedural actions concern skilled behavior and have parallels in guidance, navigation, and adaptation. Reflexive actions are spontaneous, inner-loop responses for control and estimation. Intelligent flight control systems learn knowledge of the aircraft and its mission and adapt to changes in the flight environment. Cognitive models form an efficient basis for integrating 'outer-loop/inner-loop' control functions and for developing robust parallel-processing algorithms.

Reduced spontaneous but relatively normal deliberate vicarious representations in psychopathy

PubMed Central

Meffert, Harma; Gazzola, Valeria; den Boer, Johan A.; Bartels, Arnold A. J.

2013-01-01

Psychopathy is a personality disorder associated with a profound lack of empathy. Neuroscientists have associated empathy and its interindividual variation with how strongly participants activate brain regions involved in their own actions, emotions and sensations while viewing those of others. Here we compared brain activity of 18 psychopathic offenders with 26 control subjects while viewing video clips of emotional hand interactions and while experiencing similar interactions. Brain regions involved in experiencing these interactions were not spontaneously activated as strongly in the patient group while viewing the video clips. However, this group difference was markedly reduced when we specifically instructed participants to feel with the actors in the videos. Our results suggest that psychopathy is not a simple incapacity for vicarious activations but rather reduced spontaneous vicarious activations co-existing with relatively normal deliberate counterparts. PMID:23884812

Neurosteroid modulation of neuronal excitability and synaptic transmission in the rat medial vestibular nuclei.

PubMed

Grassi, Silvarosa; Frondaroli, Adele; Dieni, Cristina; Dutia, Mayank B; Pettorossi, Vito E

2007-07-01

In rat brainstem slices, we investigated the influence of the neurosteroids tetrahydrodeoxycorticosterone (THDOC) and allopregnanolone (ALLO) on the synaptically driven and spontaneous activity of vestibular neurons, by analysing their effects on the amplitude of the field potentials evoked in the medial vestibular nuclei (MVN) by vestibular afferent stimulation and on the spontaneous firing rate of MVN neurons. Furthermore, the interaction with gamma-aminobutyric acid (GABA) and glutamate receptors was analysed by using specific antagonists for GABA(A) (bicuculline), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/ kainate [2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(f)quinoxaline-7-sulphonamide disodium salt (NBQX)], N-methyl-D-aspartate (NMDA) [D-(-)-2-amino-5-phosphonopentanoic acid (AP-5)] and group I metabotropic glutamate receptors (mGlu-I) [(R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA)] receptors. THDOC and ALLO evoked two opposite long-lasting effects, consisting of either a potentiation or a reduction of field potential and firing rate, which showed early and late components, occurring in conjunction or separately after neurosteroid application. The depressions depended on GABA(A) receptors, as they were abolished by bicuculline, while early potentiation involved glutamate AMPA/kainate receptors, as NBQX markedly reduced the incidence of early firing rate enhancement and, in the case of ALLO, even provoked depression. This suggests that THDOC and ALLO enhance the GABA(A) inhibitory influence on the MVN neurons and facilitate the AMPA/kainate facilitatory one. Conversely, a late potentiation effect, which was still induced after glutamate and GABA(A) receptor blockade, might involve a different mechanism. We conclude that the modulation of neuronal activity in the MVN by THDOC and ALLO, through their actions on GABA(A) and AMPA/kainate receptors, may have a physiological role in regulating the vestibular system function under normal conditions and during the stress response that accompanies many forms of vestibular dysfunction.

Ultrafast optical transistor and router of multi-order fluorescence and spontaneous parametric four-wave mixing in Pr³⁺:YSO.

PubMed

Wen, Feng; Ali, Imran; Hasan, Abdulkhaleq; Li, Changbiao; Tang, Haijun; Zhang, Yufei; Zhang, Yanpeng

2015-10-15

We study the realization of an optical transistor (switch and amplifier) and router in multi-order fluorescence (FL) and spontaneous parametric four-wave mixing (SP-FWM). We estimate that the switching speed is about 15 ns. The router action results from the Autler-Townes splitting in spectral or time domain. The switch and amplifier are realized by dressing suppression and enhancement in FL and SP-FWM. The optical transistor and router can be controlled by multi-parameters (i.e., power, detuning, or polarization).

Self-cleaning of superhydrophobic surfaces by spontaneously jumping condensate drops

NASA Astrophysics Data System (ADS)

Wisdom, Katrina; Watson, Jolanta; Watson, Gregory; Chen, Chuan-Hua

2012-11-01

The self-cleaning function of superhydrophobic surfaces is conventionally attributed to the removal of contaminating particles by impacting or rolling water droplets, which implies the action of external forces such as gravity. Here, we demonstrate a new self-cleaning mechanism, whereby condensate drops spontaneously jump upon coalescence on a superhydrophobic surface, and the merged drop self-propels away from the surface along with the contaminants. The jumping-condensate mechanism is shown to autonomously clean superhydrophobic cicada wings, where the contaminating particles cannot be removed by external wind flow. Our findings offer new insights for the development of self-cleaning materials.

Kv1.1 knock-in ataxic mice exhibit spontaneous myokymic activity exacerbated by fatigue, ischemia and low temperature

PubMed Central

Brunetti, Orazio; Imbrici, Paola; Botti, Fabio Massimo; Pettorossi, Vito Enrico; D'Adamo, Maria Cristina; Valentino, Mario; Zammit, Christian; Mora, Marina; Gibertini, Sara; Di Giovanni, Giuseppe; Muscat, Richard; Pessia, Mauro

2012-01-01

Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder characterized by myokymia and attacks of ataxic gait often precipitated by stress. Several genetic mutations have been identified in the Shaker-like K+ channel Kv1.1 (KCNA1) of EA1 individuals, including V408A, which result in remarkable channel dysfunction. By inserting the heterozygous V408A, mutation in one Kv1.1 allele, a mouse model of EA1 has been generated (Kv1.1V408A/+). Here, we investigated the neuromuscular transmission of Kv1.1V408A/+ ataxic mice and their susceptibility to physiologically relevant stressors. By using in vivo preparations of lateral gastrocnemius (LG) nerve–muscle from Kv1.1+/+ and Kv1.1V408A/+ mice, we show that the mutant animals exhibit spontaneous myokymic discharges consisting of repeated singlets, duplets or multiplets, despite motor nerve axotomy. Two-photon laser scanning microscopy from the motor nerve, ex vivo, revealed spontaneous Ca2 + signals that occurred abnormally only in preparations dissected from Kv1.1V408A/+ mice. Spontaneous bursting activity, as well as that evoked by sciatic nerve stimulation, was exacerbated by muscle fatigue, ischemia and low temperatures. These stressors also increased the amplitude of compound muscle action potential. Such abnormal neuromuscular transmission did not alter fiber type composition, neuromuscular junction and vascularization of LG muscle, analyzed by light and electron microscopy. Taken together these findings provide direct evidence that identifies the motor nerve as an important generator of myokymic activity, that dysfunction of Kv1.1 channels alters Ca2 + homeostasis in motor axons, and also strongly suggest that muscle fatigue contributes more than PNS fatigue to exacerbate the myokymia/neuromyotonia phenotype. More broadly, this study points out that juxtaparanodal K+ channels composed of Kv1.1 subunits exert an important role in dampening the excitability of motor nerve axons during fatigue or ischemic insult. PMID:22609489

Give spontaneity and self-discovery a chance in ASD: spontaneous peripheral limb variability as a proxy to evoke centrally driven intentional acts

PubMed Central

Torres, Elizabeth B.; Yanovich, Polina; Metaxas, Dimitris N.

2013-01-01

Autism can be conceived as an adaptive biological response to an early unexpected developmental change. Under such conceptualization one could think of emerging biological compensatory mechanisms with unique manifestations in each individual. Within a large group of affected people this would result in a highly heterogeneous spectral disorder where it would be difficult to tap into the hidden potentials of any given individual. A pressing question is how to treat the disorder while harnessing the capabilities and predispositions that the individual has already developed. It would indeed be ideal to use such strengths to accelerate the learning of self-sufficiency and independence, important as the person transitions into adulthood. In this report, we introduce a new concept for therapeutic interventions and basic research in autism. We use visuo-spatial and auditory stimuli to help augment the physical reality of the child and sensory-substitute corrupted kinesthetic information quantified in his/her movement patterns to help the person develop volitional control over the hand motions. We develop a co-adaptive child-computer interface that closes the sensory-motor feedback loops by alerting the child of a cause-effect relationship between the statistics of his/her real-time hand movement patterns and those of external media states. By co-adapting the statistics of the media states and those of the child's real-time hand movements, we found that without any food/token reward the children naturally remained engaged in the task. Even in the absence of practice, the learning gains were retained, transferred and improved 2–4 weeks later. This new concept demonstrates that individuals with autism do have spontaneous sensory-motor adaptive capabilities. When led to their self-discovery, these patterns of spontaneous behavioral variability (SBV) morph into more predictive and reliable intentional actions. These can unlock and enhance exploratory behavior and autonomy in the individual with autism spectrum disorders (ASD). PMID:23898243

Physiological roles of glucocorticoids during early embryonic development of the zebrafish (Danio rerio)

PubMed Central

Wilson, K S; Matrone, G; Livingstone, D E W; Al-Dujaili, E A S; Mullins, J J; Tucker, C S; Hadoke, P W F; Kenyon, C J; Denvir, M A

2013-01-01

While glucocorticoids (GCs) are known to be present in the zebrafish embryo, little is known about their physiological roles at this stage. We hypothesised that GCs play key roles in stress response, hatching and swim activity during early development. To test this, whole embryo cortisol (WEC) and corticosteroid-related genes were measured in embryos from 6 to 120 h post fertilisation (hpf) by enzyme linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). Stress response was assessed by change in WEC following stirring, hypoxia or brief electrical impulses applied to the bathing water. The impact of pharmacological and molecular GC manipulation on the stress response, spontaneous hatching and swim activity at different stages of development was also assessed. WEC levels demonstrated a biphasic pattern during development with a decrease from 0 to 36 hpf followed by a progressive increase towards 120 hpf. This was accompanied by a significant and sustained increase in the expression of genes encoding cyp11b1 (GC biosynthesis), hsd11b2 (GC metabolism) and gr (GC receptor) from 48 to 120 hpf. Metyrapone (Met), an inhibitor of 11β-hydroxylase (encoded by cyp11b1), and cyp11b1 morpholino (Mo) knockdown significantly reduced basal and stress-induced WEC levels at 72 and 120 hpf but not at 24 hpf. Spontaneous hatching and swim activity were significantly affected by manipulation of GC action from approximately 48 hpf onwards. We have identified a number of key roles of GCs in zebrafish embryos contributing to adaptive physiological responses under adverse conditions. The ability to alter GC action in the zebrafish embryo also highlights its potential value for GC research. PMID:24167225

Calcium signaling properties of a thyrotroph cell line, mouse TαT1 cells.

PubMed

Tomić, Melanija; Bargi-Souza, Paula; Leiva-Salcedo, Elias; Nunes, Maria Tereza; Stojilkovic, Stanko S

2015-12-01

TαT1 cells are mouse thyrotroph cell line frequently used for studies on thyroid-stimulating hormone beta subunit gene expression and other cellular functions. Here we have characterized calcium-signaling pathways in TαT1 cells, an issue not previously addressed in these cells and incompletely described in native thyrotrophs. TαT1 cells are excitable and fire action potentials spontaneously and in response to application of thyrotropin-releasing hormone (TRH), the native hypothalamic agonist for thyrotrophs. Spontaneous electrical activity is coupled to small amplitude fluctuations in intracellular calcium, whereas TRH stimulates both calcium mobilization from intracellular pools and calcium influx. Non-receptor-mediated depletion of intracellular pool also leads to a prominent facilitation of calcium influx. Both receptor and non-receptor stimulated calcium influx is substantially attenuated but not completely abolished by inhibition of voltage-gated calcium channels, suggesting that depletion of intracellular calcium pool in these cells provides a signal for both voltage-independent and -dependent calcium influx, the latter by facilitating the pacemaking activity. These cells also express purinergic P2Y1 receptors and their activation by extracellular ATP mimics TRH action on calcium mobilization and influx. The thyroid hormone triiodothyronine prolongs duration of TRH-induced calcium spikes during 30-min exposure. These data indicate that TαT1 cells are capable of responding to natively feed-forward TRH signaling and intrapituitary ATP signaling with acute calcium mobilization and sustained calcium influx. Amplification of TRH-induced calcium signaling by triiodothyronine further suggests the existence of a pathway for positive feedback effects of thyroid hormones probably in a non-genomic manner. Published by Elsevier Ltd.

Hypocretin-2 (orexin-B) modulation of superficial dorsal horn activity in rat

PubMed Central

Grudt, Timothy J; van den Pol, Anthony N; Perl, Edward R

2002-01-01

The hypothalamic peptides hypocretin-1 (orexin A) and hypocretin-2 (Hcrt-2; orexin B) are important in modulating behaviours demanding arousal, including sleep and appetite. Fibres containing hypocretin project from the hypothalamus to the superficial dorsal horn (SDH) of the spinal cord (laminae I and II); however, the effects produced by hypocretins on SDH neurones are unknown. To study the action of Hcrt-2 on individual SDH neurones, tight-seal, whole-cell recordings were made with biocytin-filled electrodes from rat lumbar spinal cord slices. In 19 of 63 neurones, Hcrt-2 (30 nm to 1 μm) evoked an inward (excitatory) current accompanied by an increase in baseline noise. The inward current and noise were unaffected by TTX but were blocked by the P2X purinergic receptor antagonist suramin (300–500 μm). Hcrt-2 (30 nm to 1 μm) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in the majority of neurones. The sIPSC increase was blocked by strychnine (1 μm) and by TTX (1 μm), suggesting that the increased sIPSC frequency was glycine and action potential dependent. Hcrt-2 increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in a few neurones but had no effect on dorsal root-evoked EPSCs in these or in other neurones. Neurones located in outer lamina II, particularly radial and vertical cells, were most likely to respond to Hcrt-2. We conclude that Hcrt-2 has excitatory effects on certain SDH neurones, some of which exert inhibitory influences on other cells of the region, consistent with the perspective that hypocretin has a role in orchestrating reactions related to arousal, including nociception, pain and temperature sense. PMID:11790816

The role of gamma-aminobutyric acid/glycinergic synaptic transmission in mediating bilirubin-induced hyperexcitation in developing auditory neurons.

PubMed

Yin, Xin-Lu; Liang, Min; Shi, Hai-Bo; Wang, Lu-Yang; Li, Chun-Yan; Yin, Shan-Kai

2016-01-05

Hyperbilirubinemia is a common clinical phenomenon observed in human newborns. A high level of bilirubin can result in severe jaundice and bilirubin encephalopathy. However, the cellular mechanisms underlying bilirubin excitotoxicity are unclear. Our previous studies showed the action of gamma-aminobutyric acid (GABA)/glycine switches from excitatory to inhibitory during development in the ventral cochlear nucleus (VCN), one of the most sensitive auditory nuclei to bilirubin toxicity. In the present study, we investigated the roles of GABAA/glycine receptors in the induction of bilirubin hyperexcitation in early developing neurons. Using the patch clamp technique, GABAA/glycine receptor-mediated spontaneous inhibitory synaptic currents (sIPSCs) were recorded from bushy and stellate cells in acute brainstem slices from young mice (postnatal day 2-6). Bilirubin significantly increased the frequency of sIPSCs, and this effect was prevented by pretreatments of slices with either fast or slow Ca(2+) chelators BAPTA-AM and EGTA-AM suggesting that bilirubin can increase the release of GABA/glycine via Ca(2+)-dependent mechanisms. Using cell-attached recording configuration, we found that antagonists of GABAA and glycine receptors strongly attenuated spontaneous spiking firings in P2-6 neurons but produced opposite effect in P15-19 neurons. Furthermore, these antagonists reversed bilirubin-evoked hyperexcitability in P2-6 neurons, indicating that excitatory action of GABA/glycinergic transmission specifically contribute to bilirubin-induced hyperexcitability in the early stage of development. Our results suggest that bilirubin-induced enhancement of presynaptic release GABA/Glycine via Ca(2+)-dependent mechanisms may play a critical role in mediating neuronal hyperexcitation associated with jaundice, implicating potential new strategies for predicting, preventing, and treating bilirubin neurotoxicity. Copyright © 2015. Published by Elsevier Ireland Ltd.

Neurological Principles and Rehabilitation of Action Disorders: Common Clinical Deficits

PubMed Central

Sathian, K.; Buxbaum, Laurel J.; Cohen, Leonardo G.; Krakauer, John W.; Lang, Catherine E.; Corbetta, Maurizio; Fitzpatrick, Susan M.

2014-01-01

In this paper we use the CAP principles to consider the impact of common clinical problems on action. We focus on three major syndromes: paresis, apraxia and ataxia. We also review mechanisms that could account for spontaneous recovery, using what is known about the best studied clinical dysfunction, paresis, and also ataxia. Together, this and the previous paper lay the groundwork for the third paper in this series, which reviews the relevant rehabilitative interventions. PMID:21613535

Calcium transient dynamics and the mechanisms of ventricular vulnerability to single premature electrical stimulation in Langendorff-perfused rabbit ventricles

PubMed Central

Hayashi, Hideki; Kamanu, Santosh Dora; Ono, Norihiko; Kawase, Ayaka; Chou, Chung-Chuan; Weiss, James N.; Karagueuzian, Hrayr S.; Lin, Shien-Fong; Chen, Peng-Sheng

2009-01-01

BACKGROUND Single strong premature electrical stimulation (S2) may induce figure-eight reentry. We hypothesize that Ca current-mediated slow-response action potentials (APs) play a key role in the propagation in the central common pathway (CCP) of the reentry. METHODS We simultaneously mapped optical membrane potential (Vm) and intracellular Ca (Cai) transients in isolated Langendorff-perfused rabbit ventricles. Baseline pacing (S1) and a cathodal S2 (40 – 80 mA) were given at different epicardial sites with a coupling interval of 135 ± 20 ms. RESULTS In all 6 hearts, S2 induced graded responses around the S2 site. These graded responses propagated locally toward the S1 site and initiated fast APs from recovered tissues. The wavefront then circled around the refractory tissue near the site of S2. At the side of S2 opposite to the S1, the graded responses prolonged AP duration while the Cai continued to decline, resulting in a Cai sinkhole (an area of low Cai). The Cai in the sinkhole then spontaneously increased, followed by a slow Vm depolarization with a take-off potential of −40 ± 3.9 mV, which was confirmed with microelectrode recordings in 3 hearts. These slow-response APs then propagated through CCP to complete a figure-eight reentry. CONCLUSION We conclude that a strong premature stimulus can induce a Cai sinkhole at the entrance of the CCP. Spontaneous Cai elevation in the Cai sinkhole precedes the Vm depolarization, leading to Ca current-mediated slow propagation in the CCP. The slow propagation allows more time for tissues at the other side of CCP to recover and be excited to complete figure-eight reentry. PMID:18180025

Calcium transient dynamics and the mechanisms of ventricular vulnerability to single premature electrical stimulation in Langendorff-perfused rabbit ventricles.

PubMed

Hayashi, Hideki; Kamanu, Santosh Dora; Ono, Norihiko; Kawase, Ayaka; Chou, Chung-Chuan; Weiss, James N; Karagueuzian, Hrayr S; Lin, Shien-Fong; Chen, Peng-Sheng

2008-01-01

Single strong premature electrical stimulation (S(2)) may induce figure-eight reentry. We hypothesize that Ca current-mediated slow-response action potentials (APs) play a key role in the propagation in the central common pathway (CCP) of the reentry. We simultaneously mapped optical membrane potential (V(m)) and intracellular Ca (Ca(i)) transients in isolated Langendorff-perfused rabbit ventricles. Baseline pacing (S(1)) and a cathodal S(2) (40-80 mA) were given at different epicardial sites with a coupling interval of 135 +/- 20 ms. In all 6 hearts, S(2) induced graded responses around the S(2) site. These graded responses propagated locally toward the S(1) site and initiated fast APs from recovered tissues. The wavefront then circled around the refractory tissue near the site of S(2). At the side of S(2) opposite to the S(1), the graded responses prolonged AP duration while the Ca(i) continued to decline, resulting in a Ca(i) sinkhole (an area of low Ca(i)). The Ca(i) in the sinkhole then spontaneously increased, followed by a slow V(m) depolarization with a take-off potential of -40 +/- 3.9 mV, which was confirmed with microelectrode recordings in 3 hearts. These slow-response APs then propagated through CCP to complete a figure-eight reentry. We conclude that a strong premature stimulus can induce a Ca(i) sinkhole at the entrance of the CCP. Spontaneous Ca(i) elevation in the Ca(i) sinkhole precedes the V(m) depolarization, leading to Ca current-mediated slow propagation in the CCP. The slow propagation allows more time for tissues at the other side of CCP to recover and be excited to complete figure-eight reentry.

Damage to the ventromedial prefrontal cortex is associated with impairments in both spontaneous and deliberative moral judgments

PubMed Central

Cameron, C. Daryl; Reber, Justin; Spring, Victoria L.; Tranel, Daniel

2018-01-01

Implicit moral evaluations—spontaneous, unintentional judgments about the moral status of actions or persons—are thought to play a pivotal role in moral experience, suggesting a need for research to model these moral evaluations in clinical populations. Prior research reveals that the ventromedial prefrontal cortex (vmPFC) is a critical area underpinning affect and morality, and patients with vmPFC lesions show abnormalities in moral judgment and moral behavior. We use indirect measurement and multinomial modeling to understand differences in implicit moral evaluations among patients with vmPFC lesions. Our model quantifies multiple processes of moral judgment: implicit moral evaluations in response to distracting moral transgressions (Unintentional Judgment), accurate moral judgments about target actions (Intentional Judgment), and a directional tendency to judge actions as morally wrong (Response Bias). Compared to individuals with non-vmPFC brain damage and neurologically healthy comparisons, patients with vmPFC lesions showed a dual deficit in processes of moral judgment. First, patients with vmPFC lesions showed reduced Unintentional Judgment about moral transgressions, but not about non-moral negative affective distracters. Second, patients with vmPFC lesions showed reduced Intentional Judgment about target actions. These findings highlight the utility of a formal modeling approach in moral psychology, revealing a dual deficit in multiple component processes of moral judgment among patients with vmPFC lesions. PMID:29382558

Damage to the ventromedial prefrontal cortex is associated with impairments in both spontaneous and deliberative moral judgments.

PubMed

Cameron, C Daryl; Reber, Justin; Spring, Victoria L; Tranel, Daniel

2018-03-01

Implicit moral evaluations-spontaneous, unintentional judgments about the moral status of actions or persons-are thought to play a pivotal role in moral experience, suggesting a need for research to model these moral evaluations in clinical populations. Prior research reveals that the ventromedial prefrontal cortex (vmPFC) is a critical area underpinning affect and morality, and patients with vmPFC lesions show abnormalities in moral judgment and moral behavior. We use indirect measurement and multinomial modeling to understand differences in implicit moral evaluations among patients with vmPFC lesions. Our model quantifies multiple processes of moral judgment: implicit moral evaluations in response to distracting moral transgressions (Unintentional Judgment), accurate moral judgments about target actions (Intentional Judgment), and a directional tendency to judge actions as morally wrong (Response Bias). Compared to individuals with non-vmPFC brain damage and neurologically healthy comparisons, patients with vmPFC lesions showed a dual deficit in processes of moral judgment. First, patients with vmPFC lesions showed reduced Unintentional Judgment about moral transgressions, but not about non-moral negative affective distracters. Second, patients with vmPFC lesions showed reduced Intentional Judgment about target actions. These findings highlight the utility of a formal modeling approach in moral psychology, revealing a dual deficit in multiple component processes of moral judgment among patients with vmPFC lesions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Group Flow and Group Genius

ERIC Educational Resources Information Center

Sawyer, Keith

2015-01-01

Keith Sawyer views the spontaneous collaboration of group creativity and improvisation actions as "group flow," which organizations can use to function at optimum levels. Sawyer establishes ideal conditions for group flow: group goals, close listening, complete concentration, being in control, blending egos, equal participation, knowing…

PYRETHROID MODULATION OF SPONTANEOUS NEURONAL EXCITABILITY AND NEUROTRANSMISSION IN HIPPOCAMPAL NEURONS IN CULTURE

EPA Science Inventory

Pyrethroid insecticides have potent actions on voltage-gated sodium channels, inhibiting inactivation and increasing channel open times. These are thought to underlie, at least in part, the clinical symptoms of pyrethroid intoxication. However, disruption of neuronal activity at ...

[Cellular mechanism of the generation of spontaneous activity in gastric muscle].

PubMed

Nakamura, Eri; Kito, Yoshihiko; Fukuta, Hiroyasu; Yanai, Yoshimasa; Hashitani, Hikaru; Yamamoto, Yoshimichi; Suzuki, Hikaru

2004-03-01

In gastric smooth muscles, interstitial cells of Cajal (ICC) might be the pacemaker cells of spontaneous activities since ICC are rich in mitochondria and are connected with smooth muscle cells via gap junctions. Several types of ICC are distributed widely in the stomach wall. A group of ICC distributed in the myenteric layer (ICC-MY) were the pacemaker cells of gastrointestinal smooth muscles. Pacemaker potentials were generated in ICC-MY, and the potentials were conducted to circular smooth muscles to trigger slow waves and also conducted to longitudinal muscles to form follower potentials. In circular muscle preparations, interstitial cells distributed within muscle bundles (ICC-IM) produced unitary potentials, which were conducted to circular muscles to form slow potentials by summation. In mutant mice lacking inositol trisphosphate (IP(3)) receptor, slow waves were absent in gastric smooth muscles. The generation of spontaneous activity was impaired by the inhibition of Ca(2+)-release from internal stores through IP(3) receptors, inhibition of mitochondrial Ca(2+)-handling with proton pump inhibitors, and inhibition of ATP-sensitive K(+)-channels at the mitochondrial inner membrane. These results suggested that mitochondrial Ca(2+)-handling causes the generation of spontaneous activity in pacemaker cells. Possible involvement of protein kinase C (PKC) in the Ca(2+) signaling system was also suggested.

Antihypertensive effects of peroxisome proliferator-activated receptor-β/δ activation.

PubMed

Toral, Marta; Romero, Miguel; Pérez-Vizcaíno, Francisco; Duarte, Juan; Jiménez, Rosario

2017-02-01

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors, which is composed of three members encoded by distinct genes: PPARα, PPARβ/δ, and PPARγ. The biological actions of PPARα and PPARγ and their potential as a cardiovascular therapeutic target have been extensively reviewed, whereas the biological actions of PPARβ/δ and its effectiveness as a therapeutic target in the treatment of hypertension remain less investigated. Preclinical studies suggest that pharmacological PPARβ/δ activation induces antihypertensive effects in direct [spontaneously hypertensive rat (SHR), ANG II, and DOCA-salt] and indirect (dyslipemic and gestational) models of hypertension, associated with end-organ damage protection. This review summarizes mechanistic insights into the antihypertensive effects of PPARβ/δ activators, including molecular and functional mechanisms. Pharmacological PPARβ/δ activation induces genomic actions including the increase of regulators of G protein-coupled signaling (RGS), acute nongenomic vasodilator effects, as well as the ability to improve the endothelial dysfunction, reduce vascular inflammation, vasoconstrictor responses, and sympathetic outflow from central nervous system. Evidence from clinical trials is also examined. These preclinical and clinical outcomes of PPARβ/δ ligands may provide a basis for the development of therapies in combating hypertension. Copyright © 2017 the American Physiological Society.

The topography of generosity: asymmetric evaluations of prosocial actions.

PubMed

Klein, Nadav; Epley, Nicholas

2014-12-01

Prosociality is considered a virtue. Those who care for others are admired, whereas those who care only for themselves are despised. For one's reputation, it pays to be nice. Does it pay to be even nicer? Four experiments assess reputational inferences across the entire range of prosocial outcomes in zero-sum interactions, from completely selfish to completely selfless actions. We observed consistent nonlinear evaluations: Participants evaluated selfish actions more negatively than equitable actions, but they did not evaluate selfless actions markedly more favorably than equitable actions. This asymptotic pattern reflected monotonic evaluations for increasingly selfish actions and insensitivity to increasingly selfless actions. It pays to be nice but not to be really nice. Additional experiments suggest that this pattern stems partly from failing to make spontaneous comparisons between varying degrees of selflessness. We suggest that these reputational incentives could guide social norms, encouraging equitable actions but discouraging extremely selfless actions. PsycINFO Database Record (c) 2014 APA, all rights reserved.

N1 Magnitude of Auditory Evoked Potentials and Spontaneous Functional Connectivity Between Bilateral Heschl's Gyrus Are Coupled at Interindividual Level.

PubMed

Tan, Ao; Hu, Li; Tu, Yiheng; Chen, Rui; Hung, Yeung Sam; Zhang, Zhiguo

2016-07-01

N1 component of auditory evoked potentials is extensively used to investigate the propagation and processing of auditory inputs. However, the substantial interindividual variability of N1 could be a possible confounding factor when comparing different individuals or groups. Therefore, identifying the neuronal mechanism and origin of the interindividual variability of N1 is crucial in basic research and clinical applications. This study is aimed to use simultaneously recorded electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data to investigate the coupling between N1 and spontaneous functional connectivity (FC). EEG and fMRI data were simultaneously collected from a group of healthy individuals during a pure-tone listening task. Spontaneous FC was estimated from spontaneous blood oxygenation level-dependent (BOLD) signals that were isolated by regressing out task evoked BOLD signals from raw BOLD signals and then was correlated to N1 magnitude across individuals. It was observed that spontaneous FC between bilateral Heschl's gyrus was significantly and positively correlated with N1 magnitude across individuals (Spearman's R = 0.829, p < 0.001). The specificity of this observation was further confirmed by two whole-brain voxelwise analyses (voxel-mirrored homotopic connectivity analysis and seed-based connectivity analysis). These results enriched our understanding of the functional significance of the coupling between event-related brain responses and spontaneous brain connectivity, and hold the potential to increase the applicability of brain responses as a probe to the mechanism underlying pathophysiological conditions.

Spontaneous Swallowing Frequency [Has Potential to] Identify Dysphagia in Acute Stroke

PubMed Central

Carnaby, Giselle D; Sia, Isaac; Khanna, Anna; Waters, Michael

2014-01-01

Background and Purpose Spontaneous swallowing frequency has been described as an index of dysphagia in various health conditions. This study evaluated the potential of spontaneous swallow frequency analysis as a screening protocol for dysphagia in acute stroke. Methods In a cohort of 63 acute stroke cases swallow frequency rates (swallows per minute: SPM) were compared to stroke and swallow severity indices, age, time from stroke to assessment, and consciousness level. Mean differences in SPM were compared between patients with vs. without clinically significant dysphagia. ROC analysis was used to identify the optimal threshold in SPM which was compared to a validated clinical dysphagia examination for identification of dysphagia cases. Time series analysis was employed to identify the minimally adequate time period to complete spontaneous swallow frequency analysis. Results SPM correlated significantly with stroke and swallow severity indices but not with age, time from stroke onset, or consciousness level. Patients with dysphagia demonstrated significantly lower SPM rates. SPM differed by dysphagia severity. ROC analysis yielded a threshold of SPM ≤ 0.40 which identified dysphagia (per the criterion referent) with 0.96 sensitivity, 0.68 specificity, and 0.96 negative predictive value. Time series analysis indicated that a 5 to 10 minute sampling window was sufficient to calculate spontaneous swallow frequency to identify dysphagia cases in acute stroke. Conclusions Spontaneous swallowing frequency presents high potential to screen for dysphagia in acute stroke without the need for trained, available personnel. PMID:24149008

Spontaneous swallowing frequency has potential to identify dysphagia in acute stroke.

PubMed

Crary, Michael A; Carnaby, Giselle D; Sia, Isaac; Khanna, Anna; Waters, Michael F

2013-12-01

Spontaneous swallowing frequency has been described as an index of dysphagia in various health conditions. This study evaluated the potential of spontaneous swallow frequency analysis as a screening protocol for dysphagia in acute stroke. In a cohort of 63 acute stroke cases, swallow frequency rates (swallows per minute [SPM]) were compared with stroke and swallow severity indices, age, time from stroke to assessment, and consciousness level. Mean differences in SPM were compared between patients with versus without clinically significant dysphagia. Receiver operating characteristic curve analysis was used to identify the optimal threshold in SPM, which was compared with a validated clinical dysphagia examination for identification of dysphagia cases. Time series analysis was used to identify the minimally adequate time period to complete spontaneous swallow frequency analysis. SPM correlated significantly with stroke and swallow severity indices but not with age, time from stroke onset, or consciousness level. Patients with dysphagia demonstrated significantly lower SPM rates. SPM differed by dysphagia severity. Receiver operating characteristic curve analysis yielded a threshold of SPM≤0.40 that identified dysphagia (per the criterion referent) with 0.96 sensitivity, 0.68 specificity, and 0.96 negative predictive value. Time series analysis indicated that a 5- to 10-minute sampling window was sufficient to calculate spontaneous swallow frequency to identify dysphagia cases in acute stroke. Spontaneous swallowing frequency presents high potential to screen for dysphagia in acute stroke without the need for trained, available personnel.

A machine learning methodology for the selection and classification of spontaneous spinal cord dorsum potentials allows disclosure of structured (non-random) changes in neuronal connectivity induced by nociceptive stimulation

PubMed Central

Martin, Mario; Contreras-Hernández, Enrique; Béjar, Javier; Esposito, Gennaro; Chávez, Diógenes; Glusman, Silvio; Cortés, Ulises; Rudomin, Pablo

2015-01-01

Previous studies aimed to disclose the functional organization of the neuronal networks involved in the generation of the spontaneous cord dorsum potentials (CDPs) generated in the lumbosacral spinal segments used predetermined templates to select specific classes of spontaneous CDPs. Since this procedure was time consuming and required continuous supervision, it was limited to the analysis of two specific types of CDPs (negative CDPs and negative positive CDPs), thus excluding potentials that may reflect activation of other neuronal networks of presumed functional relevance. We now present a novel procedure based in machine learning that allows the efficient and unbiased selection of a variety of spontaneous CDPs with different shapes and amplitudes. The reliability and performance of the present method is evaluated by analyzing the effects on the probabilities of generation of different classes of spontaneous CDPs induced by the intradermic injection of small amounts of capsaicin in the anesthetized cat, a procedure known to induce a state of central sensitization leading to allodynia and hyperalgesia. The results obtained with the selection method presently described allowed detection of spontaneous CDPs with specific shapes and amplitudes that are assumed to represent the activation of functionally coupled sets of dorsal horn neurones that acquire different, structured configurations in response to nociceptive stimuli. These changes are considered as responses tending to adequate transmission of sensory information to specific functional requirements as part of homeostatic adjustments. PMID:26379540

Pairing-induced speedup of nuclear spontaneous fission

NASA Astrophysics Data System (ADS)

Sadhukhan, Jhilam; Dobaczewski, J.; Nazarewicz, W.; Sheikh, J. A.; Baran, A.

2014-12-01

Background: Collective inertia is strongly influenced at the level crossing at which the quantum system changes its microscopic configuration diabatically. Pairing correlations tend to make the large-amplitude nuclear collective motion more adiabatic by reducing the effect of these configuration changes. Competition between pairing and level crossing is thus expected to have a profound impact on spontaneous fission lifetimes. Purpose: To elucidate the role of nucleonic pairing on spontaneous fission, we study the dynamic fission trajectories of 264Fm and 240Pu using the state-of-the-art self-consistent framework. Methods: We employ the superfluid nuclear density functional theory with the Skyrme energy density functional SkM* and a density-dependent pairing interaction. Along with shape variables, proton and neutron pairing correlations are taken as collective coordinates. The collective inertia tensor is calculated within the nonperturbative cranking approximation. The fission paths are obtained by using the least action principle in a four-dimensional collective space of shape and pairing coordinates. Results: Pairing correlations are enhanced along the minimum-action fission path. For the symmetric fission of 264Fm, where the effect of triaxiality on the fission barrier is large, the geometry of the fission pathway in the space of the shape degrees of freedom is weakly impacted by pairing. This is not the case for 240Pu, where pairing fluctuations restore the axial symmetry of the dynamic fission trajectory. Conclusions: The minimum-action fission path is strongly impacted by nucleonic pairing. In some cases, the dynamical coupling between shape and pairing degrees of freedom can lead to a dramatic departure from the static picture. Consequently, in the dynamical description of nuclear fission, particle-particle correlations should be considered on the same footing as those associated with shape degrees of freedom.

Pairing-induced speedup of nuclear spontaneous fission

DOE PAGES

Sadhukhan, Jhilam; Dobaczewski, J.; Nazarewicz, W.; ...

2014-12-22

Collective inertia is strongly influenced at the level crossing at which the quantum system changes its microscopic configuration diabatically. Pairing correlations tend to make the large-amplitude nuclear collective motion more adiabatic by reducing the effect of these configuration changes. Competition between pairing and level crossing is thus expected to have a profound impact on spontaneous fission lifetimes. To elucidate the role of nucleonic pairing on spontaneous fission, we study the dynamic fission trajectories of 264Fm and 240Pu using the state-of-the-art self-consistent framework. We employ the superfluid nuclear density functional theory with the Skyrme energy density functional SkM* and a density-dependentmore » pairing interaction. Along with shape variables, proton and neutron pairing correlations are taken as collective coordinates. The collective inertia tensor is calculated within the nonperturbative cranking approximation. The fission paths are obtained by using the least action principle in a four-dimensional collective space of shape and pairing coordinates. Pairing correlations are enhanced along the minimum-action fission path. For the symmetric fission of 264Fm, where the effect of triaxiality on the fission barrier is large, the geometry of the fission pathway in the space of the shape degrees of freedom is weakly impacted by pairing. This is not the case for 240Pu, where pairing fluctuations restore the axial symmetry of the dynamic fission trajectory. The minimum-action fission path is strongly impacted by nucleonic pairing. In some cases, the dynamical coupling between shape and pairing degrees of freedom can lead to a dramatic departure from the static picture. As a result, in the dynamical description of nuclear fission, particle-particle correlations should be considered on the same footing as those associated with shape degrees of freedom.« less

Sodium channel slow inactivation as a therapeutic target for myotonia congenita

PubMed Central

Novak, Kevin R; Norman, Jennifer; Mitchell, Jacob R; Pinter, Martin J; Rich, Mark M

2014-01-01

Objective Patients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the chloride channel in skeletal muscle, which causes spontaneous firing of muscle action potentials (myotonia), producing muscle stiffness. In patients, muscle stiffness lessens with exercise, a change known as the warm-up phenomenon. Our goal was to identify the mechanism underlying warm up and to use this information to guide development of novel therapy. Methods To determine the mechanism underlying warm-up, we used a recently discovered drug to eliminate muscle contraction, thus allowing prolonged intracellular recording from individual muscle fibers during induction of warm-up in a mouse model of myotonia congenita. Results Changes in action potentials suggested slow inactivation of sodium channels as an important contributor to warm-up. These data suggested enhancing slow inactivation of sodium channels might offer effective therapy for myotonia. Lacosamide and ranolazine enhance slow inactivation of sodium channels and are FDA-approved for other uses in patients. We compared the efficacy of both drugs to mexiletine, a sodium channel blocker currently used to treat myotonia. In vitro studies suggested both lacosamide and ranolazine were superior to mexiletine. However, in vivo studies in a mouse model of myotonia congenita suggested side effects could limit the efficacy of lacosamide. Ranolazine produced fewer side effects and was as effective as mexiletine at a dose that produced none of mexiletine’s hypoexcitability side effects. Interpretation We conclude ranolazine has excellent therapeutic potential for treatment of patients with myotonia congenita. PMID:25515836

Characterization of the binding of 2-mercaptobenzimidazole to bovine serum albumin.

PubMed

Teng, Yue; Zou, Luyi; Huang, Ming; Zong, Wansong

2015-04-01

2-Mercaptobenzimidazole (MBI) is widely utilized as a corrosion inhibitor, copper-plating brightener and rubber accelerator. The residue of MBI in the environment is potentially harmful to human health. In this article, the interaction of MBI with bovine serum albumin (BSA) was explored using spectroscopic and molecular docking methods under physiological conditions. The positively charged MBI can spontaneously bind with the negatively charged BSA through electrostatic forces with one binding site. The site marker competition experiments and the molecular docking study revealed that MBI bound into site II (subdomain IIIA) of BSA, which further led to some secondary structure and microenvironmental changes of BSA. This work provides useful information on understanding the toxicological actions of MBI at the molecular level. Copyright © 2015 John Wiley & Sons, Ltd.

The brain in time: insights from neuromagnetic recordings.

PubMed

Hari, Riitta; Parkkonen, Lauri; Nangini, Cathy

2010-03-01

The millisecond time resolution of magnetoencephalography (MEG) is instrumental for investigating the brain basis of sensory processing, motor planning, cognition, and social interaction. We review the basic principles, recent progress, and future potential of MEG in noninvasive tracking of human brain activity. Cortical activation sequences from tens to hundreds of milliseconds can be followed during, e.g., perception, motor action, imitation, and language processing by recording both spontaneous and evoked brain signals. Moreover, tagging of sensory input can be used to reveal neuronal mechanisms of binaural interaction and perception of ambiguous images. The results support the emerging ideas of multiple, hierarchically organized temporal scales in human brain function. Instrumentation and data analysis methods are rapidly progressing, enabling attempts to decode the four-dimensional spatiotemporal signal patterns to reveal correlates of behavior and mental contents.

Understanding and improving photo-control of ion channels in nociceptors with azobenzene photo-switches.

PubMed

Mourot, Alexandre; Herold, Christian; Kienzler, Michael A; Kramer, Richard H

2017-06-20

The photo-isomerizable local anaesthetic, quaternary ammonium-azobenzene-quaternary ammonium (QAQ), provides rapid, optical control over pain signalling without involving genetic modification. In darkness or in green light, trans-QAQ blocks voltage-gated K + and Na + channels and silences action potentials in pain-sensing neurons. Upon photo-isomerization to cis with near UV light, QAQ blockade is rapidly relieved, restoring neuronal activity. However, the molecular mechanism of cis and trans QAQ blockade is not known. Moreover, the absorption spectrum of QAQ requires UV light for photo-control, precluding use deep inside neural tissue. Electrophysiology and molecular modelling were used to characterize the binding of cis and trans QAQ to voltage-gated K + channels and to develop quaternary ammonium-ethylamine-azobenzene-quaternary ammonium (QENAQ), a red-shifted QAQ derivative controlled with visible light. trans QAQ was sixfold more potent than cis QAQ, in blocking current through Shaker K + channels. Both isomers were use-dependent, open channel blockers, binding from the cytoplasmic side, but only trans QAQ block was slightly voltage dependent. QENAQ also blocked native K + and Na + channels preferentially in the trans state. QENAQ was photo-isomerized to cis with blue light and spontaneously reverted to trans within seconds in darkness, enabling rapid photo-control of action potentials in sensory neurons. Light-switchable local anaesthetics provide a means to non-invasively photo-control pain signalling with high selectivity and fast kinetics. Understanding the mode of action of QAQ and related compounds will help to design of drugs with improved photo-pharmacological properties. © 2017 The British Pharmacological Society.

Amphetamine Paradoxically Augments Exocytotic Dopamine Release and Phasic Dopamine Signals

PubMed Central

Daberkow, DP; Brown, HD; Bunner, KD; Kraniotis, SA; Doellman, MA; Ragozzino, ME; Garris, PA; Roitman, MF

2013-01-01

Drugs of abuse hijack brain reward circuitry during the addiction process by augmenting action potential-dependent phasic dopamine release events associated with learning and goal-directed behavior. One prominent exception to this notion would appear to be amphetamine (AMPH) and related analogs, which are proposed instead to disrupt normal patterns of dopamine neurotransmission by depleting vesicular stores and promoting non-exocytotic dopamine efflux via reverse transport. This mechanism of AMPH action, though, is inconsistent with its therapeutic effects and addictive properties - which are thought to be reliant on phasic dopamine signaling. Here we used fast-scan cyclic voltammetry in freely moving rats to interrogate principal neurochemical responses to AMPH in the striatum and relate these changes to behavior. First, we showed that AMPH dose-dependently enhanced evoked dopamine responses to phasic-like current pulse trains for up to two hours. Modeling the data revealed that AMPH inhibited dopamine uptake but also unexpectedly potentiated vesicular dopamine release. Second, we found that AMPH increased the amplitude, duration and frequency of spontaneous dopamine transients, the naturally occurring, non-electrically evoked, phasic increases in extracellular dopamine. Finally, using an operant sucrose reward paradigm, we showed that low-dose AMPH augmented dopamine transients elicited by sucrose-predictive cues. However, operant behavior failed at high-dose AMPH, which was due to phasic dopamine hyperactivity and the decoupling of dopamine transients from the reward predictive cue. These findings identify up-regulation of exocytotic dopamine release as a key AMPH action in behaving animals and support a unified mechanism of abused drugs to activate phasic dopamine signaling. PMID:23303926

The perception of rational, goal-directed action in nonhuman primates.

PubMed

Wood, Justin N; Glynn, David D; Phillips, Brenda C; Hauser, Marc D

2007-09-07

Humans are capable of making inferences about other individuals' intentions and goals by evaluating their actions in relation to the constraints imposed by the environment. This capacity enables humans to go beyond the surface appearance of behavior to draw inferences about an individual's mental states. Presently unclear is whether this capacity is uniquely human or is shared with other animals. We show that cotton-top tamarins, rhesus macaques, and chimpanzees all make spontaneous inferences about a human experimenter's goal by attending to the environmental constraints that guide rational action. These findings rule out simple associative accounts of action perception and show that our capacity to infer rational, goal-directed action likely arose at least as far back as the New World monkeys, some 40 million years ago.

Photocontrol of Voltage-Gated Ion Channel Activity by Azobenzene Trimethylammonium Bromide in Neonatal Rat Cardiomyocytes

PubMed Central

Frolova, Sheyda R.; Gaiko, Olga; Tsvelaya, Valeriya A.; Pimenov, Oleg Y.; Agladze, Konstantin I.

2016-01-01

The ability of azobenzene trimethylammonium bromide (azoTAB) to sensitize cardiac tissue excitability to light was recently reported. The dark, thermally relaxed trans- isomer of azoTAB suppressed spontaneous activity and excitation propagation speed, whereas the cis- isomer had no detectable effect on the electrical properties of cardiomyocyte monolayers. As the membrane potential of cardiac cells is mainly controlled by activity of voltage-gated ion channels, this study examined whether the sensitization effect of azoTAB was exerted primarily via the modulation of voltage-gated ion channel activity. The effects of trans- and cis- isomers of azoTAB on voltage-dependent sodium (INav), calcium (ICav), and potassium (IKv) currents in isolated neonatal rat cardiomyocytes were investigated using the whole-cell patch-clamp technique. The experiments showed that azoTAB modulated ion currents, causing suppression of sodium (Na+) and calcium (Ca2+) currents and potentiation of net potassium (K+) currents. This finding confirms that azoTAB-effect on cardiac tissue excitability do indeed result from modulation of voltage-gated ion channels responsible for action potential. PMID:27015602

Changes in intrinsic excitability of ganglion cells in degenerated retinas of RCS rats.

PubMed

Ren, Yi-Ming; Weng, Chuan-Huang; Zhao, Cong-Jian; Yin, Zheng-Qin

2018-01-01

To evaluate the intrinsic excitability of retinal ganglion cells (RGCs) in degenerated retinas. The intrinsic excitability of various morphologically defined RGC types using a combination of patch-clamp recording and the Lucifer yellow tracer in retinal whole-mount preparations harvested from Royal College of Surgeons (RCS) rats, a common retinitis pigmentosa (RP) model, in a relatively late stage of retinal degeneration (P90) were investigated. Several parameters of RGC morphologies and action potentials (APs) were measured and compared to those of non-dystrophic control rats, including dendritic stratification, dendritic field diameter, peak amplitude, half width, resting membrane potential, AP threshold, depolarization to threshold, and firing rates. Compared with non-dystrophic control RGCs, more depolarizations were required to reach the AP threshold in RCS RGCs with low spontaneous spike rates and in RCS OFF cells (especially A2o cells), and RCS RGCs maintained their dendritic morphologies, resting membrane potentials and capabilities to generate APs. RGCs are relatively well preserved morphologically and functionally, and some cells are more susceptible to decreased excitability during retinal degeneration. These findings provide valuable considerations for optimizing RP therapeutic strategies.

Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor.

PubMed

Duan, Xiaojie; Gao, Ruixuan; Xie, Ping; Cohen-Karni, Tzahi; Qing, Quan; Choe, Hwan Sung; Tian, Bozhi; Jiang, Xiaocheng; Lieber, Charles M

2011-12-18

The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally, the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and because their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously, we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here, we report a new approach in which a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be recorded, thus showing that a stable and tight seal forms between the nanotube and cell membrane. We also show that multiple BIT-FETs can record multiplexed intracellular signals from both single cells and networks of cells.

Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor

NASA Astrophysics Data System (ADS)

Duan, Xiaojie; Gao, Ruixuan; Xie, Ping; Cohen-Karni, Tzahi; Qing, Quan; Choe, Hwan Sung; Tian, Bozhi; Jiang, Xiaocheng; Lieber, Charles M.

2012-03-01

The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally, the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and because their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously, we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here, we report a new approach in which a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be recorded, thus showing that a stable and tight seal forms between the nanotube and cell membrane. We also show that multiple BIT-FETs can record multiplexed intracellular signals from both single cells and networks of cells.

Electrophysiological time course and brain areas of spontaneous and intentional trait inferences

PubMed Central

Van Duynslaeger, Marijke; Verstraeten, Edwin

2007-01-01

This study measured event-related potentials during spontaneous and intentional trait inferences. Participants read sentences describing the behavior of a target person from which a strong moral trait could be inferred. The last word of each sentence determined the consistency with the trait induced during an introductory paragraph. In comparison with behaviors that were consistent with the implied trait, a P300 waveform was obtained when the behaviors were evaluative inconsistent with that trait. This dependency on behavioral consistency indicates that trait inferences were made previously while reading the preceding behaviors, irrespective of the participants’ spontaneous or intentional goals. Overall, the P300 shows considerable parallels between spontaneous and intentional inferences, indicating that the type and timing of the inconsistency process is very similar. In contrast, source localization (LORETA) of the event-related potentials suggest that spontaneous inferences show greater activation in the temporo-parietal junction compared to intentional inferences following an inconsistency. Memory measures taken after the presentation of the stimulus material involved sentence completion and trait-cued recall, and supported the occurrence of trait inferences associated with the actor. They also showed significant correlations with the neural components (i.e. P300 and its current density at the temporo-parietal junction) predominantly following spontaneous instructions, indicating that these components are valid neural indices of spontaneous inferences. PMID:18985139

[Vitamin para-aminobenzoic acid inhibits development of SOS function in tif-1 mutants of Escherichia coli at nonpermissive temperatures].

PubMed

Vasil'eva, S V; Gorb, T E; Rapoport, I A

1983-12-01

The development of "SOS" inducible functions in lysogenic and non-lysogenic strains of Escherichia coli tif-1 sfiA11 (lambda) at nonpermissive temperature of 42 degrees C was strongly suppressed by para-aminobenzoic acid (PABA). The rate of prophage lambda induction decreased 400 times, as compared to the control level; the efficiency of W-reactivation of UV-irradiated phage lambda decreased 37.5 to 16%. PABA also inhibited to some extent (1.5 times) the process of inducible recombination on the RecF pathway. The processes of spontaneous lambda induction and W-reactivation, as well as spontaneous recombination on RecBC and RecF pathways, were not influenced by PABA. The above data are in accordance with previous studies of PABA action when the manifestation of "SOS" functions was induced by chemical mutagens. The action of PABA has been tentatively interpreted on the basis of negative control of "SOS" repair pathway.

Control technique of spontaneous combustion in fully mechan ized stope during period of end caving under complex mining influence

NASA Astrophysics Data System (ADS)

Yuan, Benqing

2018-01-01

In view of the phenomenon of spontaneous combustion of coal seam occurring during the period of end caving under complex mining conditions, taking the 1116 (3) stope of Guqiao mine as the object of study, the causes of spontaneous combustion during the period of end caving are analyzed, according to the specific geological conditions of the stope to develop corresponding fire prevention measures, including the reduction of air supply and air leakage in goaf, reduce the amount of coal left, reasonable drainage, nitrogen injection for spontaneous combustion prevention, grouting for spontaneous combustion prevention and permanent closure, fundamentally eliminates the potential for spontaneous combustion during the period of 1116(3) stope end caving. The engineering practice shows that this kind of measure has reference value for the prevention and control of spontaneous combustion during the period of stope end caving.

Effects of communication on the performance of nursing students during the simulation of an emergency situation.

PubMed

Chapelain, Pascal; Morineau, Thierry; Gautier, Claudie

2015-11-01

To explore how nursing performance is impacted by different forms of team communication including a message transmitted through an earpiece which triggers reflective thinking in the simulation of a deteriorating patient situation. Communication can either support team performance or produce interruptions potentially leading to error. Today, technology offers the opportunity to use devices that can permit communication. An experimental protocol was used with quantitative and qualitative analyses. Pairs of nursing students (N = 26) were dispatched to either an experimental group having to wear an earpiece priming reflective thinking, or to a control group. The study was conducted between October 2013-April 2014. The number of spontaneous information exchanges between pairs of participants was positively correlated with overall performance (actions performed and physician call) and with actions performed at the right moment. The number of questions in the team was positively correlated with overall action performance. No quantitative effect of the earpiece message on the performance indicators was found. But, a qualitative observation showed that this message can allow for error avoidance. Subjective evaluation of the earpiece as an aid was negatively correlated with overall action performance. Its evaluation as a disturbance was also negatively correlated with the measurement of actions performed at the right moment. The ability to exchange information and to ask questions seems to contribute to performance in care delivery. The use of communication devices to trigger reflective thinking must be studied in more depth to assess their capacity to improve performance. © 2015 John Wiley & Sons Ltd.

Experimental study of brachial plexus and vessel compression: evaluation of combined central and peripheral electrodiagnostic approach.

PubMed

Yang, Chaoqun; Xu, Jianguang; Chen, Jie; Li, Shulin; Cao, Yu; Zhu, Yi; Xu, Lei

2017-08-01

We sought to investigate the reliability of a new electrodiagnostic method for identifying Electrodiagnosis of Brachial Plexus & Vessel Compression Syndrome (BPVCS) in rats that involves the application of transcranial electrical stimulation motor evoked potentials (TES-MEPs) combined with peripheral nerve stimulation compound muscle action potentials (PNS-CMAPs). The latencies of the TES-MEP and PNS-CMAP were initially elongated in the 8-week group. The amplitudes of TES-MEP and PNS-CMAP were initially attenuated in the 16-week group. The isolateral amplitude ratio of the TES-MEP to the PNS-CMAP was apparently decreased, and spontaneous activities emerged at 16 weeks postoperatively. Superior and inferior trunk models of BPVCS were created in 72 male Sprague Dawley (SD) rats that were divided into six experimental groups. The latencies, amplitudes and isolateral amplitude ratios of the TES-MEPs and PNS-CMAPs were recorded at different postoperative intervals. Electrophysiological and histological examinations of the rats' compressed brachial plexus nerves were utilized to establish preliminary electrodiagnostic criteria for BPVCS.

The synaptic ribbon is critical for sound encoding at high rates and with temporal precision

PubMed Central

Chakrabarti, Rituparna; Picher, Maria Magdalena; Neef, Jakob; Jung, SangYong; Gültas, Mehmet; Maxeiner, Stephan

2018-01-01

We studied the role of the synaptic ribbon for sound encoding at the synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in mice lacking RIBEYE (RBEKO/KO). Electron and immunofluorescence microscopy revealed a lack of synaptic ribbons and an assembly of several small active zones (AZs) at each synaptic contact. Spontaneous and sound-evoked firing rates of SGNs and their compound action potential were reduced, indicating impaired transmission at ribbonless IHC-SGN synapses. The temporal precision of sound encoding was impaired and the recovery of SGN-firing from adaptation indicated slowed synaptic vesicle (SV) replenishment. Activation of Ca2+-channels was shifted to more depolarized potentials and exocytosis was reduced for weak depolarizations. Presynaptic Ca2+-signals showed a broader spread, compatible with the altered Ca2+-channel clustering observed by super-resolution immunofluorescence microscopy. We postulate that RIBEYE disruption is partially compensated by multi-AZ organization. The remaining synaptic deficit indicates ribbon function in SV-replenishment and Ca2+-channel regulation. PMID:29328020

Analysis and Chemistry of Novel Protein Oxidation Markers in Vivo.

PubMed

Henning, Christian; Liehr, Kristin; Girndt, Matthias; Ulrich, Christof; Glomb, Marcus A

2018-05-09

Proteins continually undergo spontaneous oxidation reactions, which lead to changes in structure and function. The quantitative assessment of protein oxidation adducts provides information on the level of exposure to reactive precursor compounds with a high oxidizing potential and reactive oxygen species (ROS). In the present work, we introduce N 6 -(2-hydroxyethyl)lysine as a novel marker based on the ratio of glycolaldehyde and its oxidized form glyoxal. The high analytical potential was proven with a first set of patients undergoing hemodialysis versus healthy controls, in comparison with well-established parameters for oxidative stress. In vitro experiments with N 1 - t-BOC-lysine and N 1 - t-BOC-arginine enlightened the mechanistic relationship of glycolaldehyde and glyoxal. Oxidation was strongly dependent on the catalytic action of the ε-amino moiety of lysine. Investigations on the formation of N 6 -carboxymethyl lysine revealed glycolaldehyde-imine as the more reactive precursor, even though an additional oxidative step is required. As a result, a novel and very effective alternative mechanism was unraveled.

Social Support Networks: An Underutilized Resource for the Prevention of HIV and other Sexually Transmitted Diseases among Hispanic/Latino Migrants and Immigrants.

PubMed

Painter, Thomas M

2018-01-01

Hispanic/Latino migrants and immigrants are vulnerable to infection by HIV and other sexually transmitted diseases (STDs). Participation in social support networks helps them cope with circumstances in the U.S. Studies of Hispanic/Latino migrants suggest that participation may also be protective against HIV/STD infection. However the studies do not satisfactorily explain how participation leads to protective actions, and recommend externally-induced interventions for HIV/STD prevention rather than incorporating the spontaneously occurring forms of social support they describe. Given the potential protective effects of support networks, a database search was conducted to ascertain the extent to which published HIV/STD prevention interventions for these populations incorporate their support networks. Very few interventions were identified and fewer still incorporate support networks. This commentary calls for research to understand more fully how support networks affect HIV/STD risks among Hispanic/Latino migrants and immigrants and identifies potential benefits of incorporating these networks in HIV/STD prevention for these vulnerable populations.

Sperm storage influences the potential for spontaneous acrosome reaction of the sperm in the newt Cynops pyrrhogaster.

PubMed

Kon, Shinnosuke; Sato, Tae; Endo, Daisuke; Takahashi, Tomoe; Takaku, Akio; Nakauchi, Yuni; Toyama, Fubito; Meyer-Rochow, Victor B; Takayama-Watanabe, Eriko; Watanabe, Akihiko

2017-12-01

Sperm storage is supposed to influence sperm quality, although the details remain unclear. In the present study, we found that sperm stored in a sperm storage site, the vas deferens of Cynops pyrrhogaster, spontaneously undergo acrosome reaction following incubation in Steinberg's salt solution (ST). Percentages of acrosome-reacted sperm increased time-dependently to about 60% in 24 hr. The concentration of cyclic adenosine monophosphate (cAMP) was elevated after incubating sperm in ST, while dibutylyl cAMP induced an acrosome reaction. Chelating of extracellular Ca 2+ suppressed the dibutylyl cAMP-induced acrosome reaction as well as spontaneous acrosome reaction in ST. These results suggest that cAMP elevation driven by Ca 2+ influx can be a cue for spontaneous acrosome reaction. Relatively low Ca 2+ concentration and pH in the vas deferens were sufficient to suppress spontaneous acrosome reaction within 1 hr. In addition, the cysteine rich secretory protein 2 gene was expressed in the vas deferens, indicating that it may be involved in the continuous suppression of spontaneous acrosome reaction. Sperm that underwent spontaneous acrosome reaction in ST was significantly increased when stored in the vas deferens for longer periods, or by males experiencing temperatures in excess of 12°C during hibernation conditions. Percentages of the spontaneously acrosome-reacted sperm were found to differ among males even though they were of identical genetic background. Taken together, C. pyrrhogaster sperm possess the potential for spontaneous acrosome reaction that does not become obvious in the vas deferens, unless promoted in correlation with sperm storage. © 2017 Wiley Periodicals, Inc.

[Antimutagenic activity of plant extracts from Armoracia rusticana, Ficus carica and Zea mays and peroxidase in eukaryotic cells].

PubMed

Agabeĭli, R A; Kasimova, T E; Alekperov, U K

2004-01-01

Antimutagene activity and high efficiency of antimutagene action of plant extracts from horseradish roots (Armoracia rusticana), fig brunches (Ficus carica) and mays seedlings (Zea mays) and their ability to decrease the frequency of spontaneous and induced by gamma-rays chromosome aberrations in meristematic cells of Vicia faba and marrow cells of mice have been shown. Comparative assessment of genoprotective properties of peroxidase and the studied extracts has revealed higher efficiency of antimutagene action of peroxidase.

Electrical behaviour of myenteric neurones in the gastric corpus of the guinea-pig.

PubMed Central

Schemann, M; Wood, J D

1989-01-01

1. Electrical behaviour of ganglion cells in the myenteric plexus of the guinea-pig stomach was investigated using intracellular recording methods. 2. Three subpopulations were identified and classified for convenience of discussion as gastric I, II and III neurones. Gastric I neurones were characterized by repetitive spike discharge during depolarizing current pulses and by higher input resistance than the other types. Gastric II neurones discharged one or two spikes only at the onset of long-lasting depolarizing current pulses. Gastric III neurones did not discharge spikes to depolarizing current pulses and had higher membrane potentials and lower input resistances than the other types. Non-stimulus evoked discharge ('spontaneous' discharge) did not occur in any of the neurones. 3. Resting membrane potentials were generated primarily by resting K+ conductance, but were smaller than the estimated K+ equilibrium potential. Analysis based on the constant field equation predicted lower K+ conductance in gastric I than in gastric III neurones. 4. Action potentials in gastric I and II neurones were suppressed or blocked by tetrodotoxin. Spikes that were broadened by tetraethylammonium appeared to have an inward component of Ca2+ current. 5. Hyperpolarizing after-potentials were associated with the spikes of both kinds of neurones. These after-potentials had much shorter duration (less than 300 ms) than the post-spike hyperpolarization of AH/type 2 intestinal neurones and unlike intestinal neurones there was no latency between the positive after-potential of the spike and the onset of the hyperpolarization. After-hyperpolarization in the gastric neurones was enhanced when the spikes were broadened by tetraethylammonium and was suppressed by removal of Ca2+ from the bathing solution. 6. Treatment with either tetraethylammonium or 4-aminopyridine enhanced excitability and induced 'spontaneously' occurring repetitive spike discharge. 7. The electrophysiological behaviour of gastric myenteric neurones differed significantly from intestinal neurones. This was interpreted as specialization of the neural networks that control and co-ordinate the activity of vastly different effector systems in the two regions of the alimentary canal. Images Fig. 1 PMID:2621607

Regulation of Local Ambient GABA Levels via Transporter-Mediated GABA Import and Export for Subliminal Learning.

PubMed

Hoshino, Osamu

2015-06-01

Perception of supraliminal stimuli might in general be reflected in bursts of action potentials (spikes), and their memory traces could be formed through spike-timing-dependent plasticity (STDP). Memory traces for subliminal stimuli might be formed in a different manner, because subliminal stimulation evokes a fraction (but not a burst) of spikes. Simulations of a cortical neural network model showed that a subliminal stimulus that was too brief (10 msec) to perceive transiently (more than about 500 msec) depolarized stimulus-relevant principal cells and hyperpolarized stimulus-irrelevant principal cells in a subthreshold manner. This led to a small increase or decrease in ongoing-spontaneous spiking activity frequency (less than 1 Hz). Synaptic modification based on STDP during this period effectively enhanced relevant synaptic weights, by which subliminal learning was improved. GABA transporters on GABAergic interneurons modulated local levels of ambient GABA. Ambient GABA molecules acted on extrasynaptic receptors, provided principal cells with tonic inhibitory currents, and contributed to achieving the subthreshold neuronal state. We suggest that ongoing-spontaneous synaptic alteration through STDP following subliminal stimulation may be a possible neuronal mechanism for leaving its memory trace in cortical circuitry. Regulation of local ambient GABA levels by transporter-mediated GABA import and export may be crucial for subliminal learning.

How can the auditory efferent system protect our ears from noise-induced hearing loss? Let us count the ways

NASA Astrophysics Data System (ADS)

Marshall, Lynne; Miller, Judi A. Lapsley

2015-12-01

It is a cause for some debate as to how the auditory olivocochlear (OC) efferent system could protect hearing from noise trauma. In this review, we examined physiological research to find mechanisms that could effectively attenuate the response to sound. For each purported mechanism, we indicate which part of the OC-efferent system is responsible for the function and the site of action. These mechanisms include basilar-membrane phase shifts at high stimulus levels; changes in outer-hair-cell stiffness and phase lag associated with efferent slow effects; small decreases in endocochlear potentials causing small decreases in outer- and inner-hair-cell output; low-spontaneous-rate and medium-spontaneous-rate fibers showing OC-induced decrements at high levels; auditory-nerve initial-peak reduction; OC effect increasing over minutes; cholinergic activation of anti-apoptotic pathways; and anti-excitotoxicity. There are clearly multiple opportunities for the OC-efferent system to protect the inner ear from noise trauma. From further exploration into the mechanisms outlined here, as well as to-be-discovered mechanisms, we will gain a greater understanding of the protective nature of the OC-efferent system. These findings could aid our ability to design better predictive tests for people at risk for noise-induced hearing loss.

Enhanced contractility of the rat stomach during suppression of angiotensin converting enzyme by captopril in vitro.

PubMed

Rani, R; Rao, K S

1991-04-01

1. Intragastric pressure (IGP) was used as an index, of the effect of serosal application of captopril (SQ 14,225; D-3-mercapto-2-methylpropanoyl-L-proline) on the contractility of rat stomach in vitro. 2. Captopril, at concentrations greater than 0.3 microM, enhanced the spontaneous gastric motility (GM) in a concentration-dependent manner whereas concentrations less than 0.3 microM selectively potentiated 4 nM bradykinin (BK)-evoked gastric contractions without significantly affecting the spontaneous GM. 3. The kallikrein inhibitor, aprotinin (100 u ml-1), markedly antagonized the enhanced GM to 1.4 microM captopril and BK (4 nM)-evoked contractions, without affecting the contractions evoked by angiotensin 1 (10 nM) and acetylcholine (0.4 microM). The angiotensin II antagonist, saralasin (50 microM) failed to mimic aprotinin. 4. The enhanced GM to captopril was markedly inhibited by tetrodotoxin (1 microM), and partially inhibited by atropine (1 microM). 5. These results indicate that in vitro, captopril (greater than 0.3 microM) enhances gastric contractility through kininase/ACE inhibitory action, presumably by increasing the concentration of undegraded tissue kinins and substance P. This motor response seems to be predominantly due to activation of the cholinergic neurones but non-cholinergic excitatory neurones are also involved.

Spontaneous breaking of scale invariance in a D = 3 U(N ) model with Chern-Simons gauge fields

DOE PAGES

Bardeen, William A.; Moshe, Moshe

2014-06-18

We study spontaneous breaking of scale invariance in the large N limit of three dimensional U(N ) κ Chern-Simons theories coupled to a scalar field in the fundamental representation. When a λ 6 ( Ø † · Ø) 3 self interaction term is added to the action we find a massive phase at a certain critical value for a combination of the λ(6) and ’t Hooft’s λ = N/κ couplings. This model attracted recent attention since at finite κ it contains a singlet sector which is conjectured to be dual to Vasiliev’s higher spin gravity on AdS 4. Our papermore » concentrates on the massive phase of the 3d boundary theory. We discuss the advantage of introducing masses in the boundary theory through spontaneous breaking of scale invariance.« less

Overcoming the Unhealthy Pursuit of Thinness: Reaction to the Québec Charter for a Healthy and Diverse Body Image

PubMed Central

Steiger, Howard

2012-01-01

Objectives. We examined the population reach, acceptability, and perceived potential of an initiative that developed a promotional tool for a healthy body image, the Québec Charter for a Healthy and Diverse Body Image. The Charter, developed through consensus building by a multisectoral, government-led task force, outlined actions to be undertaken by organizations or citizens to reduce media pressures favoring thinness. Methods. Six months after the Charter’s launch, we surveyed 1003 Québec residents aged 18 years or older about their knowledge of the Charter, their willingness to adhere to it, and their perceptions of its potential. Results. After minimal prompting, more than 35% of respondents recognized the Charter. About 33.7% were very favorable toward personally adhering to the Charter and 32.7% perceived the Charter as having high potential to sensitize people to negative consequences of disordered eating. Women showed greater likelihood and people with lesser education showed lower likelihood of spontaneous recognition. Conclusions. An initiative involving the creation of a body image Charter reaches a substantial portion of adults and is viewed as acceptable and potentially influential. PMID:22698056

Functional but Inefficient Kinesthetic Motor Imagery in Adolescents with Autism Spectrum Disorder.

PubMed

Chen, Ya-Ting; Tsou, Kuo-Su; Chen, Hao-Ling; Wong, Ching-Ching; Fan, Yang-Teng; Wu, Chien-Te

2018-03-01

Whether action representation in individuals with autism spectrum disorder (ASD) is deficient remains controversial, as previous studies of action observation or imitation report conflicting results. Here we investigated the characteristics of action representation in adolescents with ASD through motor imagery (MI) using a hand rotation and an object rotation task. Comparable with the typically-developing group, the individuals with ASD were able to spontaneously use kinesthetic MI to perform the hand rotation task, as manifested by the significant biomechanical effects. However, the ASD group performed significantly slower only in the hand rotation task, but not in the object rotation task. The findings suggest that the adolescents with ASD showed inefficient but functional kinesthetic MI, implicating that their action representation might be preserved.

Social Cohesion and Voluntary Associations

ERIC Educational Resources Information Center

Heuser, Brian L.

2005-01-01

Voluntary organizations exert great influence over how social norms and ethical codes are guided into action. As such, they have a significant impact on societal levels of social cohesion. Although social capital involves generalized trust becoming manifest as spontaneous sociability, social cohesion is determined by how that sociability is…

Chemical and mineralogical characterization of highly and less reactive coal from Northern Natal and Venda-Pafuri coalfields in South Africa

NASA Astrophysics Data System (ADS)

Kataka, M. O.; Matiane, A. R.; Odhiambo, B. D. O.

2018-01-01

Spontaneous combustion of coal is a major hazard associated with the coal mining industry over centuries. It also a major cause of underground fires in South African collieries and in opencast operations, spoil heaps and stockpiles. Spontaneous combustion incidents are manifested in all major aspects of coal mining namely, underground mining, surface mining, including during sea-borne transportation, storage and waste disposal. Previous studies indicate that there are various factors (both intrinsic and extrinsic) that influence the spontaneous combustion of coals. This paper characterizes highly reactive coal from the Vryheid coalfields and less reactive coal from at Venda-Pafuri coalfield, to identify and delineate some intrinsic coal parameters that are considered to be most critical in terms of heat 'generation' and relationships between the two coals types by tracing their similarities and differences in their spontaneous combustion parameters. Various tests were carried out to characterize these coals in terms of their intrinsic properties, namely: ultimate, proximate, petrographic analysis and Glasser spontaneous tests. The ultimate and proximate analysis showed that spontaneous coal has high contents of carbon, oxygen, and volatile matter as compared to non-spontaneous coal, making it more susceptible to spontaneous combustion. Non-spontaneous coal has higher ash content than the spontaneous coal. Furthermore, the petrographic analysis showed that spontaneous coal has high total reactivity compared to the non-spontaneous coal. Results from Glasser spontaneous test indicate that spontaneous coal absorbs more oxygen than non-spontaneous coal, which explains why spontaneous coal is more susceptible to spontaneous combustion. High reactive coal has low values of critical self-heating temperature (CSHT), indicating that this coal has potential of spontaneous ignition.

Effects of procaine on a central neuron of the snail, Achatina fulica Ferussac.

PubMed

Lin, Chia-Hsien; Tsai, Ming-Cheng

2005-02-18

Effects of procaine on a central neuron (RP1) of the giant African snail (Achatina fulica Ferussac) were studied pharmacologically. The RP1 neuron showed spontaneous firing of action potential. Extra-cellular application of procaine (10 mM) reversibly elicited bursts of potential. The bursts of potential elicited by procaine were not blocked after administration of (1) prazosin, propranolol, atropine, d-tubocurarine, (2) calcium-free solution, (3) ryanodine (4) pretreatment with KT-5720 or chelerythrine. The bursts of potential elicited by procaine were blocked by adding U73122 (10 microM) and the bursts of potential were decreased if physiological sodium ion was replaced with lithium ion or incubated with either neomycin (3.5 mM) or high magnesium solution (30 mM). Preatment with U73122 (10 microM) blocked the initiation of bursts of potential. Ruthenium red (100 microM) or caffeine (10 mM) facilitated the procaine-elicited bursts of potential. It is concluded that procaine reversibly elicits bursts of potential in the central snail neuron. This effect was not directly related to (1) the extra-cellular calcium ion fluxes, (2) the ryanodine sensitive calcium channels in the neuron, or (3) the PKC or PKA related messenger systems. The procaine-elicited bursts of potential were associated with the phospholipase activity and the calcium mobilization in the neuron.

Spontaneous sensorimotor coupling with multipart music.

PubMed

Hurley, Brian K; Martens, Peter A; Janata, Petr

2014-08-01

Music often evokes spontaneous movements in listeners that are synchronized with the music, a phenomenon that has been characterized as being in "the groove." However, the musical factors that contribute to listeners' initiation of stimulus-coupled action remain unclear. Evidence suggests that newly appearing objects in auditory scenes orient listeners' attention, and that in multipart music, newly appearing instrument or voice parts can engage listeners' attention and elicit arousal. We posit that attentional engagement with music can influence listeners' spontaneous stimulus-coupled movement. Here, 2 experiments-involving participants with and without musical training-tested the effect of staggering instrument entrances across time and varying the number of concurrent instrument parts within novel multipart music on listeners' engagement with the music, as assessed by spontaneous sensorimotor behavior and self-reports. Experiment 1 assessed listeners' moment-to-moment ratings of perceived groove, and Experiment 2 examined their spontaneous tapping and head movements. We found that, for both musically trained and untrained participants, music with more instruments led to higher ratings of perceived groove, and that music with staggered instrument entrances elicited both increased sensorimotor coupling and increased reports of perceived groove. Although untrained participants were more likely to rate music as higher in groove, trained participants showed greater propensity for tapping along, and they did so more accurately. The quality of synchronization of head movements with the music, however, did not differ as a function of training. Our results shed new light on the relationship between complex musical scenes, attention, and spontaneous sensorimotor behavior.

Applying Chemical Potential and Partial Pressure Concepts to Understand the Spontaneous Mixing of Helium and Air in a Helium-Inflated Balloon

ERIC Educational Resources Information Center

Jee-Yon Lee; Hee-Soo Yoo; Jong Sook Park; Kwang-Jin Hwang; Jin Seog Kim

2005-01-01

The spontaneous mixing of helium and air in a helium-inflated balloon is described in an experiment in which the partial pressure of the gases in the balloon are determined from the mole factions and the total pressure measured in the balloon. The results described provide a model for teaching concepts of partial pressure, chemical potential, and…

Examining educational attainment, prepregnancy smoking rate, and delay discounting as predictors of spontaneous quitting among pregnant smokers.

PubMed

White, Thomas J; Redner, Ryan; Skelly, Joan M; Higgins, Stephen T

2014-10-01

We investigated three potential predictors (educational attainment, prepregnancy smoking rate, and delay discounting [DD]) of spontaneous quitting among pregnant smokers. These predictors were examined alone and in combination with other potential predictors using study-intake assessments from controlled clinical trials examining the efficacy of financial incentives for smoking cessation and relapse prevention. Data from 349 pregnant women (231 continuing smokers and 118 spontaneous quitters) recruited from the greater Burlington, VT, area contributed to this secondary analysis, including psychiatric/sociodemographic characteristics, smoking characteristics, and performance on a computerized DD task. Educational attainment, smoking rate, and DD values were each significant predictors of spontaneous quitting in univariate analyses. A model examining those three predictors together retained educational attainment as a main effect and revealed a significant interaction of DD and smoking rate (i.e., DD was a significant predictor at lower but not higher smoking rates). A final model considering all potential predictors, included education, the interaction of DD and smoking rate, and five additional predictors (i.e., stress ratings, the belief that smoking during pregnancy will "greatly harm my baby," age of smoking initiation, marital status, and prior quit attempts during pregnancy). The study presented here contributes new knowledge on predictors of spontaneous quitting among pregnant smokers with substantive practical implications for reducing smoking during pregnancy. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Mapping spontaneous facial expression in people with Parkinson's disease: A multiple case study design.

PubMed

Gunnery, Sarah D; Naumova, Elena N; Saint-Hilaire, Marie; Tickle-Degnen, Linda

2017-01-01

People with Parkinson's disease (PD) often experience a decrease in their facial expressivity, but little is known about how the coordinated movements across regions of the face are impaired in PD. The face has neurologically independent regions that coordinate to articulate distinct social meanings that others perceive as gestalt expressions, and so understanding how different regions of the face are affected is important. Using the Facial Action Coding System, this study comprehensively measured spontaneous facial expression across 600 frames for a multiple case study of people with PD who were rated as having varying degrees of facial expression deficits, and created correlation matrices for frequency and intensity of produced muscle activations across different areas of the face. Data visualization techniques were used to create temporal and correlational mappings of muscle action in the face at different degrees of facial expressivity. Results showed that as severity of facial expression deficit increased, there was a decrease in number, duration, intensity, and coactivation of facial muscle action. This understanding of how regions of the parkinsonian face move independently and in conjunction with other regions will provide a new focus for future research aiming to model how facial expression in PD relates to disease progression, stigma, and quality of life.

Interaction of alcoholic extracts of hops with cocaine and paracetamol in mice.

PubMed

Horvat, Olga; Raskovic, Aleksandar; Jakovljevic, Vida; Sabo, Jan; Berenji, Janos

2007-01-01

This work describes a study of the interaction in the mouse model of alcoholic extracts of hops of Magnum, Aroma and wild genotypes with drugs that have excitatory effect on the cerebral cortex (cocaine) and analgesic action (paracetamol). Hop drying and preparation of the extracts were carried out according to standard pharmacological procedures for preparing total alcoholic extracts of dry herbs, consisting of one part of dry drug and two parts of 70% alcohol. The mice received four doses i.p. of 0.5% aqueous solutions of the above-mentioned extracts (10 ml/kg) 24, 16, 4 and 0.5 h prior to receiving cocaine (25 mg/kg) or paracetamol (80 mg/kg). The parameter investigated was the change in spontaneous motility of mice after combined treatment with the extracts and cocaine/paracetamol compared to control animals that received the same dose of the drug after treatment with physiological solution. Only the ethanolic extract of Magnum hops increased the spontaneous motility of mice, while none of the extracts showed analgesic action as measured by the hot-plate method. In the interaction with cocaine, the extract of Magnum hops suppressed almost completely the action of cocaine compared to controls. Extracts of the other hops also decreased the cocaine-induced locomotor activity of mice, but to a lesser extent. Hop extracts exhibited a significant pharmacological interaction with paracetamol, with the most pronounced increase in analgesic action being found for the ethanolic extract of Aroma hops and the tert-butanolic extract of wild hops.

4,5-Dichloro-2-octyl-4-isothiazolin-3-one (DCOIT) modifies synaptic transmission in hippocampal CA3 neurons of rats.

PubMed

Wakita, Masahito; Shoudai, Kiyomitsu; Oyama, Yasuo; Akaike, Norio

2017-10-01

4,5-Dichloro-2-octyl-4-isothiazolin-3-one (DCOIT) is an alternative to organotin antifoulants, such as tributyltin and triphenyltin. Since DCOIT is found in harbors, bays, and coastal areas worldwide, this chemical compound may have some impacts on ecosystems. To determine whether DCOIT possesses neurotoxic activity by modifying synaptic transmission, we examined the effects of DCOIT on synaptic transmission in a 'synaptic bouton' preparation of rat brain. DCOIT at concentrations of 0.03-1 μM increased the amplitudes of evoked synaptic currents mediated by GABA and glutamate, while it reduced the amplitudes of these currents at 3-10 μM. However, the currents elicited by exogenous applications of GABA and glutamate were not affected by DCOIT. DCOIT at 1-10 μM increased the frequency of spontaneous synaptic currents mediated by GABA. It also increased the frequency of glutamate-mediated spontaneous currents at0.3-10 μM. The frequencies of miniature synaptic currents mediated by GABA and glutamate, observed in the presence of tetrodotoxin under external Ca 2+ -free conditions, were increased by 10 μM DCOIT. With the repetitive applications of DCOIT, the frequency of miniature synaptic currents mediated by glutamate was not increased by the second and third applications of DCOIT. Voltage-dependent Ca 2+ channels were not affected by DCOIT, but DCOIT slowed the inactivation of voltage-dependent Na + channels. These results suggest that DCOIT increases Ca 2+ release from intracellular Ca 2+ stores, resulting in the facilitation of both action potential-dependent and spontaneous neurotransmission, possibly leading to neurotoxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spontaneous Facial Mimicry in Response to Dynamic Facial Expressions

ERIC Educational Resources Information Center

Sato, Wataru; Yoshikawa, Sakiko

2007-01-01

Based on previous neuroscientific evidence indicating activation of the mirror neuron system in response to dynamic facial actions, we hypothesized that facial mimicry would occur while subjects viewed dynamic facial expressions. To test this hypothesis, dynamic/static facial expressions of anger/happiness were presented using computer-morphing…

Type I and Type II Pyrethroid alterations in Spontaneous Bursting Parameters in Rat Cortical Networks measured Using Multielectrode Array Recordings

EPA Science Inventory

Pyrethroids are widely used in agricultural, industrial and residential settings to control insect pests. Pyrethroids prolong sodium channel inactivation, although their complete mode of action is not fully understood. We previously reported that permethrin (a Type I pyrethroid) ...

Understanding Schemas and Emotion in Early Childhood

ERIC Educational Resources Information Center

Arnold, Cath

2010-01-01

This book makes explicit connections between young children's spontaneous repeated actions and their representations of their emotional worlds. Drawing on the literature on schemas, attachment theory and family contexts, the author takes schema theory into the territory of the emotions, making it relevant to the social and emotional development…

Frequency of Use and Cost of Selected Anesthetic Induction and Neuromuscular Blocking Agents

DTIC Science & Technology

1997-10-02

with a known egg allergy caused by the use of egg lecithin to prepare the emulsion (Geniton, 1992). Pain may be experienced upon injection of propofol...spontaneous recovery (Bevan, 1994). It is completely and rapidly hydrolyzed by plasma cholinesterase (pseudocholinesterase) which terminates its action

ACTIONS OF PYRETHROID INSECTICIDES ON THE SPONTANEOUS RELEASE OF GLUTAMATE FROM CULTURED HIPPOCAMPAL NEURONS.

EPA Science Inventory

Pyrethroid insecticides increase the excitability of the central and peripheral nervous systems. Modulation of voltage-gated sodium channels is likely to play a primary role in this effect, but recent studies have suggested that pyrethroid effects on other ion channels may contri...

Contribution of thermoelectric and electrochemical effects to spontaneous potential signals induced by water injection into hydrocarbon reservoirs

NASA Astrophysics Data System (ADS)

Gulamali, M. Y.; Saunders, J. H.; Jackson, M.; Pain, C. C.

2009-12-01

Recent work has demonstrated that downhole measurements of streaming potential, using electrodes mounted on the outside of insulated casing, may be used to inform production strategies in oil and gas reservoirs. However, spontaneous potentials due to thermoelectric and/or electrochemical effects may also be present during production and may contribute to the signal measured at the production well. We present a workflow to numerically model spontaneous potentials in the subsurface and ascertain their magnitude in oil reservoirs during production. Our results suggest that the injection of seawater, which typically has a different temperature and salinity to the formation brine, leads to the generation of both thermoelectric and electrochemical potential signals which may be measured at the production well. We observe a peak in the thermoelectric potential before and after the temperature front, with a change in sign occurring close to the midpoint of the front, and the signal decaying with distance from the front. The electrochemical potential has a similar profile, with a change in sign occurring close to the location of the salinity front. In both cases, the absolute magnitude of the signal is related to the overall temperature and/or salinity contrast between the injected fluids and the formation brine, and the magnitude of the thermoelectric or electrochemical coupling coefficient. The lag in the temperature front relative to the saturation front leads to a negligible thermoelectric potential signal at the production well until long after water breakthrough occurs. In contrast, the electrochemical potential contributes significantly to the spontaneous potential measured at the production well before the waterfront arrives, as the salinity front and the saturation front coincide. However, the dependency of the thermoelectric and electrochemical coupling coefficients upon temperature and/or salinity is still uncertain, especially at partial water saturation. We have used the maximum theoretical limit, in the case of the perfect membrane, to estimate these parameters. These results imply that measurements of the spontaneous potential at a production well will combine contributions from both streaming and electrochemical effects, and may be used to detect an advancing waterfront some time before water breakthrough occurs at the well. Moreover, inversion of the measured signals could be used to determine the water saturation in the vicinity of the well, and to regulate flow into the well using control valves in order to maintain or increase oil production.

Pertussis toxin inhibits somatostatin-induced K/sup +/ conductance in human pituitary tumor cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamashita, N.; Kojima, I.; Shibuya, N.

1987-07-01

The effect of pertussis toxin on somatostatin-induced K/sup +/ current was examined in dissociated human pituitary tumor cells obtained from two acromegalic patients. Somatostatin-induced hyperpolarization or K/sup +/ current was observed in 20 of 23 cells in adenoma 1 and 10 of 11 cells in adenoma 2. After treatment with pertussis toxin for 24 h, these responses were completely suppressed (0/14 in adenoma, 1, 0/10 in adenoma 2). Spontaneous action potentials, K/sup +/, Na/sup +/, and Ca/sup 2 +/ currents were well preserved after pertussis toxin treatment. When crude membrane fraction was incubated with (/sup 32/P)NAD, a 41K protein wasmore » ADP-ribosylated by pertussis toxin. Hormone release was inhibited by somatostatin and this inhibition was blocked by pertussis toxin treatment.« less

Electrophysiology of Extraocular Cranial Nerves: Oculomotor, Trochlear, and Abducens Nerve.

PubMed

Hariharan, Praveen; Balzer, Jeffery R; Anetakis, Katherine; Crammond, Donald J; Thirumala, Parthasarathy D

2018-01-01

The utility of extraocular cranial nerve electrophysiologic recordings lies primarily in the operating room during skull base surgeries. Surgical manipulation during skull base surgeries poses a risk of injury to multiple cranial nerves, including those innervating extraocular muscles. Because tumors distort normal anatomic relationships, it becomes particularly challenging to identify cranial nerve structures. Studies have reported the benefits of using intraoperative spontaneous electromyographic recordings and compound muscle action potentials evoked by electrical stimulation in preventing postoperative neurologic deficits. Apart from surgical applications, electromyography of extraocular muscles has also been used to guide botulinum toxin injections in patients with strabismus and as an adjuvant diagnostic test in myasthenia gravis. In this article, we briefly review the rationale, current available techniques to monitor extraocular cranial nerves, technical difficulties, clinical and surgical applications, as well as future directions for research.

AgRP and MC3/4 receptor agonists both inhibit excitatory hypothalamic ventromedial nucleus neurons

PubMed Central

Fu, Li-Ying; van den Pol, Anthony N.

2009-01-01

Anorexigenic melanocortins decrease food intake by activating MC3/MC4 receptors (MC3/4R); the prevailing view is that the orexigenic neuropeptide AgRP exerts the opposite action by acting as an antagonist at MC3/MC4 receptors. 370 VMH glutamatergic neurons were studied using whole-cell recording in hypothalamic slices from a novel mouse expressing GFP under control of the vGluT2 promoter. Massive numbers of GFP-expressing VMH dendrites extended out of the core of the nucleus into the surrounding cell-poor shell. VMH dendrites received frequent appositions from AgRP immunoreactive axons in the shell of the nucleus, but not the core, suggesting that AgRP may influence target VMH neurons. Alpha-MSH, MTII, and selective MC3R or MC4R agonists were all inhibitory, reducing the spontaneous firing rate and hyperpolarizing vGluT2 neurons. The MC3/4R antagonist SHU9119 was excitatory. Unexpectedly, AgRP did not attenuate MTII actions on these neurons; instead these two compounds showed an additive inhibitory effect. In the absence of synaptic activity, no hyperpolarization or change in input resistance was evoked by either MTII or AgRP, suggesting indirect actions. Consistent with this view, MTII increased the frequency of spontaneous and miniature IPSCs. In contrast, the mechanism of AgRP inhibition was dependent on presynaptic inhibition of EPSCs mediated by Gi/Go proteins, and was attenuated by pertussis toxin and NF023, inconsistent with mediation by Gs proteins associated with MC receptors. Together, our data suggest that the mechanism of AgRP actions on these excitatory VMH cells appears to be independent of the actions of melanocortins on MC receptors. PMID:18495877

Free radical reaction characteristics of coal low-temperature oxidation and its inhibition method.

PubMed

Li, Zenghua; Kong, Biao; Wei, Aizhu; Yang, Yongliang; Zhou, Yinbo; Zhang, Lanzhun

2016-12-01

Study on the mechanism of coal spontaneous combustion is significant for controlling fire disasters due to coal spontaneous combustion. The free radical reactions can explain the chemical process of coal at low-temperature oxidation. Electron spin resonance (ESR) spectroscopy was used to measure the change rules of the different sorts and different granularity of coal directly; ESR spectroscopy chart of free radicals following the changes of temperatures was compared by the coal samples applying air and blowing nitrogen, original coal samples, dry coal samples, and demineralized coal samples. The fragmentation process was the key factor of producing and initiating free radical reactions. Oxygen, moisture, and mineral accelerated the free radical reactions. Combination of the free radical reaction mechanism, the mechanical fragmentation leaded to the elevated CO concentration, fracturing of coal pillar was more prone to spontaneous combustion, and spontaneous combustion in goaf accounted for a large proportion of the fire in the mine were explained. The method of added diphenylamine can inhibit the self-oxidation of coal effectively, the action mechanism of diphenylamine was analyzed by free radical chain reaction, and this research can offer new method for the development of new flame retardant.

Progesterone to prevent spontaneous preterm birth

PubMed Central

Romero, Roberto; Yeo, Lami; Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Hassan, Sonia

2014-01-01

Summary Preterm birth is the leading cause of perinatal morbidity and mortality worldwide, and its prevention is an important healthcare priority. Preterm parturition is one of the ‘great obstetrical syndromes’ and is caused by multiple etiologies. One of the mechanisms of disease is the untimely decline in progesterone action, which can be manifested by a sonographic short cervix in the midtrimester. The detection of a short cervix in the midtrimester is a powerful risk factor for preterm delivery. Vaginal progesterone can reduce the rate of preterm delivery by 45%, and the rate of neonatal morbidity (admission to neonatal intensive care unit, respiratory distress syndrome, need for mechanical ventilation, etc.). To prevent one case of spontaneous preterm birth <33 weeks of gestation, 12 patients with a short cervix would need to be treated. Vaginal progesterone reduces the rate of spontaneous preterm birth in women with a short cervix both with and without a prior history of preterm birth. In patients with a prior history of preterm birth, vaginal progesterone is as effective as cervical cerclage to prevent preterm delivery. 17α-Hydroxyprogesterone caproate has not been shown to be effective in reducing the rate of spontaneous preterm birth in women with a short cervix. PMID:24315687

Mechanisms of morphine enhancement of spontaneous seizure activity.

PubMed

Saboory, Ehsan; Derchansky, Miron; Ismaili, Mohammed; Jahromi, Shokrollah S; Brull, Richard; Carlen, Peter L; El Beheiry, Hossam

2007-12-01

High-dose opioid therapy can precipitate seizures; however, the mechanism of such a dangerous adverse effect remains poorly understood. The aim of our study was to determine whether the neuroexcitatory activity of high-dose morphine is mediated by selective stimulation of opioid receptors. Mice hippocampi were resected intact and bathed in low magnesium artificial cerebrospinal fluid to induce spontaneous seizure-like events recorded from CA1 neurons. Application of morphine had a biphasic effect on the recorded spontaneous seizure-like events. In a low concentration (10 microM), morphine depressed electrographic seizure activity. Higher morphine concentrations (30 and 100 microM) enhanced seizure activity in an apparent dose-dependent manner. Naloxone, a nonselective opiate antagonist blocked the proconvulsant action of morphine. Selective mu and kappa opiate receptor agonists and antagonists enhanced and suppressed the spontaneous seizure activity, respectively. On the contrary, delta opioid receptor ligands did not have an effect. The proseizure effect of morphine is mediated through selective stimulation of mu and kappa opiate receptors but not the activation of the delta receptor system. The observed dose-dependent mechanism of morphine neuroexcitation underscores careful adjustment and individualized opioid dosing in the clinical setting.

[Peripheral mechanisms of action of oxatriazolium-5-olate derivative 3-(3-[1,2,4]-triazolo)oxatriazolium-5-olate in spontaneously hypertensive rats].

PubMed

Artem'eva, M M; Postnikov, A B; Akinfieva, O V; Daliger, I L; Shevelev, S A; Medvedev, O S; Medvedeva, N A

2012-01-01

It is shown that 3-(3-[1,2,4]-triazolo)-oxatriazolium-5-olate (azasidnon-6) can act directly on the vascular wall of isolated segments of caudal ventral artery of SHR rats. Using heme-dependent soluble guanyl cyclase inhibitor 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), it has been found that one of the possible mechanisms of azasidnon-6 vasodilatory action includes heme-dependent activation of a soluble form of guanylate cyclase.

Angiotensin Receptor Blocker Losartan Inhibits Spontaneous Motility of Isolated Human Ureter.

PubMed

Jankovic, Slobodan M; Stojadinovic, Dobrivoje; Stojadinovic, Miroslav; Jankovic, Snezana V; Djuric, Janko M; Stojic, Isidora; Kostic, Marina

2016-12-01

Ureteral motility is essential for elimination of intraluminal stones, and it may be adversely affected by cardiovascular drugs that a patient is taking chronically. The aim of our study was to test whether ACE inhibitors and an angiotensin receptor blocker may influence spontaneous contractions of isolated human ureter. Both phasic and tonic contractions of the isolated ureteral segments taken from 10 patients were measured as changes of the longitudinal tension or pressure recordings. Captopril, enalapril and losartan were separately added to the organ baths cumulatively. While enalapril (2.7 × 10 -7 -3.9 × 10 -4  M) and captopril (6.1 × 10 -7 -2.7 × 10 -3  M) did not affect either spontaneous activity or tone of isolated ureteral segments, losartan (2.9 × 10 -7 -4.2 × 10 -4  M) caused concentration-dependent inhibition of spontaneous contractions of the segments (50 % effective concentration (EC 50 ) = 13.46 ± 1.80 × 10 -6  M; F = 10.72, r = 0.79, p < 0.001). Due to differences in molecular mechanism of action, angiotensin receptor blocker losartan does and ACE inhibitors captopril and enalapril do not inhibit spontaneous contractions of isolated human ureter.

The PLC/IP3R/PKC Pathway is Required for Ethanol-enhanced GABA Release

PubMed Central

Kelm, M. Katherine; Weinberg, Richard J.; Criswell, Hugh E.; Breese, George R.

2010-01-01

Summary Research on the actions of ethanol at the GABAergic synapse has traditionally focused on postsynaptic mechanisms, but recent data demonstrate that ethanol also increases both evoked and spontaneous GABA release in many brain regions. Using whole-cell voltage-clamp recordings, we previously showed that ethanol increases spontaneous GABA release at the rat interneuron-Purkinje cell synapse. This presynaptic ethanol effect is dependent on calcium release from internal stores, possibly through activation of inositol 1,4,5-trisphosphate receptors (IP3Rs). After confirming that ethanol targets vesicular GABA release, in the present study we used electron microscopic immunohistochemistry to demonstrate that IP3Rs are located in presynaptic terminals of cerebellar interneurons. Activation of IP3Rs requires binding of IP3, generated through activation of phospholipase C (PLC). We find that the PLC antagonist edelfosine prevents ethanol from increasing spontaneous GABA release. Diacylglycerol generated by PLC and calcium released by activation of the IP3R activate protein kinase C (PKC). Ethanol-enhanced GABA release was blocked by two PKC antagonists, chelerythrine and calphostin C. When a membrane impermeable PKC antagonist, PKC (19-36), was delivered intracellularly to the postsynaptic neuron, ethanol continued to increase spontaneous GABA release. Overall, these results suggest that activation of the PLC/IP3R/PKC pathway is necessary for ethanol to increase spontaneous GABA release from presynaptic terminals onto Purkinje cells. PMID:20206640

Electrical stimulation of dorsal root entry zone attenuates wide-dynamic range neuronal activity in rats

PubMed Central

Yang, Fei; Zhang, Chen; Xu, Qian; Tiwari, Vinod; He, Shao-Qiu; Wang, Yun; Dong, Xinzhong; Vera-Portocarrero, Louis P.; Wacnik, Paul W.; Raja, Srinivasa N.; Guan, Yun

2014-01-01

Objectives Recent clinical studies suggest that neurostimulation at the dorsal root entry zone (DREZ) may alleviate neuropathic pain. However, the mechanisms of action for this therapeutic effect are unclear. Here, we examined whether DREZ stimulation inhibits spinal wide-dynamic-range (WDR) neuronal activity in nerve-injured rats. Materials and Methods We conducted in vivo extracellular single-unit recordings of WDR neurons in rats after an L5 spinal nerve ligation (SNL) or sham surgery. We set bipolar electrical stimulation (50 Hz, 0.2 ms, 5 min) of the DREZ at the intensity that activated only Aα/β-fibers by measuring the lowest current at which DREZ stimulation evoked a peak antidromic sciatic Aα/β-compound action potential without inducing an Aδ/C-compound action potential (i.e., Ab1). Results The elevated spontaneous activity rate of WDR neurons in SNL rats [n=25; data combined from day 14–16 (n = 15) and day 45–75 post-SNL groups (n=10)] was significantly decreased from the pre-stimulation level (p<0.01) at 0–15 min and 30–45 min post-stimulation. In both sham-operated (n=8) and nerve-injured rats, DREZ stimulation attenuated the C-component, but not A-component, of the WDR neuronal response to graded intracutaneous electrical stimuli (0.1–10 mA, 2 ms) applied to the skin receptive field. Further, DREZ stimulation blocked windup (a short form of neuronal sensitization) to repetitive noxious stimuli (0.5 Hz) at 0–15 min in all groups (p<0.05). Conclusions Attenuation of WDR neuronal activity may contribute to DREZ stimulation-induced analgesia. This finding supports the notion that DREZ may be a useful target for neuromodulatory control of pain. PMID:25308522

Patch-Clamp Recording from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Improving Action Potential Characteristics through Dynamic Clamp

PubMed Central

Veerman, Christiaan C.; Zegers, Jan G.; Mengarelli, Isabella; Bezzina, Connie R.

2017-01-01

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for studying inherited cardiac arrhythmias and developing drug therapies to treat such arrhythmias. Unfortunately, until now, action potential (AP) measurements in hiPSC-CMs have been hampered by the virtual absence of the inward rectifier potassium current (IK1) in hiPSC-CMs, resulting in spontaneous activity and altered function of various depolarising and repolarising membrane currents. We assessed whether AP measurements in “ventricular-like” and “atrial-like” hiPSC-CMs could be improved through a simple, highly reproducible dynamic clamp approach to provide these cells with a substantial IK1 (computed in real time according to the actual membrane potential and injected through the patch-clamp pipette). APs were measured at 1 Hz using perforated patch-clamp methodology, both in control cells and in cells treated with all-trans retinoic acid (RA) during the differentiation process to increase the number of cells with atrial-like APs. RA-treated hiPSC-CMs displayed shorter APs than control hiPSC-CMs and this phenotype became more prominent upon addition of synthetic IK1 through dynamic clamp. Furthermore, the variability of several AP parameters decreased upon IK1 injection. Computer simulations with models of ventricular-like and atrial-like hiPSC-CMs demonstrated the importance of selecting an appropriate synthetic IK1. In conclusion, the dynamic clamp-based approach of IK1 injection has broad applicability for detailed AP measurements in hiPSC-CMs. PMID:28867785

Treatment of allergic rhinitis and urticaria: a review of the newest antihistamine drug bilastine.

PubMed

Wang, Xue Yan; Lim-Jurado, Margaret; Prepageran, Narayanan; Tantilipikorn, Pongsakorn; Wang, De Yun

2016-01-01

Allergic rhinitis and urticaria are common allergic diseases that may have a major negative impact on patients' quality of life. Bilastine, a novel new-generation antihistamine that is highly selective for the H1 histamine receptor, has a rapid onset and prolonged duration of action. This agent does not interact with the cytochrome P450 system and does not undergo significant metabolism in humans, suggesting that it has very low potential for drug-drug interactions, and does not require dose adjustment in renal impairment. As bilastine is not metabolized and is excreted largely unchanged, hepatic impairment is not expected to increase systemic exposure above the drug's safety margin. Bilastine has demonstrated similar efficacy to cetirizine and desloratadine in patients with seasonal allergic rhinitis and, in a Vienna Chamber study, a potentially longer duration of action than fexofenadine in patients with asymptomatic seasonal allergic rhinitis. It has also shown significant efficacy (similar to that of cetirizine) and safety in the long-term treatment of perennial allergic rhinitis. Bilastine showed similar efficacy to levocetirizine in patients with chronic spontaneous urticaria and can be safely used at doses of up to fourfold higher than standard dosage (80 mg once daily). The fourfold higher than standard dose is specified as an acceptable second-line treatment option for urticaria in international guidelines. Bilastine is generally well tolerated, both at standard and at supratherapeutic doses, appears to have less sedative potential than other second-generation antihistamines, and has no cardiotoxicity. Based on its pharmacokinetic properties, efficacy, and tolerability profile, bilastine will be valuable in the management of allergic rhinitis and urticaria.

Spatially defined InsP3-mediated signaling in embryonic stem cell-derived cardiomyocytes.

PubMed

Kapoor, Nidhi; Maxwell, Joshua T; Mignery, Gregory A; Will, David; Blatter, Lothar A; Banach, Kathrin

2014-01-01

The functional role of inositol 1,4,5-trisphosphate (InsP3) signaling in cardiomyocytes is not entirely understood but it was linked to an increased propensity for triggered activity. The aim of this study was to determine how InsP3 receptors can translate Ca(2+) release into a depolarization of the plasma membrane and consequently arrhythmic activity. We used embryonic stem cell-derived cardiomyocytes (ESdCs) as a model system since their spontaneous electrical activity depends on InsP3-mediated Ca(2+) release. [InsP3]i was monitored with the FRET-based InsP3-biosensor FIRE-1 (Fluorescent InsP3 Responsive Element) and heterogeneity in sub-cellular [InsP3]i was achieved by targeted expression of FIRE-1 in the nucleus (FIRE-1nuc) or expression of InsP3 5-phosphatase (m43) localized to the plasma membrane. Spontaneous activity of ESdCs was monitored simultaneously as cytosolic Ca(2+) transients (Fluo-4/AM) and action potentials (current clamp). During diastole, the diastolic depolarization was paralleled by an increase of [Ca(2+)]i and spontaneous activity was modulated by [InsP3]i. A 3.7% and 1.7% increase of FIRE-1 FRET ratio and 3.0 and 1.5 fold increase in beating frequency was recorded upon stimulation with endothelin-1 (ET-1, 100 nmol/L) or phenylephrine (PE, 10 µmol/L), respectively. Buffering of InsP3 by FIRE-1nuc had no effect on the basal frequency while attenuation of InsP3 signaling throughout the cell (FIRE-1), or at the plasma membrane (m43) resulted in a 53.7% and 54.0% decrease in beating frequency. In m43 expressing cells the response to ET-1 was completely suppressed. Ca(2+) released from InsP3Rs is more effective than Ca(2+) released from RyRs to enhance INCX. The results support the hypothesis that in ESdCs InsP3Rs form a functional signaling domain with NCX that translates Ca(2+) release efficiently into a depolarization of the membrane potential.

Molecular Expression and Pharmacological Evidence for a Functional Role of Kv7 Channel Subtypes in Guinea Pig Urinary Bladder Smooth Muscle

PubMed Central

Afeli, Serge A. Y.; Malysz, John; Petkov, Georgi V.

2013-01-01

Voltage-gated Kv7 (KCNQ) channels are emerging as essential regulators of smooth muscle excitability and contractility. However, their physiological role in detrusor smooth muscle (DSM) remains to be elucidated. Here, we explored the molecular expression and function of Kv7 channel subtypes in guinea pig DSM by RT-PCR, qRT-PCR, immunohistochemistry, electrophysiology, and isometric tension recordings. In whole DSM tissue, mRNAs for all Kv7 channel subtypes were detected in a rank order: Kv7.1~Kv7.2Kv7.3~Kv7.5Kv7.4. In contrast, freshly-isolated DSM cells showed mRNA expression of: Kv7.1~Kv7.2Kv7.5Kv7.3~Kv7.4. Immunohistochemical confocal microscopy analyses of DSM, conducted by using co-labeling of Kv7 channel subtype-specific antibodies and α-smooth muscle actin, detected protein expression for all Kv7 channel subtypes, except for the Kv7.4, in DSM cells. L-364373 (R-L3), a Kv7.1 channel activator, and retigabine, a Kv7.2-7.5 channel activator, inhibited spontaneous phasic contractions and the 10-Hz electrical field stimulation (EFS)-induced contractions of DSM isolated strips. Linopiridine and XE991, two pan-Kv7 (effective at Kv7.1-Kv7.5 subtypes) channel inhibitors, had opposite effects increasing DSM spontaneous phasic and 10 Hz EFS-induced contractions. EFS-induced DSM contractions generated by a wide range of stimulation frequencies were decreased by L-364373 (10 µM) or retigabine (10 µM), and increased by XE991 (10 µM). Retigabine (10 µM) induced hyperpolarization and inhibited spontaneous action potentials in freshly-isolated DSM cells. In summary, Kv7 channel subtypes are expressed at mRNA and protein levels in guinea pig DSM cells. Their pharmacological modulation can control DSM contractility and excitability; therefore, Kv7 channel subtypes provide potential novel therapeutic targets for urinary bladder dysfunction. PMID:24073284

The Novel KV7.2/KV7.3 Channel Opener ICA-069673 Reveals Subtype-Specific Functional Roles in Guinea Pig Detrusor Smooth Muscle Excitability and Contractility

PubMed Central

Provence, Aaron; Malysz, John

2015-01-01

The physiologic roles of voltage-gated KV7 channel subtypes (KV7.1–KV7.5) in detrusor smooth muscle (DSM) are poorly understood. Here, we sought to elucidate the functional roles of KV7.2/KV7.3 channels in guinea pig DSM excitability and contractility using the novel KV7.2/KV7.3 channel activator ICA-069673 [N-(2-chloro-5-pyrimidinyl)-3,4-difluorobenzamide]. We employed a multilevel experimental approach using Western blot analysis, immunocytochemistry, isometric DSM tension recordings, fluorescence Ca2+ imaging, and perforated whole-cell patch-clamp electrophysiology. Western blot experiments revealed the protein expression of KV7.2 and KV7.3 channel subunits in DSM tissue. In isolated DSM cells, immunocytochemistry with confocal microscopy further confirmed protein expression for KV7.2 and KV7.3 channel subunits, where they localize within the vicinity of the cell membrane. ICA-069673 inhibited spontaneous phasic, pharmacologically induced, and nerve-evoked contractions in DSM isolated strips in a concentration-dependent manner. The inhibitory effects of ICA-069673 on DSM spontaneous phasic and tonic contractions were abolished in the presence of the KV7 channel inhibitor XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride]. Under conditions of elevated extracellular K+ (60 mM), the effects of ICA-069673 on DSM tonic contractions were significantly attenuated. ICA-069673 decreased the global intracellular Ca2+ concentration in DSM cells, an effect blocked by the L-type Ca2+ channel inhibitor nifedipine. ICA-069673 hyperpolarized the membrane potential and inhibited spontaneous action potentials of isolated DSM cells, effects that were blocked in the presence of XE991. In conclusion, using the novel KV7.2/KV7.3 channel activator ICA-069673, this study provides strong evidence for a critical role for the KV7.2- and KV7.3-containing channels in DSM function at both cellular and tissue levels. PMID:26087697

The Novel KV7.2/KV7.3 Channel Opener ICA-069673 Reveals Subtype-Specific Functional Roles in Guinea Pig Detrusor Smooth Muscle Excitability and Contractility.

PubMed

Provence, Aaron; Malysz, John; Petkov, Georgi V

2015-09-01

The physiologic roles of voltage-gated KV7 channel subtypes (KV7.1-KV7.5) in detrusor smooth muscle (DSM) are poorly understood. Here, we sought to elucidate the functional roles of KV7.2/KV7.3 channels in guinea pig DSM excitability and contractility using the novel KV7.2/KV7.3 channel activator ICA-069673 [N-(2-chloro-5-pyrimidinyl)-3,4-difluorobenzamide]. We employed a multilevel experimental approach using Western blot analysis, immunocytochemistry, isometric DSM tension recordings, fluorescence Ca(2+) imaging, and perforated whole-cell patch-clamp electrophysiology. Western blot experiments revealed the protein expression of KV7.2 and KV7.3 channel subunits in DSM tissue. In isolated DSM cells, immunocytochemistry with confocal microscopy further confirmed protein expression for KV7.2 and KV7.3 channel subunits, where they localize within the vicinity of the cell membrane. ICA-069673 inhibited spontaneous phasic, pharmacologically induced, and nerve-evoked contractions in DSM isolated strips in a concentration-dependent manner. The inhibitory effects of ICA-069673 on DSM spontaneous phasic and tonic contractions were abolished in the presence of the KV7 channel inhibitor XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride]. Under conditions of elevated extracellular K(+) (60 mM), the effects of ICA-069673 on DSM tonic contractions were significantly attenuated. ICA-069673 decreased the global intracellular Ca(2+) concentration in DSM cells, an effect blocked by the L-type Ca(2+) channel inhibitor nifedipine. ICA-069673 hyperpolarized the membrane potential and inhibited spontaneous action potentials of isolated DSM cells, effects that were blocked in the presence of XE991. In conclusion, using the novel KV7.2/KV7.3 channel activator ICA-069673, this study provides strong evidence for a critical role for the KV7.2- and KV7.3-containing channels in DSM function at both cellular and tissue levels. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Proconvulsant Actions of Intrahippocampal Botulinum Neurotoxin B in the Rat

PubMed Central

Bröer, Sonja; Zolkowska, Dorota; Gernert, Manuela; Rogawski, Michael A.

2013-01-01

Botulinum neurotoxins (BoNTs) may affect the excitability of brain circuits by inhibiting neurotransmitter release at central synapses. There is evidence that local delivery of BoNT serotypes A and E, which target SNAP-25, a component of the release machinery specific to excitatory synapses, can inhibit seizure generation. BoNT serotype B (BoNT/B) targets VAMP2, which is expressed in both excitatory and inhibitory terminals. Here we assessed the effects of unilateral intrahippocampal infusion of BoNT/B in the rat on intravenous pentylenetetrazol (PTZ) seizure thresholds, and on the expression of spontaneous behavioral and electrographic seizures. Infusion of BoNT/B (500 and 1000 unit) by convection-enhanced delivery caused a reduction in myoclonic twitch and clonic seizure thresholds in response to intravenous PTZ beginning about 6 days after the infusion. Handling-evoked and spontaneous convulsive seizures were observed in many BoNT/B-treated animals but not in vehicle-treated controls. Spontaneous electrographic seizure discharges were recorded in the dentate gyrus of animals that received local BoNT/B infusion. In addition, there was an increased frequency of interictal epileptiform spikes and sharp waves at the same recording site. BoNT/B treated animals also exhibited tactile hyperresponsivity in comparison with vehicle-treated controls. This is the first demonstration that BoNT/B causes a delayed proconvulsant action when infused into the hippocampus. Local infusion of BoNT/B could be useful as a focal epilepsy model. PMID:23906638

Effects of Antiepileptic Drugs on Spontaneous Recurrent Seizures in a Novel Model of Extended Hippocampal Kindling in Mice.

PubMed

Song, Hongmei; Tufa, Uilki; Chow, Jonathan; Sivanenthiran, Nila; Cheng, Chloe; Lim, Stellar; Wu, Chiping; Feng, Jiachun; Eubanks, James H; Zhang, Liang

2018-01-01

Epilepsy is a common neurological disorder characterized by naturally-occurring spontaneous recurrent seizures and comorbidities. Kindling has long been used to model epileptogenic mechanisms and to assess antiepileptic drugs. In particular, extended kindling can induce spontaneous recurrent seizures without gross brain lesions, as seen clinically. To date, the development of spontaneous recurrent seizures following extended kindling, and the effect of the antiepileptic drugs on these seizures are not well understood. In the present study we aim to develop a mouse model of extended hippocampal kindling for the first time. Once established, we plan to evaluate the effect of three different antiepileptic drugs on the development of the extended-hippocampal-kindled-induced spontaneous recurrent seizures. Male C57 black mice were used for chronic hippocampal stimulations or handling manipulations (twice daily for up to 70 days). Subsequently, animals underwent continuous video/EEG monitoring for seizure detection. Spontaneous recurrent seizures were consistently observed in extended kindled mice but no seizures were detected in the control animals. The aforementioned seizures were generalized events characterized by hippocampal ictal discharges and concurrent motor seizures. Incidence and severity of the seizures was relatively stable while monitored over a few months after termination of the hippocampal stimulation. Three antiepileptic drugs with distinct action mechanisms were tested: phenytoin, lorazepam and levetiracetam. They were applied via intra-peritoneal injections at anticonvulsive doses and their effects on the spontaneous recurrent seizures were analyzed 10-12 h post-injection. Phenytoin (25 mg/kg) and levetiracetam (400 mg/kg) abolished the spontaneous recurrent seizures. Lorazepam (1.5 mg/kg) decreased motor seizure severity but did not reduce the incidence and duration of corresponding hippocampal discharges, implicating its inhibitory effects on seizure spread. No gross brain lesions were observed in a set of extended hippocampal kindled mice submitted to histological evaluation. All these data suggests that our model could be considered as a novel mouse model of extended hippocampal kindling. Some limitations remain to be considered.

What is the Essence of Hypnosis?

PubMed

Dell, Paul F

2017-01-01

The author explores the nature of hypnosis, which he characterizes as a motivated mode of neural functioning that enables most humans to alter, to varying degrees, their experience of body, self, actions, and world. The essence of hypnosis is not to be found in hetero-hypnosis; instead, it lies in the spontaneous self-activation of that mode of neural functioning. The hypnosis field has substantially lost sight of spontaneous self-activation, because the word hypnosis is usually used to mean hetero-hypnosis. Self-activation of this mode of neural functioning is the necessary sine qua non of hypnotic psychopathology. Moreover, self-activation of trance is the characteristic hypnotic behavior of a distinct subset of highly hypnotizable individuals.

Costs and consequences of abortions to women and their households: a cross-sectional study in Ouagadougou, Burkina Faso

PubMed Central

Ilboudo, Patrick G C; Greco, Giulia; Sundby, Johanne; Torsvik, Gaute

2015-01-01

Little is known about the costs and consequences of abortions to women and their households. Our aim was to study both costs and consequences of induced and spontaneous abortions and complications. We carried out a cross-sectional study between February and September 2012 in Ouagadougou, the capital city of Burkina Faso. Quantitative data of 305 women whose pregnancy ended with either an induced or a spontaneous abortion were prospectively collected on sociodemographic, asset ownership, medical and health expenditures including pre-referral costs following the patient’s perspective. Descriptive analysis and regression analysis of costs were performed. We found that women with induced abortion were often single or never married, younger, more educated and had earlier pregnancies than women with spontaneous abortion. They also tended to be more often under parents’ guardianship compared with women with spontaneous abortion. Women with induced abortion paid much more money to obtain abortion and treatment of the resulting complications compared with women with spontaneous abortion: US$89 (44 252 CFA ie franc of the African Financial Community) vs US$56 (27 668 CFA). The results also suggested that payments associated with induced abortion were catastrophic as they consumed 15% of the gross domestic product per capita. Additionally, 11–16% of total households appeared to have resorted to coping strategies in order to face costs. Both induced and spontaneous abortions may incur high expenses with short-term economic repercussions on households’ poverty. Actions are needed in order to reduce the financial burden of abortion costs and promote an effective use of contraceptives. PMID:24829315

Arginine vasopressin antagonizes the effects of prostaglandin E2 on the spontaneous activity of warm-sensitive and temperature-insensitive neurons in the medial preoptic area in rats.

PubMed

Xu, Jian-Hui; Hou, Xiao-Yu; Tang, Yu; Luo, Rong; Zhang, Jie; Liu, Chang; Yang, Yong-Lu

2018-01-01

Arginine vasopressin (AVP) plays an important role in thermoregulation and antipyresis. We have demonstrated that AVP could change the spontaneous activity of thermosensitive and temperature insensitive neurons in the preoptic area. However, whether AVP influences the effects of prostaglandin E 2 (PGE 2 ) on the spontaneous activity of neurons in the medial preoptic area (MPO) remains unclear. Our experiment showed that PGE 2 decreased the spontaneous activity of warm-sensitive neurons, and increased that of low-slope temperature-insensitive neurons in the MPO. AVP attenuated the inhibitory effect of PGE 2 on warm-sensitive neurons, and reversed the excitatory effect of PGE 2 on low-slope temperature-insensitive neurons, demonstrating that AVP antagonized the effects of PGE 2 on the spontaneous activity of these neurons. The effect of AVP was suppressed by an AVP V 1a receptor antagonist, suggesting that V 1a receptor mediated the action of AVP. We also demonstrated that AVP attenuated the PGE 2 -induced decrease in the prepotential's rate of rise in warm-sensitive neurons and the PGE 2 -induced increase in that in low-slope temperature-insensitive neurons through the V 1a receptor. Together, these data indicated that AVP antagonized the PGE 2 -induced change in the spontaneous activity of warm-sensitive and low-slope temperature-insensitive neurons in the MPO partly by reducing the PGE 2 -induced change in the prepotential of these neurons in a V 1a receptor-dependent manner. Copyright © 2017 Elsevier B.V. All rights reserved.

Mobile Learning for Teacher Professional Learning: Benefits, Obstacles and Issues

ERIC Educational Resources Information Center

Aubusson, Peter; Schuck, Sandy; Burden, Kevin

2009-01-01

This paper reflects on the role of mobile learning in teachers' professional learning. It argues that effective professional learning requires reflection and collaboration and that mobile learning is ideally suited to allow reflection-in-action and to capture the spontaneity of learning moments. The paper also argues for the value of…

Stages Identified in University Students' Behavior Using Mathematical Definitions

ERIC Educational Resources Information Center

Holguín, Valeria Aguirre

2016-01-01

This paper reports and describes some of the observations and conclusions drawn from a study developed to find information on undergraduate students' spontaneous actions and reactions to mathematical definitions that are new to them. There were 23 participants from a transition-to-proof course. They were interviewed individually on a particular…

Cholinergic Interneurons Underlie Spontaneous Dopamine Release in Nucleus Accumbens

PubMed Central

2017-01-01

The release of dopamine from terminals in the NAc is regulated by a number of factors, including voltage-gated ion channels, D2-autoreceptors, and nAChRs. Cholinergic interneurons (CINs) drive dopamine release through activation of nAChRs on dopamine terminals. Using cyclic voltammetry in mouse brain slices, nAChR-dependent spontaneous dopamine transients and the mechanisms underlying the origin were examined in the NAc. Spontaneous events were infrequent (0.3 per minute), but the rate and amplitude were increased after blocking Kv channels with 4-aminopyridine. Although the firing frequency of CINs was increased by blocking glutamate reuptake with TBOA and the Sk blocker apamin, only 4-aminopyridine increased the frequency of dopamine transients. In contrast, inhibition of CIN firing with the μ/δ selective opioid [Met5]enkephalin (1 μm) decreased spontaneous dopamine transients. Cocaine increased the rate and amplitude of dopamine transients, suggesting that the activity of the dopamine transporter limits the detection of these events. In the presence of cocaine, the rate of spontaneous dopamine transients was further increased after blocking D2-autoreceptors. Blockade of muscarinic receptors had no effect on evoked dopamine release, suggesting that feedback inhibition of acetylcholine release was not involved. Thus, although spontaneous dopamine transients are reliant on nAChRs, the frequency was not strictly governed by the activity of CINs. The increase in frequency of spontaneous dopamine transients induced by cocaine was not due to an increase in cholinergic tone and is likely a product of an increase in detection resulting from decreased dopamine reuptake. SIGNIFICANCE STATEMENT The actions of dopamine in the NAc are thought to be responsible for endogenous reward and the reinforcing properties of drugs of abuse, such as psychostimulants. The present work examines the mechanisms underlying nAChR-induced spontaneous dopamine release. This study demonstrates that spontaneous dopamine release is (1) dependent of the activation of nicotinic receptors, (2) independent on the spontaneous activity of cholinergic interneurons, and (3) that cocaine increased the detection of dopamine transients by prolonging the presence and increasing the diffusion of dopamine in the extracellular space. The release of acetylcholine is therefore responsible for spontaneous dopamine transients, and cocaine augments dopamine tone without altering activity of cholinergic interneurons. PMID:28115487

The Double-edged Sword of Pedagogy: Instruction limits spontaneous exploration and discovery

PubMed Central

Shafto, Patrick; Gweon, Hyowon; Goodman, Noah D.; Spelke, Elizabeth; Schulz, Laura

2012-01-01

Motivated by computational analyses, we look at how teaching affects exploration and discovery. In Experiment 1, we investigated children’s exploratory play after an adult pedagogically demonstrated a function of a toy, after an interrupted pedagogical demonstration, after a naïve adult demonstrated the function, and at baseline. Preschoolers in the pedagogical condition focused almost exclusively on the target function; by contrast, children in the other conditions explored broadly. In Experiment 2, we show that children restrict their exploration both after direct instruction to themselves and after overhearing direct instruction given to another child; they do not show this constraint after observing direct instruction given to an adult or after observing a non-pedagogical intentional action. We discuss these findings as the result of rational inductive biases. In pedagogical contexts, a teacher’s failure to provide evidence for additional functions provides evidence for their absence; such contexts generalize from child to child (because children are likely to have comparable states of knowledge) but not from adult to child. Thus, pedagogy promotes efficient learning but at a cost: children are less likely to perform potentially irrelevant actions but also less likely to discover novel information. PMID:21216395

The double-edged sword of pedagogy: Instruction limits spontaneous exploration and discovery.

PubMed

Bonawitz, Elizabeth; Shafto, Patrick; Gweon, Hyowon; Goodman, Noah D; Spelke, Elizabeth; Schulz, Laura

2011-09-01

Motivated by computational analyses, we look at how teaching affects exploration and discovery. In Experiment 1, we investigated children's exploratory play after an adult pedagogically demonstrated a function of a toy, after an interrupted pedagogical demonstration, after a naïve adult demonstrated the function, and at baseline. Preschoolers in the pedagogical condition focused almost exclusively on the target function; by contrast, children in the other conditions explored broadly. In Experiment 2, we show that children restrict their exploration both after direct instruction to themselves and after overhearing direct instruction given to another child; they do not show this constraint after observing direct instruction given to an adult or after observing a non-pedagogical intentional action. We discuss these findings as the result of rational inductive biases. In pedagogical contexts, a teacher's failure to provide evidence for additional functions provides evidence for their absence; such contexts generalize from child to child (because children are likely to have comparable states of knowledge) but not from adult to child. Thus, pedagogy promotes efficient learning but at a cost: children are less likely to perform potentially irrelevant actions but also less likely to discover novel information. Copyright © 2010. Published by Elsevier B.V.

INTERPRETING SPONTANEOUS RENAL LESIONS IN SAFETY AND RISK ASSESSMENT

EPA Science Inventory

Interpreting Spontaneous Renal Lesions in Safety and Risk Assessment
Douglas C. Wolf, D.V.M., Ph.D.

Introduction

Risk assessment is a process whereby the potential adverse health effects from exposure to a xenobiotic are predicted after evaluation of the availab...

Spontaneous dissection of the internal carotid artery manifesting as pain in an endodontically treated molar.

PubMed

Roz, Tamar M; Schiffman, Leonard E; Schlossberg, Sharon

2005-11-01

Dental pain is a common occurrence, whereas spontaneous dissection of an internal carotid artery is rare. The authors describe a patient who experienced a spontaneous dissection of an internal carotid artery that manifested initially as dental pain in an endodontically treated molar. It is important for dental practitioners to be familiar with unusual causes of dental pain. In this case in which the cause of dental pain was uncommon, the authors referred the patient appropriately, thus avoiding potentially serious complications.

Wide-field in vivo neocortical calcium dye imaging using a convection-enhanced loading technique combined with simultaneous multiwavelength imaging of voltage-sensitive dyes and hemodynamic signals

PubMed Central

Ma, Hongtao; Harris, Samuel; Rahmani, Redi; Lacefield, Clay O.; Zhao, Mingrui; Daniel, Andy G. S.; Zhou, Zhiping; Bruno, Randy M.; Berwick, Jason; Schwartz, Theodore H.

2014-01-01

Abstract. In vivo calcium imaging is an incredibly powerful technique that provides simultaneous information on fast neuronal events, such as action potentials and subthreshold synaptic activity, as well as slower events that occur in the glia and surrounding neuropil. Bulk-loading methods that involve multiple injections can be used for single-cell as well as wide-field imaging studies. However, multiple injections result in inhomogeneous loading as well as multiple sites of potential cortical injury. We used convection-enhanced delivery to create smooth, continuous loading of a large area of the cortical surface through a solitary injection site and demonstrated the efficacy of the technique using confocal microscopy imaging of single cells and physiological responses to single-trial events of spontaneous activity, somatosensory-evoked potentials, and epileptiform events. Combinations of calcium imaging with voltage-sensitive dye and intrinsic signal imaging demonstrate the utility of this technique in neurovascular coupling investigations. Convection-enhanced loading of calcium dyes may be a useful technique to advance the study of cortical processing when widespread loading of a wide-field imaging is required. PMID:25525611

Wide-field in vivo neocortical calcium dye imaging using a convection-enhanced loading technique combined with simultaneous multiwavelength imaging of voltage-sensitive dyes and hemodynamic signals.

PubMed

Ma, Hongtao; Harris, Samuel; Rahmani, Redi; Lacefield, Clay O; Zhao, Mingrui; Daniel, Andy G S; Zhou, Zhiping; Bruno, Randy M; Berwick, Jason; Schwartz, Theodore H

2014-07-24

In vivo calcium imaging is an incredibly powerful technique that provides simultaneous information on fast neuronal events, such as action potentials and subthreshold synaptic activity, as well as slower events that occur in the glia and surrounding neuropil. Bulk-loading methods that involve multiple injections can be used for single-cell as well as wide-field imaging studies. However, multiple injections result in inhomogeneous loading as well as multiple sites of potential cortical injury. We used convection-enhanced delivery to create smooth, continuous loading of a large area of the cortical surface through a solitary injection site and demonstrated the efficacy of the technique using confocal microscopy imaging of single cells and physiological responses to single-trial events of spontaneous activity, somatosensory-evoked potentials, and epileptiform events. Combinations of calcium imaging with voltage-sensitive dye and intrinsic signal imaging demonstrate the utility of this technique in neurovascular coupling investigations. Convection-enhanced loading of calcium dyes may be a useful technique to advance the study of cortical processing when widespread loading of a wide-field imaging is required.

Carbachol-Induced Reduction in the Activity of Adult Male Zebra Finch RA Projection Neurons.

PubMed

Meng, Wei; Wang, Song-Hua; Li, Dong-Feng

2016-01-01

Cholinergic mechanism is involved in motor behavior. In songbirds, the robust nucleus of the arcopallium (RA) is a song premotor nucleus in the pallium and receives cholinergic inputs from the basal forebrain. The activity of projection neurons in RA determines song motor behavior. Although many evidences suggest that cholinergic system is implicated in song production, the cholinergic modulation of RA is not clear until now. In the present study, the electrophysiological effects of carbachol, a nonselective cholinergic receptor agonist, were investigated on the RA projection neurons of adult male zebra finches through whole-cell patch-clamp techniques in vitro. Our results show that carbachol produced a significant decrease in the spontaneous and evoked action potential (AP) firing frequency of RA projection neurons, accompanying a hyperpolarization of the membrane potential, an increase in the evoked AP latency, afterhyperpolarization (AHP) peak amplitude, and AHP time to peak, and a decrease in the membrane input resistance, membrane time constant, and membrane capacitance. These results indicate that carbachol reduces the activity of RA projection neurons by hyperpolarizing the resting membrane potential and increasing the AHP and the membrane conductance, suggesting that the cholinergic modulation of RA may play an important role in song production.

Changes in intrinsic excitability of ganglion cells in degenerated retinas of RCS rats

PubMed Central

Ren, Yi-Ming; Weng, Chuan-Huang; Zhao, Cong-Jian; Yin, Zheng-Qin

2018-01-01

AIM To evaluate the intrinsic excitability of retinal ganglion cells (RGCs) in degenerated retinas. METHODS The intrinsic excitability of various morphologically defined RGC types using a combination of patch-clamp recording and the Lucifer yellow tracer in retinal whole-mount preparations harvested from Royal College of Surgeons (RCS) rats, a common retinitis pigmentosa (RP) model, in a relatively late stage of retinal degeneration (P90) were investigated. Several parameters of RGC morphologies and action potentials (APs) were measured and compared to those of non-dystrophic control rats, including dendritic stratification, dendritic field diameter, peak amplitude, half width, resting membrane potential, AP threshold, depolarization to threshold, and firing rates. RESULTS Compared with non-dystrophic control RGCs, more depolarizations were required to reach the AP threshold in RCS RGCs with low spontaneous spike rates and in RCS OFF cells (especially A2o cells), and RCS RGCs maintained their dendritic morphologies, resting membrane potentials and capabilities to generate APs. CONCLUSION RGCs are relatively well preserved morphologically and functionally, and some cells are more susceptible to decreased excitability during retinal degeneration. These findings provide valuable considerations for optimizing RP therapeutic strategies. PMID:29862172

Kv1.1 knock-in ataxic mice exhibit spontaneous myokymic activity exacerbated by fatigue, ischemia and low temperature.

PubMed

Brunetti, Orazio; Imbrici, Paola; Botti, Fabio Massimo; Pettorossi, Vito Enrico; D'Adamo, Maria Cristina; Valentino, Mario; Zammit, Christian; Mora, Marina; Gibertini, Sara; Di Giovanni, Giuseppe; Muscat, Richard; Pessia, Mauro

2012-09-01

Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder characterized by myokymia and attacks of ataxic gait often precipitated by stress. Several genetic mutations have been identified in the Shaker-like K(+) channel Kv1.1 (KCNA1) of EA1 individuals, including V408A, which result in remarkable channel dysfunction. By inserting the heterozygous V408A, mutation in one Kv1.1 allele, a mouse model of EA1 has been generated (Kv1.1(V408A/+)). Here, we investigated the neuromuscular transmission of Kv1.1(V408A/+) ataxic mice and their susceptibility to physiologically relevant stressors. By using in vivo preparations of lateral gastrocnemius (LG) nerve-muscle from Kv1.1(+/+) and Kv1.1(V408A/+) mice, we show that the mutant animals exhibit spontaneous myokymic discharges consisting of repeated singlets, duplets or multiplets, despite motor nerve axotomy. Two-photon laser scanning microscopy from the motor nerve, ex vivo, revealed spontaneous Ca(2+) signals that occurred abnormally only in preparations dissected from Kv1.1(V408A/+) mice. Spontaneous bursting activity, as well as that evoked by sciatic nerve stimulation, was exacerbated by muscle fatigue, ischemia and low temperatures. These stressors also increased the amplitude of compound muscle action potential. Such abnormal neuromuscular transmission did not alter fiber type composition, neuromuscular junction and vascularization of LG muscle, analyzed by light and electron microscopy. Taken together these findings provide direct evidence that identifies the motor nerve as an important generator of myokymic activity, that dysfunction of Kv1.1 channels alters Ca(2+) homeostasis in motor axons, and also strongly suggest that muscle fatigue contributes more than PNS fatigue to exacerbate the myokymia/neuromyotonia phenotype. More broadly, this study points out that juxtaparanodal K(+) channels composed of Kv1.1 subunits exert an important role in dampening the excitability of motor nerve axons during fatigue or ischemic insult. Copyright © 2012 Elsevier Inc. All rights reserved.

Spontaneous Fission

DOE R&D Accomplishments Database

Segre, Emilio

1950-11-22

The first attempt to discover spontaneous fission in uranium was made by [Willard] Libby, who, however, failed to detect it on account of the smallness of effect. In 1940, [K. A.] Petrzhak and [G. N.] Flerov, using more sensitive methods, discovered spontaneous fission in uranium and gave some rough estimates of the spontaneous fission decay constant of this substance. Subsequently, extensive experimental work on the subject has been performed by several investigators and will be quoted in the various sections. [N.] Bohr and [A.] Wheeler have given a theory of the effect based on the usual ideas of penetration of potential barriers. On this project spontaneous fission has been studied for the past several years in an effort to obtain a complete picture of the phenomenon. For this purpose the spontaneous fission decay constants {lambda} have been measured for separated isotopes of the heavy elements wherever possible. Moreover, the number {nu} of neutrons emitted per fission has been measured wherever feasible, and other characteristics of the spontaneous fission process have been studied. This report summarizes the spontaneous fission work done at Los Alamos up to January 1, 1945. A chronological record of the work is contained in the Los Alamos monthly reports.

Disruption of communication between peripheral and central trigeminovascular neurons mediates the antimigraine action of 5HT1B/1D receptor agonists

PubMed Central

Levy, Dan; Jakubowski, Moshe; Burstein, Rami

2004-01-01

Triptans are 5HT1B/1D receptor agonists commonly prescribed for migraine headache. Although originally designed to constrict dilated intracranial blood vessels, the mechanism and site of action by which triptans abort the migraine pain remain unknown. We showed recently that sensitization of peripheral and central trigeminovascular neurons plays an important role in the pathophysiology of migraine pain. Here we examined whether the drug sumatriptan can prevent and/or suppress peripheral and central sensitization by using single-unit recording in our animal model of intracranial pain. We found that sumatriptan effectively prevented the induction of sensitization (i.e., increased spontaneous firing; increased neuronal sensitivity to intracranial mechanical stimuli) in central trigeminovascular neurons (recorded in the dorsal horn), but not in peripheral trigeminovascular neurons (recorded in the trigeminal ganglion). After sensitization was established in both types of neuron, sumatriptan effectively normalized intracranial mechanical sensitivity of central neurons, but failed to reverse such hypersensitivity in peripheral neurons. In both the peripheral and central neurons, the drug failed to attenuate the increased spontaneous activity established during sensitization. These results suggest that neither peripheral nor central trigeminovascular neurons are directly inhibited by sumatriptan. Rather, triptan action appears to be exerted through presynaptic 5HT1B/1D receptors in the dorsal horn to block synaptic transmission between axon terminals of the peripheral trigeminovascular neurons and cell bodies of their central counterparts. We therefore suggest that the analgesic action of triptan can be attained specifically in the absence, but not in the presence, of central sensitization. PMID:15016917

Disruption of communication between peripheral and central trigeminovascular neurons mediates the antimigraine action of 5HT 1B/1D receptor agonists.

PubMed

Levy, Dan; Jakubowski, Moshe; Burstein, Rami

2004-03-23

Triptans are 5HT(1B/1D) receptor agonists commonly prescribed for migraine headache. Although originally designed to constrict dilated intracranial blood vessels, the mechanism and site of action by which triptans abort the migraine pain remain unknown. We showed recently that sensitization of peripheral and central trigeminovascular neurons plays an important role in the pathophysiology of migraine pain. Here we examined whether the drug sumatriptan can prevent and/or suppress peripheral and central sensitization by using single-unit recording in our animal model of intracranial pain. We found that sumatriptan effectively prevented the induction of sensitization (i.e., increased spontaneous firing; increased neuronal sensitivity to intracranial mechanical stimuli) in central trigeminovascular neurons (recorded in the dorsal horn), but not in peripheral trigeminovascular neurons (recorded in the trigeminal ganglion). After sensitization was established in both types of neuron, sumatriptan effectively normalized intracranial mechanical sensitivity of central neurons, but failed to reverse such hypersensitivity in peripheral neurons. In both the peripheral and central neurons, the drug failed to attenuate the increased spontaneous activity established during sensitization. These results suggest that neither peripheral nor central trigeminovascular neurons are directly inhibited by sumatriptan. Rather, triptan action appears to be exerted through presynaptic 5HT(1B/1D) receptors in the dorsal horn to block synaptic transmission between axon terminals of the peripheral trigeminovascular neurons and cell bodies of their central counterparts. We therefore suggest that the analgesic action of triptan can be attained specifically in the absence, but not in the presence, of central sensitization.

Stimulation of GABA-Induced Ca2+ Influx Enhances Maturation of Human Induced Pluripotent Stem Cell-Derived Neurons

PubMed Central

Rushton, David J.; Mattis, Virginia B.; Svendsen, Clive N.; Allen, Nicholas D.; Kemp, Paul J.

2013-01-01

Optimal use of patient-derived, induced pluripotent stem cells for modeling neuronal diseases is crucially dependent upon the proper physiological maturation of derived neurons. As a strategy to develop defined differentiation protocols that optimize electrophysiological function, we investigated the role of Ca2+ channel regulation by astrocyte conditioned medium in neuronal maturation, using whole-cell patch clamp and Ca2+ imaging. Standard control medium supported basic differentiation of induced pluripotent stem cell-derived neurons, as assayed by the ability to fire simple, single, induced action potentials. In contrast, treatment with astrocyte conditioned medium elicited complex and spontaneous neuronal activity, often with rhythmic and biphasic characteristics. Such augmented spontaneous activity correlated with astrocyte conditioned medium-evoked hyperpolarization and was dependent upon regulated function of L-, N- and R-type Ca2+ channels. The requirement for astrocyte conditioned medium could be substituted by simply supplementing control differentiation medium with high Ca2+ or γ-amino butyric acid (GABA). Importantly, even in the absence of GABA signalling, opening Ca2+ channels directly using Bay K8644 was able to hyperpolarise neurons and enhance excitability, producing fully functional neurons. These data provide mechanistic insight into how secreted astrocyte factors control differentiation and, importantly, suggest that pharmacological modulation of Ca2+ channel function leads to the development of a defined protocol for improved maturation of induced pluripotent stem cell-derived neurons. PMID:24278369

Glucose rapidly induces different forms of excitatory synaptic plasticity in hypothalamic POMC neurons.

PubMed

Hu, Jun; Jiang, Lin; Low, Malcolm J; Rui, Liangyou

2014-01-01

Hypothalamic POMC neurons are required for glucose and energy homeostasis. POMC neurons have a wide synaptic connection with neurons both within and outside the hypothalamus, and their activity is controlled by a balance between excitatory and inhibitory synaptic inputs. Brain glucose-sensing plays an essential role in the maintenance of normal body weight and metabolism; however, the effect of glucose on synaptic transmission in POMC neurons is largely unknown. Here we identified three types of POMC neurons (EPSC(+), EPSC(-), and EPSC(+/-)) based on their glucose-regulated spontaneous excitatory postsynaptic currents (sEPSCs), using whole-cell patch-clamp recordings. Lowering extracellular glucose decreased the frequency of sEPSCs in EPSC(+) neurons, but increased it in EPSC(-) neurons. Unlike EPSC(+) and EPSC(-) neurons, EPSC(+/-) neurons displayed a bi-phasic sEPSC response to glucoprivation. In the first phase of glucoprivation, both the frequency and the amplitude of sEPSCs decreased, whereas in the second phase, they increased progressively to the levels above the baseline values. Accordingly, lowering glucose exerted a bi-phasic effect on spontaneous action potentials in EPSC(+/-) neurons. Glucoprivation decreased firing rates in the first phase, but increased them in the second phase. These data indicate that glucose induces distinct excitatory synaptic plasticity in different subpopulations of POMC neurons. This synaptic remodeling is likely to regulate the sensitivity of the melanocortin system to neuronal and hormonal signals.

Cerebellar Purkinje Cells Generate Highly Correlated Spontaneous Slow-Rate Fluctuations.

PubMed

Cao, Ying; Liu, Yu; Jaeger, Dieter; Heck, Detlef H

2017-01-01

Cerebellar Purkinje cells (PC) fire action potentials at high, sustained rates. Changes in spike rate that last a few tens of milliseconds encode sensory and behavioral events. Here we investigated spontaneous fluctuations of PC simple spike rate at a slow time scale of the order of 1 s. Simultaneous recordings from pairs of PCs that were aligned either along the sagittal or transversal axis of the cerebellar cortex revealed that simple spike rate fluctuations at the 1 s time scale were highly correlated. Each pair of PCs had either a predominantly positive or negative slow-rate correlation, with negative correlations observed only in PC pairs aligned along the transversal axis. Slow-rate correlations were independent of faster rate changes that were correlated with fluid licking behavior. Simultaneous recordings from PCs and cerebellar nuclear (CN) neurons showed that slow-rate fluctuations in PC and CN activity were also highly correlated, but their correlations continually alternated between periods of positive and negative correlation. The functional significance of this new aspect of cerebellar spike activity remains to be determined. Correlated slow-rate fluctuations seem too slow to be involved in the real-time control of ongoing behavior. However, slow-rate fluctuations of PCs converging on the same CN neuron are likely to modulate the excitability of the CN neuron, thus introduce a possible slow modulation of cerebellar output activity.

Enhanced contractility of the rat stomach during suppression of angiotensin converting enzyme by captopril in vitro.

PubMed Central

Rani, R.; Rao, K. S.

1991-01-01

1. Intragastric pressure (IGP) was used as an index, of the effect of serosal application of captopril (SQ 14,225; D-3-mercapto-2-methylpropanoyl-L-proline) on the contractility of rat stomach in vitro. 2. Captopril, at concentrations greater than 0.3 microM, enhanced the spontaneous gastric motility (GM) in a concentration-dependent manner whereas concentrations less than 0.3 microM selectively potentiated 4 nM bradykinin (BK)-evoked gastric contractions without significantly affecting the spontaneous GM. 3. The kallikrein inhibitor, aprotinin (100 u ml-1), markedly antagonized the enhanced GM to 1.4 microM captopril and BK (4 nM)-evoked contractions, without affecting the contractions evoked by angiotensin 1 (10 nM) and acetylcholine (0.4 microM). The angiotensin II antagonist, saralasin (50 microM) failed to mimic aprotinin. 4. The enhanced GM to captopril was markedly inhibited by tetrodotoxin (1 microM), and partially inhibited by atropine (1 microM). 5. These results indicate that in vitro, captopril (greater than 0.3 microM) enhances gastric contractility through kininase/ACE inhibitory action, presumably by increasing the concentration of undegraded tissue kinins and substance P. This motor response seems to be predominantly due to activation of the cholinergic neurones but non-cholinergic excitatory neurones are also involved. PMID:1713107

Developmental profile of localized spontaneous Ca2+ release events in the dendrites of rat hippocampal pyramidal neurons

PubMed Central

Miyazaki, Kenichi; Manita, Satoshi; Ross, William N.

2012-01-01

Summary Recent experiments demonstrate that localized spontaneous Ca2+ release events can be detected in the dendrites of pyramidal cells in the hippocampus and other neurons (J. Neurosci. 29:7833-7845, 2009). These events have some properties that resemble ryanodine receptor mediated “sparks” in myocytes, and some that resemble IP3 receptor mediated “puffs” in oocytes. They can be detected in the dendrites of rats of all tested ages between P3 and P80 (with sparser sampling in older rats), suggesting that they serve a general signaling function and are not just important in development. However, in younger rats the amplitudes of the events are larger than the amplitudes in older animals and almost as large as the amplitudes of Ca2+ signals from backpropagating action potentials (bAPs). The rise time of the event signal is fast at all ages and is comparable to the rise time of the bAP fluorescence signal at the same dendritic location. The decay time is slower in younger animals, primarily because of weaker Ca2+ extrusion mechanisms at that age. Diffusion away from a brief localized source is the major determinant of decay at all ages. A simple computational model closely simulates these events with extrusion rate the only age dependent variable. PMID:22951184

Distinct Physiological Effects of Dopamine D4 Receptors on Prefrontal Cortical Pyramidal Neurons and Fast-Spiking Interneurons

PubMed Central

Zhong, Ping; Yan, Zhen

2016-01-01

Dopamine D4 receptor (D4R), which is strongly linked to neuropsychiatric disorders, such as attention-deficit hyperactivity disorder and schizophrenia, is highly expressed in pyramidal neurons and GABAergic interneurons in prefrontal cortex (PFC). In this study, we examined the impact of D4R on the excitability of these 2 neuronal populations. We found that D4R activation decreased the frequency of spontaneous action potentials (sAPs) in PFC pyramidal neurons, whereas it induced a transient increase followed by a decrease of sAP frequency in PFC parvalbumin-positive (PV+) interneurons. D4R activation also induced distinct effects in both types of PFC neurons on spontaneous excitatory and inhibitory postsynaptic currents, which drive the generation of sAP. Moreover, dopamine substantially decreased sAP frequency in PFC pyramidal neurons, but markedly increased sAP frequency in PV+ interneurons, and both effects were partially mediated by D4R activation. In the phencyclidine model of schizophrenia, the decreasing effect of D4R on sAP frequency in both types of PFC neurons was attenuated, whereas the increasing effect of D4R on sAP in PV+ interneurons was intact. These results suggest that D4R activation elicits distinct effects on synaptically driven excitability in PFC projection neurons versus fast-spiking interneurons, which are differentially altered in neuropsychiatric disorder-related conditions. PMID:25146372

Volition and conflict in human medial frontal cortex.

PubMed

Nachev, Parashkev; Rees, Geraint; Parton, Andrew; Kennard, Christopher; Husain, Masud

2005-01-26

Controversy surrounds the role of human medial frontal cortex in controlling actions. Although damage to this area leads to severe difficulties in spontaneously initiating actions, the precise mechanisms underlying such "volitional" deficits remain to be established. Previous studies have implicated the medial frontal cortex in conflict monitoring and the control of voluntary action, suggesting that these key processes are functionally related or share neural substrates. Here, we combine a novel behavioral paradigm with functional imaging of the oculomotor system to reveal, for the first time, a functional subdivision of the pre-supplementary motor area (pre-SMA) into anatomically distinct areas that respond exclusively to either volition or conflict. We also demonstrate that activity in the supplementary eye field (SEF) distinguishes between success and failure in changing voluntary action plans during conflict, suggesting a role for the SEF in implementing the resolution of conflicting actions. We propose a functional architecture of human medial frontal cortex that incorporates the generation of action plans and the resolution of conflict.

Interhemispheric correlations of slow spontaneous neuronal fluctuations revealed in human sensory cortex

PubMed Central

Nir, Yuval; Mukamel, Roy; Dinstein, Ilan; Privman, Eran; Harel, Michal; Fisch, Lior; Gelbard-Sagiv, Hagar; Kipervasser, Svetlana; Andelman, Fani; Neufeld, Miri Y; Kramer, Uri; Arieli, Amos; Fried, Itzhak; Malach, Rafael

2009-01-01

Animal studies have shown robust electrophysiological activity in the sensory cortex in the absence of stimuli or tasks. Similarly, recent human functional magnetic resonance imaging (fMRI) revealed widespread, spontaneously emerging cortical fluctuations. However, it is unknown what neuronal dynamics underlie this spontaneous activity in the human brain. Here we studied this issue by combining bilateral single-unit, local field potentials (LFPs) and intracranial electrocorticography (ECoG) recordings in individuals undergoing clinical monitoring. We found slow (<0.1 Hz, following 1/f-like profiles) spontaneous fluctuations of neuronal activity with significant interhemispheric correlations. These fluctuations were evident mainly in neuronal firing rates and in gamma (40–100 Hz) LFP power modulations. Notably, the interhemispheric correlations were enhanced during rapid eye movement and stage 2 sleep. Multiple intracranial ECoG recordings revealed clear selectivity for functional networks in the spontaneous gamma LFP power modulations. Our results point to slow spontaneous modulations in firing rate and gamma LFP as the likely correlates of spontaneous fMRI fluctuations in the human sensory cortex. PMID:19160509

Spontaneous Swallow Frequency Compared with Clinical Screening in the Identification of Dysphagia in Acute Stroke

PubMed Central

Crary, Michael A.; Carnaby, Giselle D.; Sia, Isaac

2017-01-01

Background The aim of this study was to compare spontaneous swallow frequency analysis (SFA) with clinical screening protocols for identification of dysphagia in acute stroke. Methods In all, 62 patients with acute stroke were evaluated for spontaneous swallow frequency rates using a validated acoustic analysis technique. Independent of SFA, these same patients received a routine nurse-administered clinical dysphagia screening as part of standard stroke care. Both screening tools were compared against a validated clinical assessment of dysphagia for acute stroke. In addition, psychometric properties of SFA were compared against published, validated clinical screening protocols. Results Spontaneous SFA differentiates patients with versus without dysphagia after acute stroke. Using a previously identified cut point based on swallows per minute, spontaneous SFA demonstrated superior ability to identify dysphagia cases compared with a nurse-administered clinical screening tool. In addition, spontaneous SFA demonstrated equal or superior psychometric properties to 4 validated, published clinical dysphagia screening tools. Conclusions Spontaneous SFA has high potential to identify dysphagia in acute stroke with psychometric properties equal or superior to clinical screening protocols. PMID:25088166

Spontaneous swallow frequency compared with clinical screening in the identification of dysphagia in acute stroke.

PubMed

Crary, Michael A; Carnaby, Giselle D; Sia, Isaac

2014-09-01

The aim of this study was to compare spontaneous swallow frequency analysis (SFA) with clinical screening protocols for identification of dysphagia in acute stroke. In all, 62 patients with acute stroke were evaluated for spontaneous swallow frequency rates using a validated acoustic analysis technique. Independent of SFA, these same patients received a routine nurse-administered clinical dysphagia screening as part of standard stroke care. Both screening tools were compared against a validated clinical assessment of dysphagia for acute stroke. In addition, psychometric properties of SFA were compared against published, validated clinical screening protocols. Spontaneous SFA differentiates patients with versus without dysphagia after acute stroke. Using a previously identified cut point based on swallows per minute, spontaneous SFA demonstrated superior ability to identify dysphagia cases compared with a nurse-administered clinical screening tool. In addition, spontaneous SFA demonstrated equal or superior psychometric properties to 4 validated, published clinical dysphagia screening tools. Spontaneous SFA has high potential to identify dysphagia in acute stroke with psychometric properties equal or superior to clinical screening protocols. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Parents' rules about underage drinking: A qualitative study of why parents let teens drink

PubMed Central

Friese, Bettina; Grube, Joel W.; Moore, Roland S.; Jennings, Vanessa K.

2013-01-01

Results from a qualitative study with parents about underage drinking are presented. Semi-structured interviews (n=44) were conducted with parents of teens to investigate whether and why parents permit underage drinking. Parents had three primary reasons for allowing underage drinking: deliberate, spontaneous and harm reduction. Deliberate reasons included passing on knowledge about drinking responsibly and appreciating alcohol. Parents also spontaneously decided to let their teen drink. Some of these spontaneous situations involved feeling pressure from other adults to let their teen drink. Another reason was a desire to reduce potential harm. Parents feared that forbidding underage drinking would harm their relationship with their teen and potentially lead to drunk driving. Prevention efforts aimed at parents should take into account parents' motivations to let teens drink. PMID:25031481

Quantifying the Relationship between Curvature and Electric Potential in Lipid Bilayers.

PubMed

Bruhn, Dennis S; Lomholt, Michael A; Khandelia, Himanshu

2016-06-02

Cellular membranes mediate vital cellular processes by being subject to curvature and transmembrane electrical potentials. Here we build upon the existing theory for flexoelectricity in liquid crystals to quantify the coupling between lipid bilayer curvature and membrane potentials. Using molecular dynamics simulations, we show that headgroup dipole moments, the lateral pressure profile across the bilayer, and spontaneous curvature all systematically change with increasing membrane potentials. In particular, there is a linear dependence between the bending moment (the product of bending rigidity and spontaneous curvature) and the applied membrane potentials. We show that biologically relevant membrane potentials can induce biologically relevant curvatures corresponding to radii of around 500 nm. The implications of flexoelectricity in lipid bilayers are thus likely to be of considerable consequence both in biology and in model lipid bilayer systems.

You and me: Investigating the role of self-evaluative emotion in preschool prosociality.

PubMed

Ross, Josephine

2017-03-01

Self-evaluative emotions depend on internalized social standards and motivate social action. However, there is a lack of empirical research documenting the impact of self-evaluative emotion on 3- and 4-year-olds' prosociality. Extant research relates children's experiences of guilt to empathetic concern and making amends. However, the relationship between guilt and both concern and making amends is potentially reductive. Empathetic concern involves similar bodily expressions to guilt, and amend making is used to distinguish guilt from shame in children. This is the first study to relate the development of both positive and negative self-evaluative emotions to empathetic concern and prosocial choice (making amends and spontaneous help). Results confirm that the broad capacity for self-evaluative emotion is established during the preschool years and relates to empathetic concern. Moreover, these social emotions can be used to predict prosocial choice. Making amends was best predicted by empathetic concern and by children's responses to achievement (pride following success and lack of shame following failure). Alongside moral pride, pride in response to achievement and resilience to shame was also the best predictor of spontaneous help. The data support the idea that young children's prosocial choices may be partially driven by the affective drive to maintain an "ideal" self. Psychologists have emphasized that in order to be adaptive, self-evaluative emotion should be guilt oriented rather than shame oriented. However, the adaptive role of pride has been neglected. We call on future research to redress the focus on negative self-evaluation in moral development and further explore the prosocial potential of pride. Copyright © 2016 Elsevier Inc. All rights reserved.

Spontaneous release from mossy fiber terminals inhibits Ni2+-sensitive T-type Ca2+ channels of CA3 pyramidal neurons in the rat organotypic hippocampal slice.

PubMed

Reid, Christopher A; Xu, Shenghong; Williams, David A

2008-01-01

Mossy fibers (axons arising from dentate granule cells) form large synaptic contacts exclusively onto the proximal apical dendrites of CA3 pyramidal neurons. They can generate large synaptic currents that occur in close proximity to the soma. These properties mean that active conductance in the proximal apical dendrite could have a disproportionate influence on CA3 pyramidal neuron excitability. Ni(2+)-sensitive T-type Ca(2+) channels are important modulators of dendritic excitability. Here, we use an optical approach to determine the contribution of Ni(2+) (100 microM)-sensitive Ca(2+) channels to action potential (AP) elicited Ca(2+) flux in the soma, proximal apical and distal apical dendrites. At resting membrane potentials Ni(2+)-sensitive Ca(2+) channels do not contribute to the Ca(2+) signal in the proximal apical dendrite, but do contribute in the other cell regions. Spontaneous release from mossy fiber terminals acting on 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive postsynaptic channels underlies a tonic inhibition of Ni(2+)-sensitive channels. Chelating Zn(2+) with CaEDTA blocks CNQX-sensitive changes in Ca(2+) flux implicating a mechanistic role of this ion in T-type Ca(2+) channel block. To test if this inhibition influenced excitability, progressively larger depolarizing pulses were delivered to CA3 pyramidal neurons. CNQX significantly reduced the size of the depolarizing step required to generate APs and increased the absolute number of APs per depolarizing step. This change in AP firing was completely reversed by the addition of Ni(2+). This mechanism may reduce the impact of T-type Ca(2+) channels in a region where large synaptic events are common.

Renal mitochondrial dysfunction in spontaneously hypertensive rats is attenuated by losartan but not by amlodipine.

PubMed

de Cavanagh, Elena M V; Toblli, Jorge E; Ferder, León; Piotrkowski, Bárbara; Stella, Inés; Inserra, Felipe

2006-06-01

Mitochondrial dysfunction is associated with cardiovascular damage; however, data on a possible association with kidney damage are scarce. Here, we aimed at investigating whether 1) kidney impairment is related to mitochondrial dysfunction; and 2) ANG II blockade, compared with Ca2+ channel blockade, can reverse potential mitochondrial changes in hypertension. Eight-week-old male spontaneously hypertensive rats (SHR) received water containing losartan (40 mg.kg-1.day-1, SHR+Los), amlodipine (3 mg.kg-1.day-1, SHR+Amlo), or no additions (SHR) for 6 mo. Wistar-Kyoto rats (WKY) were normotensive controls. Glomerular and tubulointerstitial damage, systolic blood pressure, and proteinuria were higher, and creatinine clearance was lower in SHR vs. SHR+Los and WKY. In SHR+Amlo, blood pressure was similar to WKY, kidney function was similar to SHR, and renal lesions were lower than in SHR, but higher than in SHR+Los. In kidney mitochondria from SHR and SHR+Amlo, membrane potential, nitric oxide synthase, manganese-superoxide dismutase and cytochrome oxidase activities, and uncoupling protein-2 content were lower than in SHR+Los and WKY. In SHR and SHR+Amlo, mitochondrial H2O2 production was higher than in SHR+Los and WKY. Renal glutathione content was lower in SHR+Amlo relative to SHR, SHR+Los, and WKY. In SHR and SHR+Amlo, glutathione was relatively more oxidized than in SHR+Los and WKY. Tubulointerstitial alpha-smooth muscle actin labeling was inversely related to manganese-superoxide dismutase activity and uncoupling protein-2 content. These findings suggest that oxidant stress is associated with renal mitochondrial dysfunction in SHR. The mitochondrial-antioxidant actions of losartan may be an additional or alternative way to explain some of the beneficial effects of AT1-receptor antagonists.

Histamine H3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons.

PubMed

Varaschin, Rafael Koerich; Osterstock, Guillaume; Ducrot, Charles; Leino, Sakari; Bourque, Marie-Josée; Prado, Marco A M; Prado, Vania Ferreira; Salminen, Outi; Rannanpää Née Nuutinen, Saara; Trudeau, Louis-Eric

2018-04-15

Histamine H 3 receptors are widely distributed G i -coupled receptors whose activation reduces neuronal activity and inhibits release of numerous neurotransmitters. Although these receptors are abundantly expressed in the striatum, their modulatory role on activity-dependent dopamine release is not well understood. Here, we observed that histamine H 3 receptor activation indirectly diminishes dopamine overflow in the ventral striatum by reducing cholinergic interneuron activity. Acute brain slices from C57BL/6 or channelrhodopsin-2-transfected DAT-cre mice were obtained, and dopamine transients evoked either electrically or optogenetically were measured by fast-scan cyclic voltammetry. The H 3 agonist α-methylhistamine significantly reduced electrically- evoked dopamine overflow, an effect blocked by the nicotinic acetylcholine receptor antagonist dihydro-β-erythroidine, suggesting involvement of cholinergic interneurons. None of the drug treatments targeting H 3 receptors affected optogenetically evoked dopamine overflow, indicating that direct H 3 -modulation of dopaminergic axons is unlikely. Next, we used qPCR and confirmed the expression of histamine H 3 receptor mRNA in cholinergic interneurons, both in ventral and dorsal striatum. Activation of H 3 receptors by α-methylhistamine reduced spontaneous firing of cholinergic interneurons in the ventral, but not in the dorsal striatum. Resting membrane potential and number of spontaneous action potentials in ventral-striatal cholinergic interneurons were significantly reduced by α-methylhistamine. Acetylcholine release from isolated striatal synaptosomes, however, was not altered by α-methylhistamine. Together, these results indicate that histamine H 3 receptors are important modulators of dopamine release, specifically in the ventral striatum, and that they do so by decreasing the firing rate of cholinergic neurons and, consequently, reducing cholinergic tone on dopaminergic axons. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

An ionotropic but not a metabotropic glutamate agonist potentiates the pharmacological effects of olanzapine in the rat.

PubMed

Dall'Olio, Rossella; Rimondini, Roberto; Locchi, Federica; Voltattorni, Manuela; Gandolfi, Ottavio

2005-12-01

This study aimed to evaluate the possible potentiating action of ionotropic or metabotropic (metabotropic glutamate receptor type 5) glutamate agonists on pharmacological effects induced in rats by the atypical antipsychotic olanzapine. The administration of doses of olanzapine, which did not affect spontaneous motility, inhibited behaviors induced by the selective stimulation of 5HT(2A) and D(2) receptors. In particular, 0.03 or 0.06 mg/kg of olanzapine was sufficient to reduce, respectively, head shakes induced by the 5HT(2A) agonist 1-2,5-dimethoxy-4-iodophenyl-2-aminopropane (1 mg/kg) or hypermotility elicited by the D(2) stimulant quinpirole (0.15 mg/kg). Behavioral responses to a D(1)/D(2) agonist (apomorphine-induced stereotypies) were inhibited by doses of olanzapine that also influenced spontaneous behavior. The concomitant administration of D-cycloserine, an agonist at the glycine site on the N-methyl-D-aspartate receptor complex, given at a dose (3 mg/kg) that did not affect behavior, increased the inhibitory effect of olanzapine on the responses produced by 5HT2A, D(2) and D(1)/D(2) receptor stimulation. The concomitant administration of 2-chloro-5-hydroxyphenylglycine, an agonist of metabotropic glutamate receptor type 5, increased the inhibitory effect of olanzapine on the behaviors induced by the stimulation of D(2), but not 5HT2A or D(1)/D(2) receptors. As the effect on the serotonergic system seems important for the unusual pharmacological profile of atypical antipsychotics, the present results suggest that N-methyl-D-aspartate, but not metabotropic glutamate receptor type 5 agonists could be seen as promising therapeutic agents for increasing the pharmacological effects of olanzapine.

Acute central effects of alarin on the regulation on energy homeostasis.

PubMed

Mikó, Alexandra; Füredi, Nóra; Tenk, Judit; Rostás, Ildikó; Soós, Szilvia; Solymár, Margit; Székely, Miklós; Balaskó, Márta; Brunner, Susanne M; Kofler, Barbara; Pétervári, Erika

2017-08-01

Hypothalamic neuropeptides influence the main components of energy balance: metabolic rate, food intake, body weight as well as body temperature, by exerting either an overall anabolic or catabolic effect. The contribution of alarin, the most recently discovered member of the galanin peptide family to the regulation of energy metabolism has been suggested. Our aim was to analyze the complex thermoregulatory and food intake-related effects of alarin in rats. Adult male Wistar rats received different doses of alarin (0.3; 1; 3 and 15μg corresponding approximately to 0.1, 0.33, 1, and 5 nmol, respectively) intracerebroventricularly. Regarding thermoregulatory analysis, oxygen consumption (indicating metabolic rate), core temperature and heat loss (assessed by tail skin temperature) were recorded in an Oxymax indirect calorimeter system complemented with thermocouples and Benchtop thermometer. In order to investigate potential prostaglandin-mediated mechanisms of the hyperthermic effect of alarin, effects of intraperitoneally applied non-selective (indomethacin, 2mg/kg) or selective cyclooxygenase inhibitor (COX-2 inhibitor meloxicam, 1; 2mg/kg) were tested. Effects of alarin on daytime and nighttime spontaneous food intake, as well as, 24-h fasting-induced re-feeding were recorded in an automated FeedScale system. Alarin increased oxygen consumption with simultaneous suppression of heat loss leading to a slow coordinated rise in core temperature. Both applied COX-inhibitors suppressed this action. Alarin failed to induce daytime food intake, but suppressed spontaneous nighttime and also fasting-induced re-feeding food intake. Alarin appears to elicit a slow anorexigenic and prostaglandin-mediated, fever-like hyperthermic response in rats. Such a combination would characterize a catabolic mediator. The potential involvement of alarin in sickness behavior may be assumed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lycopene Protects Against Spontaneous Ovarian Cancer Formation in Laying Hens.

PubMed

Sahin, Kazim; Yenice, Engin; Tuzcu, Mehmet; Orhan, Cemal; Mizrak, Cengizhan; Ozercan, Ibrahim H; Sahin, Nurhan; Yilmaz, Bahiddin; Bilir, Birdal; Ozpolat, Bulent; Kucuk, Omer

2018-03-01

Dietary intake of lycopene has been associated with a reduced risk of ovarian cancer, suggesting its chemopreventive potential against ovarian carcinogenesis. Lycopene's molecular mechanisms of action in ovarian cancer have not been fully understood. Therefore, in the present study, we investigated the effects of lycopene on the ovarian cancer formation using the laying hen model, a biologically relevant animal model of spontaneous ovarian carcinogenesis due to high incidence rates similar to humans. In this study, a total of 150 laying hens at age of 102 weeks were randomized into groups of 50: a control group (0 mg of lycopene per kg of diet) and two treatment groups (200 mg or 400 mg of lycopene per kg of diet, or ~26 and 52 mg/d/hen, respectively). At the end of 12 months, blood, ovarian tissues and tumors were collected. We observed that lycopene supplementation significantly reduced the overall ovarian tumor incidence ( P < 0.01) as well as the number and the size of the tumors ( P < 0.004 and P < 0.005, respectively). Lycopene also significantly decreased the rate of adenocarcinoma, including serous and mucinous subtypes ( P < 0.006). Moreover, we also found that the serum level of oxidative stress marker malondialdehyde was significantly lower in lycopene-fed hens compared to control birds ( P < 0.001). Molecular analysis of the ovarian tumors revealed that lycopene reduced the expression of NF-κB while increasing the expression of nuclear factor erythroid 2 and its major target protein, heme oxygenase 1. In addition, lycopene supplementation decreased the expression of STAT3 by inducing the protein inhibitor of activated STAT3 expression in the ovarian tissues. Taken together, our findings strongly support the potential of lycopene in the chemoprevention of ovarian cancer through antioxidant and anti-inflammatory mechanisms.

Electroencephalography and analgesics.

PubMed

Malver, Lasse Paludan; Brokjaer, Anne; Staahl, Camilla; Graversen, Carina; Andresen, Trine; Drewes, Asbjørn Mohr

2014-01-01

To assess centrally mediated analgesic mechanisms in clinical trials with pain patients, objective standardized methods such as electroencephalography (EEG) has many advantages. The aim of this review is to provide the reader with an overview of present findings in analgesics assessed with spontaneous EEG and evoked brain potentials (EPs) in humans. Furthermore, EEG methodologies will be discussed with respect to translation from animals to humans and future perspectives in predicting analgesic efficacy. We searched PubMed with MeSH terms 'analgesics', 'electroencephalography' and 'evoked potentials' for relevant articles. Combined with a search in their reference lists 15 articles on spontaneous EEG and 55 papers on EPs were identified. Overall, opioids produced increased activity in the delta band in the spontaneous EEG, but increases in higher frequency bands were also seen. The EP amplitudes decreased in the majority of studies. Anticonvulsants used as analgesics showed inconsistent results. The N-methyl-D-aspartate receptor antagonist ketamine showed an increase in the theta band in spontaneous EEG and decreases in EP amplitudes. Tricyclic antidepressants increased the activity in the delta, theta and beta bands in the spontaneous EEG while EPs were inconsistently affected. Weak analgesics were mainly investigated with EPs and a decrease in amplitudes was generally observed. This review reveals that both spontaneous EEG and EPs are widely used as biomarkers for analgesic drug effects. Methodological differences are common and a more uniform approach will further enhance the value of such biomarkers for drug development and prediction of treatment response in individual patients. © 2013 The British Pharmacological Society.

It's a two-way street: Automatic and controlled processes in children's emotional responses to moral transgressions.

PubMed

Dys, Sebastian P; Malti, Tina

2016-12-01

This study examined children's automatic, spontaneous emotional reactions to everyday moral transgressions and their relations with self-reported emotions, which are more complex and infused with controlled cognition. We presented children ​(N=242 4-, 8-, and 12-year-olds) with six everyday moral transgression scenarios in an experimental setting, and both their spontaneous facial emotional reactions and self-reported emotions in the role of the transgressor were recorded. We found that across age self-reported guilt was positively associated with spontaneous fear, and self-reported anger was positively related to spontaneous sadness. In addition, we found a developmental increase in spontaneous sadness and decrease in spontaneous happiness. These results support the importance of automatic and controlled processes in evoking children's emotional responses to everyday moral transgressions. We conclude by providing potential explanations for how automatic and controlled processes function in children's everyday moral experiences and how these processes may change with age. Copyright © 2016 Elsevier Inc. All rights reserved.

Patterns of fast synaptic cholinergic activation of neurons in the celiac ganglia of cats.

PubMed

Niel, J P; Clerc, N; Jule, Y

1988-12-01

Fast nicotinic transmission was studied in vitro in neurons of isolated cat celiac ganglia. In the absence of nerve stimulation, neurons could be classified into three types: silent neurons, synaptically activated neurons, and spontaneously discharging neurons. In all three types, fast synaptic activation could be obtained in single neurons by stimulating with a single pulse both the splanchnic nerves or one of the peripheral nerves connected to the ganglia. During repetitive nerve stimulation, a gradual depression of the central and peripheral fast nicotinic activation occurred, which was not affected by phentolamine plus propranolol, domperidone, atropine, or naloxone. Repetitive nerve stimulation was followed by a long lasting discharge of excitatory postsynaptic potentials and action potentials that decreased gradually with time. This discharge, which was probably due to presynaptic or prejunctional facilitation of acetylcholine release from cholinergic terminals, was reduced by the application of phentolamine plus propranolol, domperidone, or atropine and increased with naloxone. The existence of the mechanisms described in this study reflects the complexity of the integrative processes at work in neurons of the cat celiac ganglia that involve fast synaptic cholinergic activation.

Can the use of humor in psychotherapy be taught?

PubMed

Valentine, Lisa; Gabbard, Glen O

2014-02-01

Despite an abundance of literature detailing the potential benefits of the use of humor in therapy, humor is rarely taught to psychiatric residents as a method of therapeutic intervention. This communication attempts to explain how current understanding of attachment theory and neuroscience may assist psychiatric faculty and supervisors in their teaching of humorous therapeutic interventions. This article reviews and synthesizes the extant literature on the use of humor, as well as recent work in neuroscience, attachment theory, and mentalization. Humor can be conceptualized as an instance of implicit relational knowing and may thus contribute significantly to the therapeutic action of psychotherapy as a subcategory of "moments of meeting" between therapist and patient. However, training residents to use humor in psychotherapy requires more individualized attention in supervision and classroom seminars. Factors such as individual proclivities for humorous repartee, mentalizing capacity, and an authentic interest in adding humor to the session may be necessary to incorporate spontaneous humor into one's technique. New findings from the areas of attachment theory, neuroscience, and right-hemisphere learning are providing potential opportunities for sophisticated teaching of the use of humor in psychotherapy.

Roles of TRPV1 and TRPA1 in Spontaneous Pain from Inflamed Masseter Muscle.

PubMed

Wang, Sheng; Brigoli, Benjamin; Lim, Jongseuk; Karley, Alisha; Chung, Man-Kyo

2018-06-08

Craniofacial muscle pain, such as spontaneous pain and bite-evoked pain, are major symptoms in patients with temporomandibular disorders and infection. However, the underlying mechanisms of muscle pain, especially mechanisms of highly prevalent spontaneous pain, are poorly understood. Recently, we reported that transient receptor potential vanilloid 1 (TRPV1) contributes to spontaneous pain but only marginally contributes to bite-evoked pain during masseter inflammation. Here, we investigated the role of transient receptor potential ankyrin 1 (TRPA1) in spontaneous and bite-evoked pain during masseter inflammation, and dissected the relative contributions of TRPA1 and TRPV1. Masseter inflammation increased mouse grimace scale (MGS) scores and face wiping behaviors. Pharmacological or genetic inhibition of TRPA1 significantly attenuated MGS but not face wiping behaviors. MGS scores were also attenuated by scavenging putative endogenous ligands for TRPV1 or TRPA1. Simultaneous inhibition of TRPA1 by AP18 and TRPV1 by AMG9810 in masseter muscle resulted in robust inhibition of both MGS and face wiping behaviors. Administration of AP18 or AMG9810 to masseter muscle induced conditioned place preference (CPP). The extent of CPP following simultaneous administration of AP18 and AMG9810 was greater than that induced by the individual antagonists. In contrast, inflammation-induced reduction of bite force was not affected by the inhibition of TRPA1 alone or in combination with TRPV1. These results suggest that simultaneous inhibition of TRPV1 and TRPA1 produces additive relief of spontaneous pain, but does not ameliorate bite-evoked pain during masseter inflammation. Our results provide further evidence that distinct mechanisms underlie spontaneous and bite-evoked pain from inflamed masseter muscle. Copyright © 2018. Published by Elsevier Ltd.

Formation of Martian Gullies by the Action of Liquid Water Flowing Under Current Martian Environmental Conditions

NASA Technical Reports Server (NTRS)

Heldmann, J. L.; Toon, O. B.; Pollard, W. H.; Mellon, M. T.; Pitlick, J.; McKay, C. P.; Andersen, D. T.

2005-01-01

Images from the Mars Orbiter Camera (MOC) on the Mars Global Surveyor (MGS) spacecraft show geologically young small-scale features resembling terrestrial water-carved gullies. An improved understanding of these features has the potential to reveal important information about the hydrological system on Mars, which is of general interest to the planetary science community as well as the field of astrobiology and the search for life on Mars. The young geologic age of these gullies is often thought to be a paradox because liquid water is unstable at the Martian surface. Current temperatures and pressures are generally below the triple point of water (273 K, 6.1 mbar) so that liquid water will spontaneously boil and/or freeze. We therefore examine the flow of water on Mars to determine what conditions are consistent with the observed features of the gullies.

Biaxial ferromagnetic liquid crystal colloids

PubMed Central

Liu, Qingkun; Ackerman, Paul J.; Lubensky, Tom C.; Smalyukh, Ivan I.

2016-01-01

The design and practical realization of composite materials that combine fluidity and different forms of ordering at the mesoscopic scale are among the grand fundamental science challenges. These composites also hold a great potential for technological applications, ranging from information displays to metamaterials. Here we introduce a fluid with coexisting polar and biaxial ordering of organic molecular and magnetic colloidal building blocks exhibiting the lowest symmetry orientational order. Guided by interactions at different length scales, rod-like organic molecules of this fluid spontaneously orient along a direction dubbed “director,” whereas magnetic colloidal nanoplates order with their dipole moments parallel to each other but pointing at an angle to the director, yielding macroscopic magnetization at no external fields. Facile magnetic switching of such fluids is consistent with predictions of a model based on competing actions of elastic and magnetic torques, enabling previously inaccessible control of light. PMID:27601668

Visual thinking in action: visualizations as used on whiteboards.

PubMed

Walny, Jagoda; Carpendale, Sheelagh; Riche, Nathalie Henry; Venolia, Gina; Fawcett, Philip

2011-12-01

While it is still most common for information visualization researchers to develop new visualizations from a data- or taskdriven perspective, there is growing interest in understanding the types of visualizations people create by themselves for personal use. As part of this recent direction, we have studied a large collection of whiteboards in a research institution, where people make active use of combinations of words, diagrams and various types of visuals to help them further their thought processes. Our goal is to arrive at a better understanding of the nature of visuals that are created spontaneously during brainstorming, thinking, communicating, and general problem solving on whiteboards. We use the qualitative approaches of open coding, interviewing, and affinity diagramming to explore the use of recognizable and novel visuals, and the interplay between visualization and diagrammatic elements with words, numbers and labels. We discuss the potential implications of our findings on information visualization design. © 2011 IEEE

Basal Ganglia Beta Oscillations Accompany Cue Utilization

PubMed Central

Leventhal, Daniel K.; Gage, Gregory J.; Schmidt, Robert; Pettibone, Jeffrey R.; Case, Alaina C.; Berke, Joshua D.

2012-01-01

SUMMARY Beta oscillations in cortical-basal ganglia (BG) circuits have been implicated in normal movement suppression and motor impairment in Parkinson’s disease. To dissect the functional correlates of these rhythms we compared neural activity during four distinct variants of a cued choice task in rats. Brief beta (~20 Hz) oscillations occurred simultaneously throughout the cortical-BG network, both spontaneously and at precise moments of task performance. Beta phase was rapidly reset in response to salient cues, yet increases in beta power were not rigidly linked to cues, movements, or movement suppression. Rather, beta power was enhanced after cues were used to determine motor output. We suggest that beta oscillations reflect a postdecision stabilized state of cortical-BG networks, which normally reduces interference from alternative potential actions. The abnormally strong beta seen in Parkinson’s Disease may reflect overstabilization of these networks, producing pathological persistence of the current motor state. PMID:22325204

Metabotropic glutamate receptors 1 and 5 differentially regulate bulbar dopaminergic cell function.

PubMed

Jian, Kuihuan; Cifelli, Pierangelo; Pignatelli, Angela; Frigato, Elena; Belluzzi, Ottorino

2010-10-01

Effects of activation of metabotropic glutamatergic receptors (mGluR) were investigated in mouse dopaminergic olfactory bulb neurons. After blockage of ionotropic receptors, focal application of glutamate or of group I/II mGluR agonist t-ACPD resulted in a depolarization, paralleled by an inward current in voltage-clamp conditions. The Group I agonist DHPG induced a depolarization, which could be largely blocked by mGluR1 antagonists. The DHPG action i) was prevented by buffering intracellular Ca(2+) with BAPTA and by a phospholipase C inhibitor; ii) was not affected by the block of Ca(2+) entry, and iii) was blocked by inhibitors of the Na(+)/Ca(2+) exchanger. These observations were interpreted as a mGluR1-mediated intracellular Ca(2+) release, followed by the activation of an electrogenic Na(+)/Ca(2+) exchanger. The mGluR5 agonist CHPG induced a hyperpolarization of membrane potential, resulting in a decrease of the spontaneous firing frequency. CHPG induced i) a decrease in membrane resistance; ii) an increase in the action potential repolarization rate, and iii) an increase in the amplitude of the afterhyperpolarization. This was interpreted as a mGluR5-mediated opening of a K(+) conductance. These data suggest that mGluR1 and mGluR5 play different and non-overlapping roles in the regulation of the excitability of bulbar dopaminergic neurons. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Neuroprotective action and free radical scavenging activity of Guttiferone-A, a naturally occurring prenylated benzophenone.

PubMed

Nuñez-Figueredo, Y; García-Pupo, L; Ramírez-Sánchez, J; Alcántara-Isaac, Y; Cuesta-Rubio, O; Hernández, R D; Naal, Z; Curti, C; Pardo-Andreu, G L

2012-12-01

Reactive oxygen species (ROS) are important mediators in a number of neurodegenerative diseases and molecules capable of scavenging ROS may be a feasible strategy for protecting neuronal cells. We previously demonstrated a powerful iron-chelating action of Guttiferone-A (GA), a naturally occurring polyphenol, on oxidative stress injuries initiated by iron overload. Here we addressed the neuroprotective potential of GA in hydrogen peroxide and glutamate-induced injury on rat's primary culture of cortical neurons and PC12 cells, respectively, and antioxidant properties concerning scavenging and anti-lipoperoxidative activities in cell-free models. The decrease in cell viability induced by each of the toxins, assessed by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay, was significantly attenuated by GA. In addition, GA was found to be a potent antioxidant, as shown by (i) inhibition of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical reduction (EC50=20.0 μM), (ii) prevention against chemically or electrochemically generated superoxide radicals, (iii) inhibition of spontaneous brain lipid peroxidation and (iv) interference with the Fenton reaction. These results indicate that GA exerts neuroprotective effects against H2O2 or glutamate toxicity and its antioxidant activity, demonstrated in vitro, could be at least partly involved. They also suggest a promising potential for GA as a therapeutic agent against neurodegenerative diseases involving ROS and oxidative damage. © Georg Thieme Verlag KG Stuttgart · New York.

Co-Thought and Co-Speech Gestures Are Generated by the Same Action Generation Process

ERIC Educational Resources Information Center

Chu, Mingyuan; Kita, Sotaro

2016-01-01

People spontaneously gesture when they speak (co-speech gestures) and when they solve problems silently (co-thought gestures). In this study, we first explored the relationship between these 2 types of gestures and found that individuals who produced co-thought gestures more frequently also produced co-speech gestures more frequently (Experiments…

Teacher Flow and Its Relationship to School Mindfulness and Enabling School Structure

ERIC Educational Resources Information Center

Marshall, Robert Paul, III.

2013-01-01

Teacher flow experience is a phenomenon occurring when a teacher becomes totally absorbed into a given task at hand. The clearest indication of teacher flow is action-awareness merging; or, the degree in which an activity becomes so spontaneous and automatic that teachers lose conscious awareness of themselves as they perform their duties. This…

Basic emotions and adaptation. A computational and evolutionary model.

PubMed

Pacella, Daniela; Ponticorvo, Michela; Gigliotta, Onofrio; Miglino, Orazio

2017-01-01

The core principles of the evolutionary theories of emotions declare that affective states represent crucial drives for action selection in the environment and regulated the behavior and adaptation of natural agents in ancestrally recurrent situations. While many different studies used autonomous artificial agents to simulate emotional responses and the way these patterns can affect decision-making, few are the approaches that tried to analyze the evolutionary emergence of affective behaviors directly from the specific adaptive problems posed by the ancestral environment. A model of the evolution of affective behaviors is presented using simulated artificial agents equipped with neural networks and physically inspired on the architecture of the iCub humanoid robot. We use genetic algorithms to train populations of virtual robots across generations, and investigate the spontaneous emergence of basic emotional behaviors in different experimental conditions. In particular, we focus on studying the emotion of fear, therefore the environment explored by the artificial agents can contain stimuli that are safe or dangerous to pick. The simulated task is based on classical conditioning and the agents are asked to learn a strategy to recognize whether the environment is safe or represents a threat to their lives and select the correct action to perform in absence of any visual cues. The simulated agents have special input units in their neural structure whose activation keep track of their actual "sensations" based on the outcome of past behavior. We train five different neural network architectures and then test the best ranked individuals comparing their performances and analyzing the unit activations in each individual's life cycle. We show that the agents, regardless of the presence of recurrent connections, spontaneously evolved the ability to cope with potentially dangerous environment by collecting information about the environment and then switching their behavior to a genetically selected pattern in order to maximize the possible reward. We also prove the determinant presence of an internal time perception unit for the robots to achieve the highest performance and survivability across all conditions.

Role of phosphatidylinositol 3-kinase in angiotensin II regulation of norepinephrine neuromodulation in brain neurons of the spontaneously hypertensive rat.

PubMed

Yang, H; Raizada, M K

1999-04-01

Chronic stimulation of norepinephrine (NE) neuromodulation by angiotensin II (Ang II) involves activation of the Ras-Raf-MAP kinase signal transduction pathway in Wistar Kyoto (WKY) rat brain neurons. This pathway is only partially responsible for this heightened action of Ang II in the spontaneously hypertensive rat (SHR) brain neurons. In this study, we demonstrate that the MAP kinase-independent signaling pathway in the SHR neuron involves activation of PI3-kinase and protein kinase B (PKB/Akt). Ang II stimulated PI3-kinase activity in both WKY and SHR brain neurons and was accompanied by its translocation from the cytoplasmic to the nuclear compartment. Although the magnitude of stimulation by Ang II was comparable, the stimulation was more persistent in the SHR neuron compared with the WKY rat neuron. Inhibition of PI3-kinase had no significant effect in the WKY rat neuron. However, it caused a 40-50% attenuation of the Ang II-induced increase in norepinephrine transporter (NET) and tyrosine hydroxylase (TH) mRNAs and [3H]-NE uptake in the SHR neuron. In contrast, inhibition of MAP kinase completely attenuated Ang II stimulation of NET and TH mRNA levels in the WKY rat neuron, whereas it caused only a 45% decrease in the SHR neuron. However, an additive attenuation was observed when both kinases of the SHR neurons were inhibited. Ang II also stimulated PKB/Akt activity in both WKY and SHR neurons. This stimulation was 30% higher and lasted longer in the SHR neuron compared with the WKY rat neuron. In conclusion, these observations demonstrate an exclusive involvement of PI3-kinase-PKB-dependent signaling pathway in a heightened NE neuromodulatory action of Ang II in the SHR neuron. Thus, this study offers an excellent potential for the development of new therapies for the treatment of centrally mediated hypertension.

Disorientation, confabulation, and extinction capacity: clues on how the brain creates reality.

PubMed

Nahum, Louis; Ptak, Radek; Leemann, Béatrice; Schnider, Armin

2009-06-01

Disorientation and confabulation often have a common course, independent of amnesia. Behaviorally spontaneous confabulation is the form in which patients act according to a false concept of reality; they fail to abandon action plans (anticipations) that do not pertain to the present situation. This continued enactment of previously valid but meanwhile invalidated anticipations can be conceived as deficient extinction capacity, that is, failure to integrate negative prediction errors into behavior. In this study, we explored whether disorientation and behaviorally spontaneous confabulation are associated with extinction failure. Twenty-five patients hospitalized for neurorehabilitation after first-ever brain injury who either had severe amnesia (n = 17), an orbitofrontal lesion (n = 14), or both (n = 6) were tested regarding disorientation (questionnaire) and performed an experimental task of association learning and extinction. Five patients were also classified as behaviorally spontaneous confabulators. Extinction capacity explained 66% of the variance of orientation in the whole group of patients (amnesics only, 56%; orbitofrontal group only, 90%), whereas association learning explained only 17% of the variance in the whole group (amnesics only, 7%; orbitofrontal group only, 16%). Also, extinction capacity, but not association learning, significantly distinguished between behaviorally spontaneous confabulators and all other subjects. Disorientation and behaviorally spontaneous confabulation are strongly and specifically associated with a failure of extinction, the ability to learn that previously appropriate anticipations no longer apply. Rather than invoking high-level monitoring processes, the human brain seems to make use of an ancient biological faculty-extinction-to keep thought and behavior in phase with reality.

Dynamo action in stratified convection with overshoot

NASA Technical Reports Server (NTRS)

Nordlund, Ake; Brandenburg, Axel; Jennings, Richard L.; Rieutord, Michel; Ruokolainen, Juha; Stein, Robert F.; Tuominen, Ilkka

1992-01-01

Results are presented from direct simulations of turbulent compressible hydromagnetic convection above a stable overshoot layer. Spontaneous dynamo action occurs followed by saturation, with most of the generated magnetic field appearing as coherent flux tubes in the vicinity of strong downdrafts, where both the generation and destruction of magnetic field is most vigorous. Whether or not this field is amplified depends on the sizes of the magnetic Reynolds and magnetic Prandtl numbers. Joule dissipation is balanced mainly by the work done against the magnetic curvature force. It is this curvature force which is also responsible for the saturation of the dynamo.

Muscarinic acetylcholine receptors control baseline activity and Hebbian stimulus timing-dependent plasticity in fusiform cells of the dorsal cochlear nucleus.

PubMed

Stefanescu, Roxana A; Shore, Susan E

2017-03-01

Cholinergic modulation contributes to adaptive sensory processing by controlling spontaneous and stimulus-evoked neural activity and long-term synaptic plasticity. In the dorsal cochlear nucleus (DCN), in vitro activation of muscarinic acetylcholine receptors (mAChRs) alters the spontaneous activity of DCN neurons and interacts with N -methyl-d-aspartate (NMDA) and endocannabinoid receptors to modulate the plasticity of parallel fiber synapses onto fusiform cells by converting Hebbian long-term potentiation to anti-Hebbian long-term depression. Because noise exposure and tinnitus are known to increase spontaneous activity in fusiform cells as well as alter stimulus timing-dependent plasticity (StTDP), it is important to understand the contribution of mAChRs to in vivo spontaneous activity and plasticity in fusiform cells. In the present study, we blocked mAChRs actions by infusing atropine, a mAChR antagonist, into the DCN fusiform cell layer in normal hearing guinea pigs. Atropine delivery leads to decreased spontaneous firing rates and increased synchronization of fusiform cell spiking activity. Consistent with StTDP alterations observed in tinnitus animals, atropine infusion induced a dominant pattern of inversion of StTDP mean population learning rule from a Hebbian to an anti-Hebbian profile. Units preserving their initial Hebbian learning rules shifted toward more excitatory changes in StTDP, whereas units with initial suppressive learning rules transitioned toward a Hebbian profile. Together, these results implicate muscarinic cholinergic modulation as a factor in controlling in vivo fusiform cell baseline activity and plasticity, suggesting a central role in the maladaptive plasticity associated with tinnitus pathology. NEW & NOTEWORTHY This study is the first to use a novel method of atropine infusion directly into the fusiform cell layer of the dorsal cochlear nucleus coupled with simultaneous recordings of neural activity to clarify the contribution of muscarinic acetylcholine receptors (mAChRs) to in vivo fusiform cell baseline activity and auditory-somatosensory plasticity. We have determined that blocking the mAChRs increases the synchronization of spiking activity across the fusiform cell population and induces a dominant pattern of inversion in their stimulus timing-dependent plasticity. These modifications are consistent with similar changes established in previous tinnitus studies, suggesting that mAChRs might have a critical contribution in mediating the maladaptive alterations associated with tinnitus pathology. Blocking mAChRs also resulted in decreased fusiform cell spontaneous firing rates, which is in contrast with their tinnitus hyperactivity, suggesting that changes in the interactions between the cholinergic and GABAergic systems might also be an underlying factor in tinnitus pathology. Copyright © 2017 the American Physiological Society.

Spontaneous Massive Hemothorax in a Patient with Neurofibromatosis Type 1 with Successful Transarterial Embolization

PubMed Central

Rookkapan, Sorracha; Tanutit, Pramot; Pakdeejit, Songklod; Songjamrat, Apiradee; Sungsiri, Jitpreedee

2013-01-01

Vascular involvement in neurofibromatosis type 1 is rare but has the potential to be fatal. We report a case of a patient with spontaneous rupture of a left intercostal artery aneurysm, which presented as a massive left hemothorax and was successfully treated by transarterial coil embolization. PMID:23323035

Thoughts and sensations, twin galaxies of the inner space: The propensity to mind-wander relates to spontaneous sensations arising on the hands.

PubMed

Michael, George A; Tapiero, Isabelle; Gálvez-García, Germán; Jacquot, Laurence

2017-10-01

Sensations and thoughts have been described as potentially related to self-awareness. We therefore asked whether sensations that arise in the absence of external triggers, i.e., spontaneous sensations (SPS), which were shown to relate to interoception and perception of the self, vary as a function of the individual propensity to generate spontaneous thoughts, i.e., mind-wandering. The Mind Wandering Questionnaire (MWQ) was used as a specific tool to assess the frequency and propensity to mind-wander several weeks before completing an SPS task. Correlational analyses between the MWQ score and SPS showed that greater propensity to mind-wander coincided with widespread perception of SPS, while lesser propensity to mind-wander coincided with more spatially restricted perception of SPS. The results are interpreted in light of the role of spontaneous thoughts and sensations in self-awareness. The potential psychological processes and the way they might regulate the relation between mind-wandering and the perception of SPS are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

Contractile activity of the bladder urothelium/lamina propria and its regulation by nitric oxide.

PubMed

Moro, Christian; Leeds, Charlotte; Chess-Williams, Russ

2012-01-15

In the bladder, nitric oxide (NO) is released from neuronal and non-neuronal sources, but its actions are unclear. Strips of urothelium plus lamina propria contract in response to agonists and develop spontaneous phasic contractions, and the aim of this study was to investigate the influence of NO on this activity. Isolated strips of urothelium/lamina propria from porcine bladder developed spontaneous contractions (3.5 ± 0.3 cycles/min) and contracted in response to carbachol and electrical field stimulation (EFS). The NO synthase inhibitor N(ω)-nitro-l-arginine (L-NNA, 100 μM) had no effects on the tissues, but the NO donors diethylamine NONOate (DEANO, 100 μM) and nitroprusside (10 μM) caused relaxation, slowed the spontaneous rate of contractions and inhibited responses to carbachol. Maximum tonic contractions to carbachol were reduced by 17 ± 4% (P<0.001) and 35 ± 5% (P<0.001) by DEANO and nitroprusside respectively and the potency of carbachol was also reduced. Carbachol also increased the spontaneous frequency of contraction and these rate responses were again inhibited by DEANO and nitroprusside, but unaffected by L-NNA. Similarly, responses to EFS were significantly depressed (52-70%) by DEANO (P<0.05), but were unaffected by L-NNA. These data demonstrate spontaneous contractile activity and also nerve and agonist-induced tonic contractile activity within the urothelium and lamina propria. This activity is sensitive to depression by NO, but NO does not appear to be spontaneously released to influence this activity, nor does it appear to be released by muscarinic receptor stimulation. However the results suggest that in situations where NO production is increased, NO can influence the contractile activity of this tissue. Copyright © 2011 Elsevier B.V. All rights reserved.

Costs and consequences of abortions to women and their households: a cross-sectional study in Ouagadougou, Burkina Faso.

PubMed

Ilboudo, Patrick G C; Greco, Giulia; Sundby, Johanne; Torsvik, Gaute

2015-05-01

Little is known about the costs and consequences of abortions to women and their households. Our aim was to study both costs and consequences of induced and spontaneous abortions and complications. We carried out a cross-sectional study between February and September 2012 in Ouagadougou, the capital city of Burkina Faso. Quantitative data of 305 women whose pregnancy ended with either an induced or a spontaneous abortion were prospectively collected on sociodemographic, asset ownership, medical and health expenditures including pre-referral costs following the patient's perspective. Descriptive analysis and regression analysis of costs were performed. We found that women with induced abortion were often single or never married, younger, more educated and had earlier pregnancies than women with spontaneous abortion. They also tended to be more often under parents' guardianship compared with women with spontaneous abortion. Women with induced abortion paid much more money to obtain abortion and treatment of the resulting complications compared with women with spontaneous abortion: US$89 (44 252 CFA ie franc of the African Financial Community) vs US$56 (27 668 CFA). The results also suggested that payments associated with induced abortion were catastrophic as they consumed 15% of the gross domestic product per capita. Additionally, 11-16% of total households appeared to have resorted to coping strategies in order to face costs. Both induced and spontaneous abortions may incur high expenses with short-term economic repercussions on households' poverty. Actions are needed in order to reduce the financial burden of abortion costs and promote an effective use of contraceptives. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2014.

Urothelial/lamina propria spontaneous activity and the role of M3 muscarinic receptors in mediating rate responses to stretch and carbachol.

PubMed

Moro, Christian; Uchiyama, Jumpei; Chess-Williams, Russ

2011-12-01

To investigate the effects of tissue stretch and muscarinic receptor stimulation on the spontaneous activity of the urothelium/lamina propria and identify the specific receptor subtype mediating these responses. Isolated strips of porcine urothelium with lamina propria were set up for in vitro recording of contractile activity. Muscarinic receptor subtype-selective antagonists were used to identify the receptors influencing the contractile rate responses to stretch and stimulation with carbachol. Isolated strips of urothelium with lamina propria developed spontaneous contractions (3.7 cycles/min) that were unaffected by tetrodotoxin, Nω-nitro-L-arginine, or indomethacin. Carbachol (1 μM) increased the spontaneous contractile rate of these tissue strips by 122% ± 27% (P < .001). These responses were significantly depressed in the presence of the M3-selective muscarinic antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (10-30 nM) but were not affected by the M1-selective antagonist pirenzepine (30-100 nM) or the M2-selective antagonist methoctramine (0.1-1 μM). Stretching of the tissue also caused an increase in the spontaneous contractile rate, and these responses were abolished by atropine (1 μM) and low concentrations of 4-diphenylacetoxy-N-methylpiperidine methiodide (10 nM). Darifenacin, oxybutynin, tolterodine, and solifenacin (1 μM) all significantly depressed the frequency responses to carbachol (1 μM). The urothelium with the lamina propria exhibits a spontaneous contractile activity that is increased during stretch. The mechanism appears to involve endogenous acetylcholine release acting on M3 muscarinic receptors. Anticholinergic drugs used clinically depress the responses of these tissues, and this mechanism might represent an additional site of action for these drugs in the treatment of bladder overactivity. Copyright © 2011 Elsevier Inc. All rights reserved.

Spontaneous supersymmetry breaking in two dimensional lattice super QCD

DOE PAGES

Catterall, Simon; Veernala, Aarti

2015-10-02

We report on a non-perturbative study of two dimensional N=(2,2) super QCD. Our lattice formulation retains a single exact supersymmetry at non-zero lattice spacing, and contains N f fermions in the fundamental representation of a U(N c) gauge group. The lattice action we employ contains an additional Fayet-Iliopoulos term which is also invariant under the exact lattice supersymmetry. This work constitutes the first numerical study of this theory which serves as a toy model for understanding some of the issues that are expected to arise in four dimensional super QCD. As a result, we present evidence that the exact supersymmetrymore » breaks spontaneously when N f < N c in agreement with theoretical expectations.« less

An Investigation into the Cognition Behind Spontaneous String Pulling in New Caledonian Crows

PubMed Central

Taylor, Alex H.; Medina, Felipe S.; Holzhaider, Jennifer C.; Hearne, Lindsay J.; Hunt, Gavin R.; Gray, Russell D.

2010-01-01

The ability of some bird species to pull up meat hung on a string is a famous example of spontaneous animal problem solving. The “insight” hypothesis claims that this complex behaviour is based on cognitive abilities such as mental scenario building and imagination. An operant conditioning account, in contrast, would claim that this spontaneity is due to each action in string pulling being reinforced by the meat moving closer and remaining closer to the bird on the perch. We presented experienced and naïve New Caledonian crows with a novel, visually restricted string-pulling problem that reduced the quality of visual feedback during string pulling. Experienced crows solved this problem with reduced efficiency and increased errors compared to their performance in standard string pulling. Naïve crows either failed or solved the problem by trial and error learning. However, when visual feedback was available via a mirror mounted next to the apparatus, two naïve crows were able to perform at the same level as the experienced group. Our results raise the possibility that spontaneous string pulling in New Caledonian crows may not be based on insight but on operant conditioning mediated by a perceptual-motor feedback cycle. PMID:20179759

Spontaneous rupture of the spleen detected on CT as the initial manifestation of infectious mononucleosis.

PubMed

Gayer, Gabriela; Zandman-Goddard, Gisele; Kosych, Elena; Apter, Sara

2003-04-01

Spontaneous splenic rupture after infectious mononucleosis (IM) is a rare, potentially fatal complication of IM, occurring in 0.1-0.5% of patients with proven IM. It usually occurs several weeks after the onset of symptoms, but may, rarely, be the initial manifestation of the disease. The patient is usually examined as an emergency due to severe abdominal pain and a falling hematocrit. The radiologist should be aware of the pathologic conditions involving the spleen which may lead to its spontaneous rupture.

Spontaneous Polariton Currents in Periodic Lateral Chains.

PubMed

Nalitov, A V; Liew, T C H; Kavokin, A V; Altshuler, B L; Rubo, Y G

2017-08-11

We predict spontaneous generation of superfluid polariton currents in planar microcavities with lateral periodic modulation of both the potential and decay rate. A spontaneous breaking of spatial inversion symmetry of a polariton condensate emerges at a critical pumping, and the current direction is stochastically chosen. We analyze the stability of the current with respect to the fluctuations of the condensate. A peculiar spatial current domain structure emerges, where the current direction is switched at the domain walls, and the characteristic domain size and lifetime scale with the pumping power.

Driving factors of the communities of phytophagous and predatory mites in a physic nut plantation and spontaneous plants associated.

PubMed

Cruz, Wilton P; Sarmento, Renato A; Teodoro, Adenir V; Neto, Marçal P; Ignacio, Maíra

2013-08-01

Seasonal changes in climate and plant diversity are known to affect the population dynamics of both pests and natural enemies within agroecosystems. In Brazil, spontaneous plants are usually tolerated in small-scale physic nut plantations over the year, which in turn may mediate interactions between pests and natural enemies within this agroecosystem. Here, we aimed to access the influence of seasonal variation of abiotic (temperature, relative humidity and rainfall) and biotic (diversity of spontaneous plants, overall richness and density of mites) factors on the communities of phytophagous and predatory mites found in a physic nut plantation and its associated spontaneous plants. Mite sampling was monthly conducted in dicotyledonous and monocotyledonous leaves of spontaneous plants as well as in physic nut shrubs over an entire year. In the dry season there was a higher abundance of phytophagous mites (Tenuipalpidae, Tarsonemidae and Tetranychidae) on spontaneous plants than on physic nut shrubs, while predatory mites (Phytoseiidae) showed the opposite pattern. The overall density of mites on spontaneous plants increased with relative humidity and diversity of spontaneous plants. Rainfall was the variable that most influenced the density of mites inhabiting physic nut shrubs. Agroecosystems comprising spontaneous plants associated with crops harbour a rich mite community including species of different trophic levels which potentially benefit natural pest control due to increased diversity and abundance of natural enemies.

Spontaneous evaluative inferences and their relationship to spontaneous trait inferences.

PubMed

Schneid, Erica D; Carlston, Donal E; Skowronski, John J

2015-05-01

Three experiments are reported that explore affectively based spontaneous evaluative impressions (SEIs) of stimulus persons. Experiments 1 and 2 used modified versions of the savings in relearning paradigm (Carlston & Skowronski, 1994) to confirm the occurrence of SEIs, indicating that they are equivalent whether participants are instructed to form trait impressions, evaluative impressions, or neither. These experiments also show that SEIs occur independently of explicit recall for the trait implications of the stimuli. Experiment 3 provides a single dissociation test to distinguish SEIs from spontaneous trait inferences (STIs), showing that disrupting cognitive processing interferes with a trait-based prediction task that presumably reflects STIs, but not with an affectively based social approach task that presumably reflects SEIs. Implications of these findings for the potential independence of spontaneous trait and evaluative inferences, as well as limitations and important steps for future study are discussed. (c) 2015 APA, all rights reserved).

Spontaneous resolution of postoperative lumbar pseudomeningoceles: A report of four cases.

PubMed

Solomon, Prince; Sekharappa, Vijay; Krishnan, Venkatesh; David, Kenny Samuel

2013-07-01

Pseudomeningocele is an extradural cerebrospinal fluid collection arising from a dural defect, that may be congenital, traumatic, or more commonly as a result of postoperative complication. Majority of the postoperative pseudomeningoceles occurring after lumbar spine surgeries are small and resolve spontaneously. However, large pseudomeningoceles are rare and spontaneous resolution of such pseudomeningoceles has not been described. We report four cases of postoperative large lumbar pseudomeningoceles that presented as asymptomatic soft fluctuant swelling over the back which resolved spontaneously. We also reviewed the related literatures and operative records of these patients to find the possible mechanism of occurrence, their management, prevention, and reasons for spontaneous resolution. We conclude that nonoperative management under close observation can be employed for asymptomatic postoperative large lumbar pseudomeningoceles. Surgical exploration and repair should be reserved for symptomatic cases presenting with clinical features of intracranial hypotension, worsening neurology, external fistula or infection, thereby avoiding morbidity and potential complications associated with surgical treatment.

Spontaneous decoherence of coupled harmonic oscillators confined in a ring

NASA Astrophysics Data System (ADS)

Gong, ZhiRui; Zhang, ZhenWei; Xu, DaZhi; Zhao, Nan; Sun, ChangPu

2018-04-01

We study the spontaneous decoherence of coupled harmonic oscillators confined in a ring container, where the nearest-neighbor harmonic potentials are taken into consideration. Without any external symmetry-breaking field or surrounding environment, the quantum superposition state prepared in the relative degrees of freedom gradually loses its quantum coherence spontaneously. This spontaneous decoherence is interpreted by the gauge couplings between the center-of-mass and the relative degrees of freedoms, which actually originate from the symmetries of the ring geometry and the corresponding nontrivial boundary conditions. In particular, such spontaneous decoherence does not occur at all at the thermodynamic limit because the nontrivial boundary conditions become the trivial Born-von Karman boundary conditions when the perimeter of the ring container tends to infinity. Our investigation shows that a thermal macroscopic object with certain symmetries has a chance for its quantum properties to degrade even without applying an external symmetry-breaking field or surrounding environment.

Spontaneous olfactory receptor neuron activity determines follower cell response properties

PubMed Central

Joseph, Joby; Dunn, Felice A.; Stopfer, Mark

2012-01-01

Noisy or spontaneous activity is common in neural systems and poses a challenge to detecting and discriminating signals. Here we use the locust to answer fundamental questions about noise in the olfactory system: Where does spontaneous activity originate? How is this activity propagated or reduced throughout multiple stages of neural processing? What mechanisms favor the detection of signals despite the presence of spontaneous activity? We found that spontaneous activity long observed in the secondary projection neurons (PNs) originates almost entirely from the primary olfactory receptor neurons (ORNs) rather than from spontaneous circuit interactions in the antennal lobe, and that spontaneous activity in ORNs tonically depolarizes the resting membrane potentials of their target PNs and local neurons (LNs), and indirectly tonically depolarizes tertiary Kenyon cells (KCs). However, because these neurons have different response thresholds, in the absence of odor stimulation, ORNs and PNs display a high spontaneous firing rate but KCs are nearly silent. Finally, we used a simulation of the olfactory network to show that discrimination of signal and noise in the KCs is best when threshold levels are set so that baseline activity in PNs persists. Our results show how the olfactory system benefits from making a signal detection decision after a point of maximal information convergence, e.g., after KCs pool inputs from many PNs. PMID:22357872

Spontaneous breathing during lung-protective ventilation in an experimental acute lung injury model: high transpulmonary pressure associated with strong spontaneous breathing effort may worsen lung injury.

PubMed

Yoshida, Takeshi; Uchiyama, Akinori; Matsuura, Nariaki; Mashimo, Takashi; Fujino, Yuji

2012-05-01

We investigated whether potentially injurious transpulmonary pressure could be generated by strong spontaneous breathing and exacerbate lung injury even when plateau pressure is limited to <30 cm H2O. Prospective, randomized, animal study. University animal research laboratory. Thirty-two New Zealand White rabbits. Lavage-injured rabbits were randomly allocated to four groups to receive low or moderate tidal volume ventilation, each combined with weak or strong spontaneous breathing effort. Inspiratory pressure for low tidal volume ventilation was set at 10 cm H2O and tidal volume at 6 mL/kg. For moderate tidal volume ventilation, the values were 20 cm H2O and 7-9 mL/kg. The groups were: low tidal volume ventilation+spontaneous breathingweak, low tidal volume ventilation+spontaneous breathingstrong, moderate tidal volume ventilation+spontaneous breathingweak, and moderate tidal volume ventilation+spontaneous breathingstrong. Each group had the same settings for positive end-expiratory pressure of 8 cm H2O. Respiratory variables were measured every 60 mins. Distribution of lung aeration and alveolar collapse were histologically evaluated. Low tidal volume ventilation+spontaneous breathingstrong showed the most favorable oxygenation and compliance of respiratory system, and the best lung aeration. By contrast, in moderate tidal volume ventilation+spontaneous breathingstrong, the greatest atelectasis with numerous neutrophils was observed. While we applied settings to maintain plateau pressure at <30 cm H2O in all groups, in moderate tidal volume ventilation+spontaneous breathingstrong, transpulmonary pressure rose >33 cm H2O. Both minute ventilation and respiratory rate were higher in the strong spontaneous breathing groups. Even when plateau pressure is limited to <30 cm H2O, combined with increased respiratory rate and tidal volume, high transpulmonary pressure generated by strong spontaneous breathing effort can worsen lung injury. When spontaneous breathing is preserved during mechanical ventilation, transpulmonary pressure and tidal volume should be strictly controlled to prevent further lung injury.

[Conservative management of spontaneous splenic rupture as a complication of infectious mononucleosis: two case reports and literature review].

PubMed

Steiner-Linder, A; Ballmer, P E; Haller, A

2000-11-04

We report on conservative management of 2 patients with spontaneous splenic rupture associated with infectious mononucleosis. Both patients had an unremarkable hospital course and were discharged within 7 days of admission. Resolution of the haematoma was followed by ultrasound monitoring during the hospital stay. A literature review to 1999 shows that approximately 45 patients with serologically proven infectious mononucleosis have suffered spontaneous rupture of the spleen. Spontaneous splenic rupture is a rare but potentially fatal complication of infectious mononucleosis. Although splenectomy has been advocated in the past as the definitive therapy, we recommend that non-surgical management be considered in haemodynamically stable patients, to avoid the complications of splenectomy (e.g. post-splenectomy sepsis).

No Evidence for Spontaneous Lipid Transfer at ER-PM Membrane Contact Sites.

PubMed

Merklinger, Elisa; Schloetel, Jan-Gero; Spitta, Luis; Thiele, Christoph; Lang, Thorsten

2016-04-01

Non-vesicular lipid transport steps play a crucial role in lipid trafficking and potentially include spontaneous exchange. Since membrane contact facilitates this lipid transfer, it is most likely to occur at membrane contact sites (MCS). However, to date it is unknown whether closely attached biological membranes exchange lipids spontaneously. We have set up a system for studying the exchange of lipids at MCS formed between the endoplasmic reticulum (ER) and the plasma membrane. Contact sites were stably anchored and the lipids cholesterol and phosphatidylcholine (PC) were not capable of transferring spontaneously into the opposed bilayer. We conclude that physical contact between two associated biological membranes is not sufficient for transfer of the lipids PC and cholesterol.

Coherent manipulation of spontaneous emission spectra in coupled semiconductor quantum well structures.

PubMed

Chen, Aixi

2014-11-03

In triple coupled semiconductor quantum well structures (SQWs) interacting with a coherent driving filed, a coherent coupling field and a weak probe field, spontaneous emission spectra are investigated. Our studies show emission spectra can easily be manipulated through changing the intensity of the driving and coupling field, detuning of the driving field. Some interesting physical phenomena such as spectral-line enhancement/suppression, spectral-line narrowing and spontaneous emission quenching may be obtained in our system. The theoretical studies of spontaneous emission spectra in SQWS have potential application in high-precision spectroscopy. Our studies are based on the real physical system [Appl. Phys. Lett.86(20), 201112 (2005)], and this scheme might be realizable with presently available techniques.

The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro Cocultures

PubMed Central

Trieschmann, Jan; Bettin, Daniel; Haustein, Moritz; Köster, Annette; Molcanyi, Marek; Halbach, Marcel; Hanna, Mira; Fouad, Mariam; Brockmeier, Konrad; Hescheler, Jürgen; Pfannkuche, Kurt; Hannes, Tobias

2016-01-01

Transplantation of stem cell-derived cardiomyocytes is one of the most promising therapeutic approaches after myocardial infarction, as loss of cardiomyocytes is virtually irreversible by endogenous repair mechanisms. In myocardial scars, transplanted cardiomyocytes will be in immediate contact with cardiac fibroblasts. While it is well documented how the electrophysiology of neonatal cardiomyocytes is modulated by cardiac fibroblasts of the same developmental stage, it is unknown how adult cardiac fibroblasts (aCFs) affect the function of embryonic stem cell-derived cardiomyocytes (ESC-CMs). To investigate the effects of aCFs on ESC-CM electrophysiology, we performed extra- and intracellular recordings of murine aCF-ESC-CM cocultures. We observed that spontaneous beating behaviour was highly irregular in aCF-ESC-CM cocultures compared to cocultures with mesenchymal stem cells (coefficient of variation of the interspike interval: 40.5 ± 15.2% versus 9.3 ± 2.0%, p = 0.008) and that action potential amplitude and maximal upstroke velocity (V max) were reduced (amplitude: 52.3 ± 1.7 mV versus 65.1 ± 1.5 mV, V max: 7.0 ± 1.0 V/s versus 36.5 ± 5.3 V/s), while action potential duration (APD) was prolonged (APD50: 25.6 ± 1.0 ms versus 16.8 ± 1.9 ms, p < 0.001; APD90: 52.2 ± 1.5 ms versus 43.3 ± 3.3 ms, p < 0.01) compared to controls. Similar changes could be induced by aCF-conditioned medium. We conclude that the presence of aCFs changes automaticity and induces potentially proarrhythmic changes of ESC-CM electrophysiology. PMID:26880949

The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro Cocultures.

PubMed

Trieschmann, Jan; Bettin, Daniel; Haustein, Moritz; Köster, Annette; Molcanyi, Marek; Halbach, Marcel; Hanna, Mira; Fouad, Mariam; Brockmeier, Konrad; Hescheler, Jürgen; Pfannkuche, Kurt; Hannes, Tobias

2016-01-01

Transplantation of stem cell-derived cardiomyocytes is one of the most promising therapeutic approaches after myocardial infarction, as loss of cardiomyocytes is virtually irreversible by endogenous repair mechanisms. In myocardial scars, transplanted cardiomyocytes will be in immediate contact with cardiac fibroblasts. While it is well documented how the electrophysiology of neonatal cardiomyocytes is modulated by cardiac fibroblasts of the same developmental stage, it is unknown how adult cardiac fibroblasts (aCFs) affect the function of embryonic stem cell-derived cardiomyocytes (ESC-CMs). To investigate the effects of aCFs on ESC-CM electrophysiology, we performed extra- and intracellular recordings of murine aCF-ESC-CM cocultures. We observed that spontaneous beating behaviour was highly irregular in aCF-ESC-CM cocultures compared to cocultures with mesenchymal stem cells (coefficient of variation of the interspike interval: 40.5 ± 15.2% versus 9.3 ± 2.0%, p = 0.008) and that action potential amplitude and maximal upstroke velocity (V max) were reduced (amplitude: 52.3 ± 1.7 mV versus 65.1 ± 1.5 mV, V max: 7.0 ± 1.0 V/s versus 36.5 ± 5.3 V/s), while action potential duration (APD) was prolonged (APD50: 25.6 ± 1.0 ms versus 16.8 ± 1.9 ms, p < 0.001; APD90: 52.2 ± 1.5 ms versus 43.3 ± 3.3 ms, p < 0.01) compared to controls. Similar changes could be induced by aCF-conditioned medium. We conclude that the presence of aCFs changes automaticity and induces potentially proarrhythmic changes of ESC-CM electrophysiology.

Treatment of allergic rhinitis and urticaria: a review of the newest antihistamine drug bilastine

PubMed Central

Wang, Xue Yan; Lim-Jurado, Margaret; Prepageran, Narayanan; Tantilipikorn, Pongsakorn; Wang, De Yun

2016-01-01

Allergic rhinitis and urticaria are common allergic diseases that may have a major negative impact on patients’ quality of life. Bilastine, a novel new-generation antihistamine that is highly selective for the H1 histamine receptor, has a rapid onset and prolonged duration of action. This agent does not interact with the cytochrome P450 system and does not undergo significant metabolism in humans, suggesting that it has very low potential for drug–drug interactions, and does not require dose adjustment in renal impairment. As bilastine is not metabolized and is excreted largely unchanged, hepatic impairment is not expected to increase systemic exposure above the drug’s safety margin. Bilastine has demonstrated similar efficacy to cetirizine and desloratadine in patients with seasonal allergic rhinitis and, in a Vienna Chamber study, a potentially longer duration of action than fexofenadine in patients with asymptomatic seasonal allergic rhinitis. It has also shown significant efficacy (similar to that of cetirizine) and safety in the long-term treatment of perennial allergic rhinitis. Bilastine showed similar efficacy to levocetirizine in patients with chronic spontaneous urticaria and can be safely used at doses of up to fourfold higher than standard dosage (80 mg once daily). The fourfold higher than standard dose is specified as an acceptable second-line treatment option for urticaria in international guidelines. Bilastine is generally well tolerated, both at standard and at supratherapeutic doses, appears to have less sedative potential than other second-generation antihistamines, and has no cardiotoxicity. Based on its pharmacokinetic properties, efficacy, and tolerability profile, bilastine will be valuable in the management of allergic rhinitis and urticaria. PMID:27110120

Computational Modeling Reveals Key Contributions of KCNQ and hERG Currents to the Malleability of Uterine Action Potentials Underpinning Labor

PubMed Central

Tong, Wing-Chiu; Tribe, Rachel M.; Smith, Roger; Taggart, Michael J.

2014-01-01

The electrical excitability of uterine smooth muscle cells is a key determinant of the contraction of the organ during labor and is manifested by spontaneous, periodic action potentials (APs). Near the end of term, APs vary in shape and size reflecting an ability to change the frequency, duration and amplitude of uterine contractions. A recent mathematical model quantified several ionic features of the electrical excitability in uterine smooth muscle cells. It replicated many of the experimentally recorded uterine AP configurations but its limitations were evident when trying to simulate the long-duration bursting APs characteristic of labor. A computational parameter search suggested that delayed rectifying K+ currents could be a key model component requiring improvement to produce the longer-lasting bursting APs. Of the delayed rectifying K+ currents family it is of interest that KCNQ and hERG channels have been reported to be gestationally regulated in the uterus. These currents exhibit features similar to the broadly defined uterine I K1 of the original mathematical model. We thus formulated new quantitative descriptions for several I KCNQ and I hERG. Incorporation of these currents into the uterine cell model enabled simulations of the long-lasting bursting APs. Moreover, we used this modified model to simulate the effects of different contributions of I KCNQ and I hERG on AP form. Our findings suggest that the alterations in expression of hERG and KCNQ channels can potentially provide a mechanism for fine tuning of AP forms that lends a malleability for changing between plateau-like and long-lasting bursting-type APs as uterine cells prepare for parturition. PMID:25474527

Glycogen synthase kinase 3 beta alters anxiety-, depression-, and addiction-related behaviors and neuronal activity in the nucleus accumbens shell

PubMed Central

Crofton, Elizabeth J.; Nenov, Miroslav N.; Zhang, Yafang; Scala, Federico; Page, Sean A.; McCue, David L.; Li, Dingge; Hommel, Jonathan D.; Laezza, Fernanda; Green, Thomas A.

2017-01-01

Psychiatric disorders such as anxiety, depression and addiction are often comorbid brain pathologies thought to share common mechanistic biology. As part of the cortico-limbic circuit, the nucleus accumbens shell (NAcSh) plays a fundamental role in integrating information in the circuit, such that modulation of NAcSh circuitry alters anxiety, depression, and addiction-related behaviors. Intracellular kinase cascades in the NAcSh have proven important mediators of behavior. To investigate glycogen-synthase kinase 3 (GSK3) beta signaling in the NAcSh in vivo we knocked down GSK3beta expression with a novel adeno-associated viral vector (AAV2) and assessed changes in anxiety- and depression-like behavior and cocaine self-administration in GSK3beta knockdown rats. GSK3beta knockdown reduced anxiety-like behavior while increasing depression-like behavior and cocaine self-administration. Correlative electrophysiological recordings in acute brain slices were used to assess the effect of AAV-shGSK3beta on spontaneous firing and intrinsic excitability of tonically active interneurons (TANs), cells required for input and output signal integration in the NAcSh and for processing reward-related behaviors. Loose-patch recordings showed that TANs transduced by AAV-shGSK3beta exhibited reduction in tonic firing and increased spike half width. When assessed by whole-cell patch clamp recordings these changes were mirrored by reduction in action potential firing and accompanied by decreased hyperpolarization-induced depolarizing sag potentials, increased action potential current threshold, and decreased maximum rise time. These results suggest that silencing of GSK3beta in the NAcSh increases depression- and addiction-related behavior, possibly by decreasing intrinsic excitability of TANs. However, this study does not rule out contributions from other neuronal sub-types. PMID:28126496

Menthol enhances phasic and tonic GABAA receptor-mediated currents in midbrain periaqueductal grey neurons

PubMed Central

Lau, Benjamin K; Karim, Shafinaz; Goodchild, Ann K; Vaughan, Christopher W; Drew, Geoffrey M

2014-01-01

Background and Purpose Menthol, a naturally occurring compound in the essential oil of mint leaves, is used for its medicinal, sensory and fragrant properties. Menthol acts via transient receptor potential (TRPM8 and TRPA1) channels and as a positive allosteric modulator of recombinant GABAA receptors. Here, we examined the actions of menthol on GABAA receptor-mediated currents in intact midbrain slices. Experimental Approach Whole-cell voltage-clamp recordings were made from periaqueductal grey (PAG) neurons in midbrain slices from rats to determine the effects of menthol on GABAA receptor-mediated phasic IPSCs and tonic currents. Key Results Menthol (150–750 μM) produced a concentration-dependent prolongation of spontaneous GABAA receptor-mediated IPSCs, but not non-NMDA receptor-mediated EPSCs throughout the PAG. Menthol actions were unaffected by TRPM8 and TRPA1 antagonists, tetrodotoxin and the benzodiazepine antagonist, flumazenil. Menthol also enhanced a tonic current, which was sensitive to the GABAA receptor antagonists, picrotoxin (100 μM), bicuculline (30 μM) and Zn2+ (100 μM), but unaffected by gabazine (10 μM) and a GABAC receptor antagonist, 1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA; 50 μM). In addition, menthol potentiated currents induced by the extrasynaptic GABAA receptor agonist THIP/gaboxadol (10 μM). Conclusions and Implications These results suggest that menthol positively modulates both synaptic and extrasynaptic populations of GABAA receptors in native PAG neurons. The development of agents that potentiate GABAA-mediated tonic currents and phasic IPSCs in a manner similar to menthol could provide a basis for novel GABAA-related pharmacotherapies. PMID:24460753

Stationary and non-stationary occurrences of miniature end plate potentials are well described as stationary and non-stationary Poisson processes in the mollusc Navanax inermis.

PubMed

Cappell, M S; Spray, D C; Bennett, M V

1988-06-28

Protractor muscles in the gastropod mollusc Navanax inermis exhibit typical spontaneous miniature end plate potentials with mean amplitude 1.71 +/- 1.19 (standard deviation) mV. The evoked end plate potential is quantized, with a quantum equal to the miniature end plate potential amplitude. When their rate is stationary, occurrence of miniature end plate potentials is a random, Poisson process. When non-stationary, spontaneous miniature end plate potential occurrence is a non-stationary Poisson process, a Poisson process with the mean frequency changing with time. This extends the random Poisson model for miniature end plate potentials to the frequently observed non-stationary occurrence. Reported deviations from a Poisson process can sometimes be accounted for by the non-stationary Poisson process and more complex models, such as clustered release, are not always needed.

Greenhouse gas emissions from Australian open-cut coal mines: contribution from spontaneous combustion and low-temperature oxidation.

PubMed

Day, Stuart J; Carras, John N; Fry, Robyn; Williams, David J

2010-07-01

Spontaneous combustion and low-temperature oxidation of waste coal and other carbonaceous material at open-cut coal mines are potentially significant sources of greenhouse gas emissions. However, the magnitude of these emissions is largely unknown. In this study, emissions from spontaneous combustion and low-temperature oxidation were estimated for six Australian open-cut coal mines with annual coal production ranging from 1.7 to more than 16 Mt. Greenhouse emissions from all other sources at these mines were also estimated and compared to those from spontaneous combustion and low-temperature oxidation. In all cases, fugitive emission of methane was the largest source of greenhouse gas; however, in some mines, spontaneous combustion accounted for almost a third of all emissions. For one mine, it was estimated that emissions from spontaneous combustion were around 250,000 t CO(2)-e per annum. The contribution from low-temperature oxidation was generally less than about 1% of the total for all six mines. Estimating areas of spoil affected by spontaneous combustion by ground-based surveys was prone to under-report the area. Airborne infrared imaging appears to be a more reliable method.

Gauge copies in the Landau-DeWitt gauge: A background invariant restriction

NASA Astrophysics Data System (ADS)

Dudal, David; Vercauteren, David

2018-04-01

The Landau background gauge, also known as the Landau-DeWitt gauge, has found renewed interest during the past decade given its usefulness in accessing the confinement-deconfinement transition via the vacuum expectation value of the Polyakov loop, describable via an appropriate background. In this Letter, we revisit this gauge from the viewpoint of it displaying gauge (Gribov) copies. We generalize the Gribov-Zwanziger effective action in a BRST and background invariant way; this action leads to a restriction on the allowed gauge fluctuations, thereby eliminating the infinitesimal background gauge copies. The explicit background invariance of our action is in contrast with earlier attempts to write down and use an effective Gribov-Zwanziger action. It allows to address certain subtleties arising in these earlier works, such as a spontaneous and thus spurious Lorentz symmetry breaking, something which is now averted.

Symmetry breaking in holographic theories with Lifshitz scaling

NASA Astrophysics Data System (ADS)

Argurio, Riccardo; Hartong, Jelle; Marzolla, Andrea; Naegels, Daniel

2018-02-01

We study holographically Lifshitz-scaling theories with broken symmetries. In order to do this, we set up a bulk action with a complex scalar and a massless vector on a background which consists in a Lifshitz metric and a massive vector. We first study separately the complex scalar and the massless vector, finding a similar pattern in the twopoint functions that we can compute analytically. By coupling the probe complex scalar to the background massive vector we can construct probe actions that are more general than the usual Klein-Gordon action. Some of these actions have Galilean boost symmetry. Finally, in the presence of a symmetry breaking scalar profile in the bulk, we reproduce the expected Ward identities of a Lifshitz-scaling theory with a broken global continuous symmetry. In the spontaneous case, the latter imply the presence of a gapless mode, the Goldstone boson, which will have dispersion relations dictated by the Lifshitz scaling.

Young Children See a Single Action and Infer a Social Norm.

PubMed

Schmidt, Marco F H; Butler, Lucas P; Heinz, Julia; Tomasello, Michael

2016-10-01

Human social life depends heavily on social norms that prescribe and proscribe specific actions. Typically, young children learn social norms from adult instruction. In the work reported here, we showed that this is not the whole story: Three-year-old children are promiscuous normativists. In other words, they spontaneously inferred the presence of social norms even when an adult had done nothing to indicate such a norm in either language or behavior. And children of this age even went so far as to enforce these self-inferred norms when third parties "broke" them. These results suggest that children do not just passively acquire social norms from adult behavior and instruction; rather, they have a natural and proactive tendency to go from "is" to "ought." That is, children go from observed actions to prescribed actions and do not perceive them simply as guidelines for their own behavior but rather as objective normative rules applying to everyone equally.

Ajmaline blocks INa and IKr without eliciting differences between Brugada syndrome patient and control human pluripotent stem cell-derived cardiac clusters.

PubMed

Miller, Duncan C; Harmer, Stephen C; Poliandri, Ariel; Nobles, Muriel; Edwards, Elizabeth C; Ware, James S; Sharp, Tyson V; McKay, Tristan R; Dunkel, Leo; Lambiase, Pier D; Tinker, Andrew

2017-12-01

The class Ia anti-arrhythmic drug ajmaline is used clinically to unmask latent type I ECG in Brugada syndrome (BrS) patients, although its mode of action is poorly characterised. Our aims were to identify ajmaline's mode of action in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs), and establish a simple BrS hiPSC platform to test whether differences in ajmaline response could be determined between BrS patients and controls. Control hiPSCs were differentiated into spontaneously contracting cardiac clusters. It was found using multi electrode array (MEA) that ajmaline treatment significantly lengthened cluster activation-recovery interval. Patch clamping of single CMs isolated from clusters revealed that ajmaline can block both I Na and I Kr . Following generation of hiPSC lines from BrS patients (absent of pathogenic SCN5A sodium channel mutations), analysis of hiPSC-CMs from patients and controls revealed that differentiation and action potential parameters were similar. Comparison of cardiac clusters by MEA showed that ajmaline lengthened activation-recovery interval consistently across all lines. We conclude that ajmaline can block both depolarisation and repolarisation of hiPSC-CMs at the cellular level, but that a more refined integrated tissue model may be necessary to elicit differences in its effect between BrS patients and controls. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Spontaneous transformation of adult mesenchymal stem cells from cynomolgus macaques in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ren, Zhenhua; Key Laboratory of Neurodegeneration, Ministry of Education, Beijing; Department of Anatomy, Anhui Medical University, Hefei, 230032

2011-12-10

Mesenchymal stem cells (MSCs) have shown potential clinical utility in cell therapy and tissue engineering, due to their ability to proliferate as well as to differentiate into multiple lineages, including osteogenic, adipogenic, and chondrogenic specifications. Therefore, it is crucial to assess the safety of MSCs while extensive expansion ex vivo is a prerequisite to obtain the cell numbers for cell transplantation. Here we show that MSCs derived from adult cynomolgus monkey can undergo spontaneous transformation following in vitro culture. In comparison with MSCs, the spontaneously transformed mesenchymal cells (TMCs) display significantly different growth pattern and morphology, reminiscent of the characteristicsmore » of tumor cells. Importantly, TMCs are highly tumorigenic, causing subcutaneous tumors when injected into NOD/SCID mice. Moreover, no multiple differentiation potential of TMCs is observed in vitro or in vivo, suggesting that spontaneously transformed adult stem cells may not necessarily turn into cancer stem cells. These data indicate a direct transformation of cynomolgus monkey MSCs into tumor cells following long-term expansion in vitro. The spontaneous transformation of the cultured cynomolgus monkey MSCs may have important implications for ongoing clinical trials and for models of oncogenesis, thus warranting a more strict assessment of MSCs prior to cell therapy. -- Highlights: Black-Right-Pointing-Pointer Spontaneous transformation of cynomolgus monkey MSCs in vitro. Black-Right-Pointing-Pointer Transformed mesenchymal cells lack multipotency. Black-Right-Pointing-Pointer Transformed mesenchymal cells are highly tumorigenic. Black-Right-Pointing-Pointer Transformed mesenchymal cells do not have the characteristics of cancer stem cells.« less

Malignant Transformation Potentials of Human Umbilical Cord Mesenchymal Stem Cells Both Spontaneously and via 3-Methycholanthrene Induction

PubMed Central

Lai, Xiulan; Liu, Sizheng; Chen, Yezeng; Zheng, Zexin; Xie, Qingdong; Maldonado, Martin; Cai, Zhiwei; Qin, Shan; Ho, Guyu; Ma, Lian

2013-01-01

Human umbilical cord mesenchymal stem cells (HUMSCs) are highly proliferative and can be induced to differentiate into advanced derivatives of all three germ layers. Thus, HUMSCs are considered to be a promising source for cell-targeted therapies and tissue engineering. However there are reports on spontaneous transformation of mesenchymal stem cells (MSCs) derived from human bone marrows. The capacity for HUMSCs to undergo malignant transform spontaneously or via induction by chemical carcinogens is presently unknown. Therefore, we isolated HUMSCs from 10 donors and assessed their transformation potential either spontaneously or by treating them with 3-methycholanthrene (3-MCA), a DNA-damaging carcinogen. The malignant transformation of HUMSCs in vitro was evaluated by morphological changes, proliferation rates, ability to enter cell senescence, the telomerase activity, chromosomal abnormality, and the ability to form tumors in vivo. Our studies showed that HUMSCs from all 10 donors ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUMSCs from two of the 10 donors treated with 3-MCA displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. When these cells (tHUMSCs) were injected into immunodeficient mice, they gave rise to sarcoma-like or poorly differentiated tumors. Moreover, in contrast to HUMSCs, tHUMSCs showed a positive expression of human telomerase reverse transcriptase (hTERT) and did not exhibit a shortening of the relative telomere length during the long-term culture in vitro. Our studies demonstrate that HUMSCs are not susceptible to spontaneous malignant transformation. However, the malignant transformation could be induced by chemical carcinogen 3-MCA. PMID:24339974

Epileptiform activity induced by lowering extracellular [Mg2+] in combined hippocampal-entorhinal cortex slices: modulation by receptors for norepinephrine and N-methyl-D-aspartate.

PubMed

Stanton, P K; Jones, R S; Mody, I; Heinemann, U

1987-01-01

Reduction of extracellular Mg2+ concentration induced spontaneous and evoked epileptiform activity in the entorhinal cortex (EC) and dentate gyrus (DG) of combined hippocampus (HC)-EC slices. Extracellular field potentials, as well as changes in extracellular Ca2+ and K+ concentrations, were measured in EC and DG with ion-selective/reference electrodes during both repetitive and single stimuli. In the EC, lowering extracellular [Mg2+] induces both spontaneous and single stimulus evoked ictal events consisting of extracellular negative potential shifts (up to 5 mV, 30 sec), decreases in [Ca2+]0 and increases in [K+]0. In the DG, spontaneous events were much shorter, but similar changes in [Ca2+]0, [K+]0 and field potentials (FPs) could be evoked by brief high-frequency stimulation. In both areas, the N-methyl-D-aspartate (NMDA) receptor antagonist 2-aminophosphonovalerate (2-APV) completely blocked spontaneous as well as stimulus evoked epileptiform events. The neurotransmitter norepinephrine (NE), which has previously been shown to modulate long-term potentiation in the DG, was found to exhibit differential modulation of epileptiform activity in the EC and DG. In the EC, NE, acting via alpha 1-receptors, completely blocked low Mg2+-induced epileptiform activity. In contrast, in the DG, NE exhibited a beta-receptor mediated prolongation of the low Mg2+-induced ictal events, and enhanced the stimulus-induced ionic and field potential changes. From these results, we conclude that lowering extracellular [Mg2+], acting in large part through the removal of the Mg2+ voltage-dependent blockade of NMDA receptors, leads to induction of epileptiform activity in both the EC and DG.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Antiepileptic Drugs on Spontaneous Recurrent Seizures in a Novel Model of Extended Hippocampal Kindling in Mice

PubMed Central

Song, Hongmei; Tufa, Uilki; Chow, Jonathan; Sivanenthiran, Nila; Cheng, Chloe; Lim, Stellar; Wu, Chiping; Feng, Jiachun; Eubanks, James H.; Zhang, Liang

2018-01-01

Epilepsy is a common neurological disorder characterized by naturally-occurring spontaneous recurrent seizures and comorbidities. Kindling has long been used to model epileptogenic mechanisms and to assess antiepileptic drugs. In particular, extended kindling can induce spontaneous recurrent seizures without gross brain lesions, as seen clinically. To date, the development of spontaneous recurrent seizures following extended kindling, and the effect of the antiepileptic drugs on these seizures are not well understood. In the present study we aim to develop a mouse model of extended hippocampal kindling for the first time. Once established, we plan to evaluate the effect of three different antiepileptic drugs on the development of the extended-hippocampal-kindled-induced spontaneous recurrent seizures. Male C57 black mice were used for chronic hippocampal stimulations or handling manipulations (twice daily for up to 70 days). Subsequently, animals underwent continuous video/EEG monitoring for seizure detection. Spontaneous recurrent seizures were consistently observed in extended kindled mice but no seizures were detected in the control animals. The aforementioned seizures were generalized events characterized by hippocampal ictal discharges and concurrent motor seizures. Incidence and severity of the seizures was relatively stable while monitored over a few months after termination of the hippocampal stimulation. Three antiepileptic drugs with distinct action mechanisms were tested: phenytoin, lorazepam and levetiracetam. They were applied via intra-peritoneal injections at anticonvulsive doses and their effects on the spontaneous recurrent seizures were analyzed 10–12 h post-injection. Phenytoin (25 mg/kg) and levetiracetam (400 mg/kg) abolished the spontaneous recurrent seizures. Lorazepam (1.5 mg/kg) decreased motor seizure severity but did not reduce the incidence and duration of corresponding hippocampal discharges, implicating its inhibitory effects on seizure spread. No gross brain lesions were observed in a set of extended hippocampal kindled mice submitted to histological evaluation. All these data suggests that our model could be considered as a novel mouse model of extended hippocampal kindling. Some limitations remain to be considered. PMID:29867462

The membrane-stabilizing action of zinc carnosine (Z-103) in stress-induced gastric ulceration in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cho, C.H.; Luk, C.T.; Ogle, C.W.

1991-01-01

Zinc compounds have been shown to antagonize various types of gastric ulceration in rats. Zinc carnosine (Z-103), a newly developed agent was, therefore, examined for its antiulcer effect in stress-induced ulceration and also its membrane stabilizing action in rat stomachs. Cold-restraint stress induced severe hemorrhagic lesions together with increased mast cell degranulation and {beta}-glucuronidase release in the gastric glandular mucosa. A-103 pretreatment with a single oral dose reversed these actions in a dose-dependent manner. When the compound was incubated in concentrations of 10{sup {minus}7}, 10{sup {minus}6}, 10{sup {minus}5} or 10{sup {minus}4} M, with isolated hepatic lysosomes, it significantly reduced themore » spontaneous release of {beta}-glucuronidase in the medium. The present study not only demonstrates the antiulcer effect of Z-103 but also indicates that the protective action is likely to be mediated by its membrane-stabilizing action on mast cells and lysosomes in the gastric glandular mucosa.« less

Neuroprotective effects of vinpocetine and its major metabolite cis-apovincaminic acid on NMDA-induced neurotoxicity in a rat entorhinal cortex lesion model.

PubMed

Nyakas, Csaba; Felszeghy, Klára; Szabó, Róbert; Keijser, Jan N; Luiten, Paul G M; Szombathelyi, Zsolt; Tihanyi, Károly

2009-01-01

Vinpocetine (ethyl-apovincaminate, Cavinton), a synthetic derivative of the Vinca minor alkaloid vincamine, has been used now for decades for prevention and treatment of cerebrovascular diseases predisposing to development of dementia. Both vinpocetine and its main metabolite cis-apovincaminic acid (cAVA) exert a neuroprotective type of action. Bilateral N-methyl-D-aspartate (NMDA)-induced neurodegeneration in the entorhinal cortex of rat was used as a dementia model to confirm the neuroprotective action of these compounds in vivo. NMDA-lesioned rats were treated 60 min before lesion and throughout 3 postoperative days with a 10 mg/kg intraperitoneal dose of vinpocetine or cAVA. Behavioral tests started after termination of drug treatment and consisted of novel object recognition, social discrimination, and spontaneous alternation in a Y-maze, and spatial learning in the Morris water maze. At the end of behavioral testing brains were perfused with fixative and the size of the excitotoxic neuronal lesion and that of microglial activation around the lesion were assayed quantitatively on brain sections immunostained for neuron-specific nuclear protein (NeuN) and integrin CD11b, respectively. Entorhinal NMDA lesions impaired recognition of novel objects and the new social partner, and suppressed spontaneous alternation and spatial learning performance in the Morris maze. Both vinpocetine and cAVA effectively attenuated the behavioral deficits, and significantly decreased lesion size and the region of microglia activation. Both lesion-induced attention deficit and learning disabilities were markedly alleviated by vinpocetine and cAVA. The morphological findings corroborated the behavioral observations and indicated reduced lesion size and microglia activation especially after vinpocetine treatment which supports an in vivo neuroprotective mode of action of vinpocitine and a less potent action of cAVA.

Ce que peut la sociologie.

PubMed

Lahire, Bernard

2017-08-01

When it is relational, processual, and it articulates the incorporated dispositions of the actors and the contexts of their actions, sociology "desevidentialize," denaturalize, desubstantialize, and historicize the social world by contributing to do away with spontaneous representations that distort the reality of things. Besides, when sociology studies the social at the level of the individuals and individual actions, it destroys the fictions (juridical and philosophical) of the isolated individuals, enclosed on himself, free and fully conscious of everything. By producing images of the real state of the social world, sociology fully participates in the democratic life of our societies and should, therefore, be at the heart of the formation of citizens. Lorsqu'elle est relationnelle, processuelle, et qu'elle articule les dispositions incorporées des acteurs et les contextes de leurs actions, la sociologie 'désévidentialise', dénaturalise, désubstantialise et historicise le monde social en contribuant à chasser les représentations spontanées qui déforment la réalité des choses. Lorsque, par ailleurs, elle étudie le social à l'échelle des individus et des actions individuelles, elle détruit les fictions (juridique comme philosophique) de l'individu isolé, enfermé sur lui-même, libre et pleinement conscient de tout. Produisant des images un tant soit peu précises et justes de l'état réel du monde social, la sociologie participe pleinement à la vie démocratique de nos sociétés et devrait, pour cette raison, être au cœur de la formation des citoyens. © 2017 Canadian Sociological Association/La Société canadienne de sociologie.

Preclinical pharmacology of midazolam.

PubMed

Pieri, L

1983-01-01

Midazolam, a new imidazobenzodiazepine, forms salts that are stable in water solution, and has an overall pharmacological potency similar to that of diazepam but a much shorter duration of action. It produces all the characteristic effects of the benzodiazepine class. Its metabolites account for only a negligible part, if any, of its pharmacological effects observed in the mouse. The time course of its anticonvulsant activity, studied with different experimental protocols and by different routes of administration, revealed an almost immediate onset of action. Midazolam was slightly more potent, and its duration of action was shorter than diazepam, in enhancing presynaptic inhibition in the spinal cord of cats and in depressing spontaneous activity of cerebellar Purkinje cells in the rat. Midazolam decreased spontaneous multiunit activity (MUA) in different nuclei of the brain in 'encéphale isolé' rats. This depression was reversed by Ro 15-1788, a recently discovered selective benzodiazepine antagonist. Midazolam and diazepam decreased the cyclic GMP level in the cerebellum of rats with about the same potency; the effect of midazolam was of much shorter duration than that of diazepam. Midazolam had one-third the potency of diazepam in displacing 3H-flunitrazepam in mouse brain in vivo, and also in this case the effect of midazolam was of brief duration, as compared with diazepam. Midazolam in therapeutic doses was virtually ineffective in the cardiovascular system of conscious dogs after p.o. or i.v. administration. No direct effects of the drug on autonomic functions were found. The animal data suggest the usefulness of midazolam as an oral sleep-inducer, as an agent for i.v. induction of anaesthesia and as an i.v. or i.m. anticonvulsant in status epilepticus or tetanus, because of its rapid onset of action and its excellent local tolerance as water-soluble injection form.

Spontaneous cross-species imitation in interactions between chimpanzees and zoo visitors.

PubMed

Persson, Tomas; Sauciuc, Gabriela-Alina; Madsen, Elainie Alenkær

2018-01-01

Imitation is a cornerstone of human development, serving both a cognitive function (e.g. in the acquisition and transmission of skills and knowledge) and a social-communicative function, whereby the imitation of familiar actions serves to maintain social interaction and promote prosociality. In nonhuman primates, this latter function is poorly understood, or even claimed to be absent. In this observational study, we documented interactions between chimpanzees and zoo visitors and found that the two species imitated each other at a similar rate, corresponding to almost 10% of all produced actions. Imitation appeared to accomplish a social-communicative function, as cross-species interactions that contained imitative actions lasted significantly longer than interactions without imitation. In both species, physical proximity promoted cross-species imitation. Overall, imitative precision was higher among visitors than among chimpanzees, but this difference vanished in proximity contexts, i.e. in the indoor environment. Four of five chimpanzees produced imitations; three of them exhibited comparable imitation rates, despite large individual differences in level of cross-species interactivity. We also found that chimpanzees evidenced imitation recognition, yet only when visitors imitated their actions (as opposed to postures). Imitation recognition was expressed by returned imitation in 36% of the cases, and all four imitating chimpanzees engaged in so-called imitative games. Previously regarded as unique to early human socialization, such games serve to maintain social engagement. The results presented here indicate that nonhuman apes exhibit spontaneous imitation that can accomplish a communicative function. The study raises a number of novel questions for imitation research and highlights the imitation of familiar behaviours as a relevant-yet thus far understudied-research topic.

Burr hole drainage for complicated spontaneous intracranial hypotension syndrome.

PubMed

Liu, Yu-Fang; Lin, Hung-Lin; Cho, Der-Yang; Chen, Chun-Chung; Lo, Yu-Chien; Chiou, Shang-Ming

2008-09-01

Spontaneous intracranial hypotension is a potentially severe condition that is caused by continuous cerebrospinal fluid leakage. Clinically, most patients have a benign course and the condition remits after conservative management. We report two consecutive patients who presented with acute expansion of subdural collection and disturbed consciousness. Both patients recovered completely after undergoing burr hole drainage.

Enforced epithelial expression of IGF-1 causes hyperplastic prostate growth while negative selection is requisite for spontaneous metastogenesis

USDA-ARS?s Scientific Manuscript database

The insulin-like growth factor-1 (IGF-1) signaling axis is important for cell growth, differentiation, and survival, and increased serum IGF is a risk factor for prostate and other cancers. To study IGF-1 action on the prostate, we created transgenic (PB-Des) mice that specifically express human IGF...

Making the Implicit Explicit: Raising Pragmatic Awareness in Trainee Interpreters Using Semiauthentic Spontaneous Discourse Samples

ERIC Educational Resources Information Center

Sachtleben, Annette; Denny, Heather

2012-01-01

Following the recent interest in the teaching of pragmatics and the recognition of its importance for both cross-cultural communication and new speakers of an additional language, the authors carried out an action research project to evaluate the effectiveness of a new approach to the teaching of pragmatics. This involved the use of semiauthentic…

The Nature, Meaning, and Measure of Teacher Flow in Elementary Schools: A Test of Rival Hypotheses

ERIC Educational Resources Information Center

Beard, Karen Stansberry; Hoy, Wayne K.

2010-01-01

Purpose: This inquiry is the first comprehensive, empirical analysis of the nature and measurement of flow in elementary teachers. The clearest sign of flow is the merging of action and awareness, that is, the degree to which an activity becomes spontaneous and automatic and individuals lose conscious awareness of themselves as they perform a task…

Identification of developmentally toxic drinking water disinfection byproducts and evaluation of data relevant to mode of action

DOE Office of Scientific and Technical Information (OSTI.GOV)

Colman, Joan; Rice, Glenn E., E-mail: rice.glenn@epa.gov; Wright, J. Michael

Reactions between chemicals used to disinfect drinking water and compounds present in source waters produce chemical mixtures containing hundreds of disinfection byproducts (DBPs). Although the results have been somewhat inconsistent, some epidemiological studies suggest associations may exist between DBP exposures and adverse developmental outcomes. The potencies of individual DBPs in rodent and rabbit developmental bioassays suggest that no individual DBP can account for the relative risk estimates reported in the positive epidemiologic studies, leading to the hypothesis that these outcomes could result from the toxicity of DBP mixtures. As a first step in a mixtures risk assessment for DBP developmentalmore » effects, this paper identifies developmentally toxic DBPs and examines data relevant to the mode of action (MOA) for DBP developmental toxicity. We identified 24 developmentally toxic DBPs and four adverse developmental outcomes associated with human DBP exposures: spontaneous abortion, cardiovascular defects, neural tube defects, and low birth weight infancy. A plausible MOA, involving hormonal disruption of pregnancy, is delineated for spontaneous abortion, which some epidemiologic studies associate with total trihalomethane and bromodichloromethane exposures. The DBP data for the other three outcomes were inadequate to define key MOA steps.« less

Gynaecomastia--pathophysiology, diagnosis and treatment.

PubMed

Narula, Harmeet S; Carlson, Harold E

2014-11-01

Gynaecomastia (enlargement of the male breast tissue) is a common finding in the general population. Most cases of gynaecomastia are benign and of cosmetic, rather than clinical, importance. However, the condition might cause local pain and tenderness, could occasionally be the result of a serious underlying illness or a medication, or be inherited. Breast cancer in men is much less common than benign gynaecomastia, and the two conditions can usually be distinguished by a careful physical examination. Estrogens are known to stimulate the growth of breast tissue, whereas androgens inhibit it; most cases of gynaecomastia result from deficient androgen action or excessive estrogen action in the breast tissue. In some cases, such as pubertal gynaecomastia, the breast enlargement resolves spontaneously. In other situations, more active treatment might be required to correct an underlying condition (such as hyperthyroidism or a benign Leydig cell tumour of the testis) or medications that could cause breast enlargement (such as spironolactone) might need to be discontinued. For men with hypogonadism, administration of androgens might be helpful, as might antiestrogen therapy in men with endogenous overproduction of estrogens. Surgery to remove the enlarged breast tissue might be necessary when gynaecomastia does not resolve spontaneously or with medical therapy.

Magnetite-Amyloid-β deteriorates activity and functional organization in an in vitro model for Alzheimer’s disease

NASA Astrophysics Data System (ADS)

Teller, Sara; Tahirbegi, Islam Bogachan; Mir, Mònica; Samitier, Josep; Soriano, Jordi

2015-11-01

The understanding of the key mechanisms behind human brain deterioration in Alzheimer’ disease (AD) is a highly active field of research. The most widespread hypothesis considers a cascade of events initiated by amyloid-β peptide fibrils that ultimately lead to the formation of the lethal amyloid plaques. Recent studies have shown that other agents, in particular magnetite, can also play a pivotal role. To shed light on the action of magnetite and amyloid-β in the deterioration of neuronal circuits, we investigated their capacity to alter spontaneous activity patterns in cultured neuronal networks. Using a versatile experimental platform that allows the parallel monitoring of several cultures, the activity in controls was compared with the one in cultures dosed with magnetite, amyloid-β and magnetite-amyloid-β complex. A prominent degradation in spontaneous activity was observed solely when amyloid-β and magnetite acted together. Our work suggests that magnetite nanoparticles have a more prominent role in AD than previously thought, and may bring new insights in the understanding of the damaging action of magnetite-amyloid-β complex. Our experimental system also offers new interesting perspectives to explore key biochemical players in neurological disorders through a controlled, model system manner.

The role of IL-6 and IL-1beta in painful perineural inflammatory neuritis.

PubMed

Eliav, Eli; Benoliel, Rafael; Herzberg, Uri; Kalladka, Mythili; Tal, Michael

2009-05-01

Inflammation along a nerve trunk (perineural inflammation), without detectable axonal damage, has been shown to induce transient pain in the organ supplied by the nerve. The aims of the present study were to study the role IL-6 and IL-1beta, in pain induced by perineural inflammation. IL-6 and IL-1beta secretion from rat's sciatic nerves, L-5 Dorsal Root Ganglia (DRG), and the hind paw skin, 3 and 8 days following exposure of the nerve to Complete Freund's Adjuvant (CFA), were measured using ELISA method. Hind paw tactile-allodynia, mechano-hyperalgesia, heat-allodynia and electrical detection thresholds were tested up to 8 days following the application of CFA, IL-6 or IL-1beta adjacent to the sciatic nerve trunk. Employing electrophysiological recording, saphenous nerve spontaneous activity, nerve trunk mechano-sensitivity and paw tactile detection threshold (determined by recording action potential induced by the lowest mechanical stimulus) were assessed 3 and 8 days following exposure of the nerve trunk to CFA, IL-6, or IL-1beta. IL-6 and IL-1beta secretion from the nerve was significantly elevated on the 3rd day post-operation (DPO). On the 8th DPO, IL-6 levels returned to baseline while IL-1beta levels remained significantly elevated. The DRG cytokine's level was increased on the 3rd and 8th DPOs, contralateral cytokine's level was increased on the 3rd DPO. The skin IL-6 level was increased bilaterally on the 3rd DPO and returned to baseline on the 8th DPO. IL-1beta levels increased in the affected side on the 3rd and bilaterally on the 8th DPO. Direct application of IL-6 or CFA on the sciatic nerve induced significant hind paw tactile-allodynia from the 1st to 5th DPOs, reduced electrical detection threshold from the 1st to 3rd DPOs, mechano-hyperalgesia from 3rd to 5th DPOs and heat-allodynia on the 3rd DPO. Direct application of IL-1beta induced paw tactile and heat-allodynia on the 7-8th DPOs and mechano-hyperalgesia on the 5-8th DPOs. Perineural inflammation significantly increased spontaneous activity myelinated fibres 3 and 8 days following the application. Direct application of IL-6 induced elevation of spontaneous activity on the 3rd while IL-1beta on the 8th DPO. Nerve mechano-sensitivity was significantly increased on the 3rd day following exposure to CFA and IL-6 and on the 8th following CFA application. The rat's paw lowest mechanical force necessary for induction of action potential, was significantly reduced 3 days following CFA application. IL-6 and IL-1beta play an important role in pain induced by perineural inflammation. IL-6 activity is more prominent immediately following application (2-5th DPOs), while IL-1beta, activity is more significant in a later stage (5-8th DPOs).

Canine spontaneous glioma: A translational model system for convection-enhanced delivery

PubMed Central

Dickinson, Peter J.; LeCouteur, Richard A.; Higgins, Robert J.; Bringas, John R.; Larson, Richard F.; Yamashita, Yoji; Krauze, Michal T.; Forsayeth, John; Noble, Charles O.; Drummond, Daryl C.; Kirpotin, Dmitri B.; Park, John W.; Berger, Mitchel S.; Bankiewicz, Krystof S.

2010-01-01

Canine spontaneous intracranial tumors bear striking similarities to their human tumor counterparts and have the potential to provide a large animal model system for more realistic validation of novel therapies typically developed in small rodent models. We used spontaneously occurring canine gliomas to investigate the use of convection-enhanced delivery (CED) of liposomal nanoparticles, containing topoisomerase inhibitor CPT-11. To facilitate visualization of intratumoral infusions by real-time magnetic resonance imaging (MRI), we included identically formulated liposomes loaded with Gadoteridol. Real-time MRI defined distribution of infusate within both tumor and normal brain tissues. The most important limiting factor for volume of distribution within tumor tissue was the leakage of infusate into ventricular or subarachnoid spaces. Decreased tumor volume, tumor necrosis, and modulation of tumor phenotype correlated with volume of distribution of infusate (Vd), infusion location, and leakage as determined by real-time MRI and histopathology. This study demonstrates the potential for canine spontaneous gliomas as a model system for the validation and development of novel therapeutic strategies for human brain tumors. Data obtained from infusions monitored in real time in a large, spontaneous tumor may provide information, allowing more accurate prediction and optimization of infusion parameters. Variability in Vd between tumors strongly suggests that real-time imaging should be an essential component of CED therapeutic trials to allow minimization of inappropriate infusions and accurate assessment of clinical outcomes. PMID:20488958

Self-bridging of vertical silicon nanowires and a universal capacitive force model for spontaneous attraction in nanostructures.

PubMed

Sun, Zhelin; Wang, Deli; Xiang, Jie

2014-11-25

Spontaneous attractions between free-standing nanostructures have often caused adhesion or stiction that affects a wide range of nanoscale devices, particularly nano/microelectromechanical systems. Previous understandings of the attraction mechanisms have included capillary force, van der Waals/Casimir forces, and surface polar charges. However, none of these mechanisms universally applies to simple semiconductor structures such as silicon nanowire arrays that often exhibit bunching or adhesions. Here we propose a simple capacitive force model to quantitatively study the universal spontaneous attraction that often causes stiction among semiconductor or metallic nanostructures such as vertical nanowire arrays with inevitably nonuniform size variations due to fabrication. When nanostructures are uniform in size, they share the same substrate potential. The presence of slight size differences will break the symmetry in the capacitive network formed between the nanowires, substrate, and their environment, giving rise to electrostatic attraction forces due to the relative potential difference between neighboring wires. Our model is experimentally verified using arrays of vertical silicon nanowire pairs with varied spacing, diameter, and size differences. Threshold nanowire spacing, diameter, or size difference between the nearest neighbors has been identified beyond which the nanowires start to exhibit spontaneous attraction that leads to bridging when electrostatic forces overcome elastic restoration forces. This work illustrates a universal understanding of spontaneous attraction that will impact the design, fabrication, and reliable operation of nanoscale devices and systems.

How often are thoughts metacognitive? Findings from research on self-regulated learning, think-aloud protocols, and mind-wandering.

PubMed

Jordano, Megan L; Touron, Dayna R

2018-05-31

Metacognitive monitoring refers to how people evaluate their cognitive performance. An extensive literature examines how accurately individuals engage in monitoring. The question of how often individuals engage in metacognitive monitoring has been largely neglected, although one might expect situational, group, and individual variability in monitoring frequency. We argue that this is a critical omission, given that the frequency of metacognitive monitoring might have important implications for monitoring accuracy and task performance. Within this review, we highlight findings from three literatures, that each provide insight into how often individuals engage in monitoring. To clarify the important links and potential overlaps between these separate bodies of research, we begin by summarizing the metacognitive monitoring literature, including age-related patterns in monitoring accuracy. We then connect these questions regarding spontaneous monitoring, including age-related patterns in spontaneous monitoring, to targeted reviews of the self-regulated learning, think-aloud protocol, and mind-wandering literatures. We discuss situational and dispositional factors believed to influence monitoring accuracy, and propose that the same factors could potentially influence the frequency of spontaneous monitoring. Additionally, we propose that age-related increases in spontaneous monitoring (as suggested by age-related increases in TRI) may contribute to older adults' intact monitoring abilities. It is our hope that this review will encourage increased attention and research on the topic of spontaneous monitoring.

Spontaneous calcium transients in human neural progenitor cells mediated by transient receptor potential channels.

PubMed

Morgan, Peter J; Hübner, Rayk; Rolfs, Arndt; Frech, Moritz J

2013-09-15

Calcium signals affect many developmental processes, including proliferation, migration, survival, and apoptosis, processes that are of particular importance in stem cells intended for cell replacement therapies. The mechanisms underlying Ca(2+) signals, therefore, have a role in determining how stem cells respond to their environment, and how these responses might be controlled in vitro. In this study, we examined the spontaneous Ca(2+) activity in human neural progenitor cells during proliferation and differentiation. Pharmacological characterization indicates that in proliferating cells, most activity is the result of transient receptor potential (TRP) channels that are sensitive to Gd(3+) and La(3+), with the more subtype selective antagonist Ruthenium red also reducing activity, suggesting the involvement of transient receptor potential vanilloid (TRPV) channels. In differentiating cells, Gd(3+) and La(3+)-sensitive TRP channels also appear to underlie the spontaneous activity; however, no sub-type-specific antagonists had any effect. Protein levels of TRPV2 and TRPV3 decreased in differentiated cells, which is demonstrated by western blot. Thus, it appears that TRP channels represent the main route of Ca(2+) entry in human neural progenitor cells (hNPCs), but the responsible channel types are subject to substitution under differentiating conditions. The level of spontaneous activity could be increased and decreased by lowering and raising the extracellular K(+) concentration. Proliferating cells in low K(+) slowed the cell cycle, with a disproportionate increased percentage of cells in G1 phase and a reduction in S phase. Taken together, these results suggest a link between external K(+) concentration, spontaneous Ca(2+) transients, and cell cycle distribution, which is able to influence the fate of stem and progenitor cells.

Identification of potential target genes and related regulatory transcription factors in spontaneous hairline fracture induced by hypervitaminosis A.

PubMed

Peng, Chuangang; Yang, Qi; Wei, Bo; Liu, Yong; Li, Yuxiang; Gu, Dawei; Yin, Guochao; Wang, Bo; Xu, Dehui; Zhang, Xuebing; Kong, Daliang

2017-07-01

The aim was to research the molecular changes of bone cells induced by excessive dose of vitamin A, and analyze molecular mechanism underlying spontaneous fracture. The gene expression profile of GSE29859, including 4 cortical bone marrow samples with excessive doses of Vitamin A and 4 control cortical bone marrow samples, was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DGEs) between cortical bone marrow samples and control samples were screened out and pathway enrichment analysis was undertaken. Based on the MSigDB database, the potential regulatory transcription factors (TFs) were identified. A total of 373 DEGs including 342 up- and 31 down-regulated genes were identified. These DEGs were significantly enriched in pathways of protein processing in endoplasmic reticulum, ubiquitin mediated proteolysis and glycerophospholipid metabolism. Finally, the most significant regulatory TFs were obtained, including E2F Transcription Factor 1 (E2F1), GA Binding Protein Transcription Factor (GABP), Nuclear Factor, Erythroid 2-Like 2 (NRF2) and ELK1, Member of ETS Oncogene Family (ELK1). Key TFs including E2F1, GABP, NRF2 and ELK1 and their targets genes such as Ube2d3, Uba1, Phb2 and Tomm22 may play potential key roles in spontaneous fracture induced by hypervitaminosis A. The pathways of protein processing in endoplasmic reticulum, ubiquitin mediated proteolysis and glycerophospholipid metabolism may be key mechanisms involved in spontaneous fracture induced by hypervitaminosis A. Our findings will provide new insights for the target selection in clinical application to prevent spontaneous fracture induced by hypervitaminosis A. Copyright © 2017 Elsevier Ltd. All rights reserved.

Activity in primary motor cortex during action observation covaries with subsequent behavioral changes in execution.

PubMed

Aridan, Nadav; Mukamel, Roy

2016-11-01

Observing someone else perform a movement facilitates motor planning, execution, and motor memory formation. Rate, an important feature in the execution of repeated movements, has been shown to vary following movement observation although the underlying neural mechanisms are unclear. In the current study, we examined how the rate of self-paced index finger pressing is implicitly modified following passive observation of a similar action performed at a different rate. Fifty subjects performed a finger pressing sequence with their right hand at their own pace before and after passive observation of either a 1-min video depicting the task performed at 3 Hz by someone else or a black screen. An additional set of 15 subjects performed the task in an MRI scanner. Across all 50 subjects, the spontaneous execution rate prior to video observation had a bimodal distribution with modes around 2 and 4 Hz. Following video observation, the slower subjects performed the task at an increased rate. In the 15 subjects who performed the task in the MRI scanner, we found positive correlation between fMRI signal in the left primary motor strip during passive video observation and subsequent behavioral changes in task performance rate. We conclude that observing someone else perform an action at a higher rate implicitly increases the spontaneous rate of execution, and that this implicit induction is mediated by activity in the contralateral primary motor cortex.

Stereoselective modulatory actions of oleamide on GABAA receptors and voltage-gated Na+ channels in vitro: a putative endogenous ligand for depressant drug sites in CNS

PubMed Central

Verdon, Bernard; Zheng, Jian; Nicholson, Russell A; Ganelli, C Robin; Lees, George

2000-01-01

cis-9,10-octadecenoamide (‘oleamide') accumulates in CSF on sleep deprivation. It induces sleep in animals (the trans form is inactive) but its cellular actions are poorly characterized. We have used electrophysiology in cultures from embryonic rat cortex and biochemical studies in mouse nerve preparations to address these issues. Twenty μM cis-oleamide (but not trans) reversibly enhanced GABAA currents and depressed the frequency of spontaneous excitatory and inhibitory synaptic activity in cultured networks. cis-oleamide stereoselectively blocked veratridine-induced (but not K+-induced) depolarisation of mouse synaptoneurosomes (IC50, 13.9 μM). The cis isomer stereoselectively blocked veratridine-induced (but not K+-induced) [3H]-GABA release from mouse synaptosomes (IC50, 4.6 μM). At 20 μM cis-oleamide, but not trans, produced a marked inhibition of Na+ channel-dependent rises in intrasynaptosomal Ca2+. The physiological significance of these observations was examined by isolating Na+ spikes in cultured pyramidal neurones. Sixty-four μM cis-oleamide did not significantly alter the amplitude, rate of rise or duration of unitary action potentials (1 Hz). cis-Oleamide stereoselectively suppressed sustained repetitive firing (SRF) in these cells with an EC50 of 4.1 μM suggesting a frequency- or state-dependent block of voltage-gated Na+ channels. Oleamide is a stereoselective modulator of both postsynaptic GABAA receptors and presynaptic or somatic voltage-gated Na+ channels which are crucial for synaptic inhibition and conduction. The modulatory actions are strikingly similar to those displayed by sedative or anticonvulsant barbiturates and a variety of general anaesthetics. Oleamide may represent an endogenous modulator for drug receptors and an important regulator of arousal. PMID:10694234

State-dependent, bidirectional modulation of neural network activity by endocannabinoids.

PubMed

Piet, Richard; Garenne, André; Farrugia, Fanny; Le Masson, Gwendal; Marsicano, Giovanni; Chavis, Pascale; Manzoni, Olivier J

2011-11-16

The endocannabinoid (eCB) system and the cannabinoid CB1 receptor (CB1R) play key roles in the modulation of brain functions. Although actions of eCBs and CB1Rs are well described at the synaptic level, little is known of their modulation of neural activity at the network level. Using microelectrode arrays, we have examined the role of CB1R activation in the modulation of the electrical activity of rat and mice cortical neural networks in vitro. We find that exogenous activation of CB1Rs expressed on glutamatergic neurons decreases the spontaneous activity of cortical neural networks. Moreover, we observe that the net effect of the CB1R antagonist AM251 inversely correlates with the initial level of activity in the network: blocking CB1Rs increases network activity when basal network activity is low, whereas it depresses spontaneous activity when its initial level is high. Our results reveal a complex role of CB1Rs in shaping spontaneous network activity, and suggest that the outcome of endogenous neuromodulation on network function might be state dependent.

Spontaneous facial expressions of emotion of congenitally and noncongenitally blind individuals.

PubMed

Matsumoto, David; Willingham, Bob

2009-01-01

The study of the spontaneous expressions of blind individuals offers a unique opportunity to understand basic processes concerning the emergence and source of facial expressions of emotion. In this study, the authors compared the expressions of congenitally and noncongenitally blind athletes in the 2004 Paralympic Games with each other and with those produced by sighted athletes in the 2004 Olympic Games. The authors also examined how expressions change from 1 context to another. There were no differences between congenitally blind, noncongenitally blind, and sighted athletes, either on the level of individual facial actions or in facial emotion configurations. Blind athletes did produce more overall facial activity, but these were isolated to head and eye movements. The blind athletes' expressions differentiated whether they had won or lost a medal match at 3 different points in time, and there were no cultural differences in expression. These findings provide compelling evidence that the production of spontaneous facial expressions of emotion is not dependent on observational learning but simultaneously demonstrates a learned component to the social management of expressions, even among blind individuals.

Minimally doubled fermions and spontaneous chiral symmetry breaking

NASA Astrophysics Data System (ADS)

Osmanaj (Zeqirllari), Rudina; Hyka (Xhako), Dafina

2018-03-01

Chiral symmetry breaking in massless QCD is a very important feature in the current understanding of low energy physics. Low - lying Dirac modes are suitable to help us understand the spontaneous chiral symmetry breaking, since the formation of a non zero chiral condensate is an effect of their accumulation near zero. The Banks - Casher relation links the spectral density of the Dirac operator to the condensate with an identity that can be read in both directions. In this work we propose a spectral method to achieve a reliable determination of the density of eigenvalues of Dirac operator near zero using the Gauss - Lanczos quadrature. In order to understand better the dynamical chiral symmetry breaking and use the method we propose, we have chosen to work with minimally doubled fermions. These kind of fermions have been proposed as a strictly local discretization of the QCD fermions action, which preserves chiral symmetry at finite cut-off. Being chiral fermions, is easier to work with them and their low - lying Dirac modes and to understand the dynamical spontaneous chiral symmetry breaking.

History of spontaneous miscarriage and the risk of diabetes mellitus among middle-aged and older Chinese women.

PubMed

Liu, Bingqing; Song, Lulu; Li, Hui; Zheng, Xiaoxuan; Yuan, Jing; Liang, Yuan; Wang, Youjie

2018-06-01

Epidemiological studies of the long-term maternal health outcomes of spontaneous miscarriages have been sparse and inconsistent. The objective of our study is to examine the association between spontaneous miscarriages and diabetes among middle-aged and older Chinese women. A total of 19,539 women from the Dongfeng-Tongji cohort study who completed a questionnaire and had medical examinations performed on were included in the analysis. History of spontaneous miscarriage was obtained by self-reporting in the first follow-up questionnaire interview. The presence of diabetes was determined by a fasting plasma glucose level, self-reported physician diagnosis and use of antidiabetic medication. A series of multivariate logistic regression models were used to calculate the odds ratios and 95% CI across spontaneous miscarriage categories (0, 1, 2, ≥ 3) after adjustment for potential confounding factors. The prevalence rate of diabetes was 18.8% among the participants. In the fully adjusted logistic regression model, women who had 1, 2 or ≥ 3 spontaneous miscarriages had 0.86 times (95% CI 0.68, 1.08), 1.30 times (95% CI 0.82, 2.04) and 2.11 times (95% CI 1.08, 4.11) higher risk of diabetes, respectively, compared with women who had no history of spontaneous miscarriage. There is an increased risk of diabetes among women with a history of a higher number of spontaneous miscarriages. History of multiple spontaneous miscarriages should be taken into consideration when assessing the risk of diabetes.

Spontaneous passage of ureteral stones in patients with indwelling ureteral stents.

PubMed

Baumgarten, Lee; Desai, Anuj; Shipman, Scott; Eun, Daniel D; Pontari, Michel A; Mydlo, Jack H; Reese, Adam C

2017-10-01

To determine rates of spontaneous ureteral stone passage in patients with indwelling ureteral stents, and to identify factors associated with the spontaneous passage of stones while a ureteral stent is in place. From our institutional database, we identified patients who underwent ureteroscopic procedures for stone disease between January 1, 2013 and March 1, 2015. We compared the rates of spontaneous stone passage between patients who had previously undergone ureteral stent placement and those who had not. In patients with indwelling stents, multivariate logistic regression was performed to identify factors associated with spontaneous stone passage. A total of 194 patients met inclusion criteria. Spontaneous stone passage rates were similar in the stented (17/119, 14%) and non-stented (15/75, 20%) groups (p = 0.30). In bivariate analysis of stented patients, smaller stone size (p < 0.001) and distal stone location (p = 0.01) were significantly associated with spontaneous stone passage. Multivariate logistic regression analysis of stented patients showed that only small stone size was significantly associated with the likelihood of stone passage (p = 0.01), whereas stent duration, stone location, and stone laterality were not. A small, but clinically significant percentage of ureteral stones pass spontaneously with a ureteral stent in place. Small stone size is associated with an increased likelihood of spontaneous passage in patients with indwelling stents. These findings may help to identify patients who can potentially avoid additional surgical procedures for definitive stone removal after ureteral stent placement.

Light-driven production of ATP catalysed by F0F1-ATP synthase in an artificial photosynthetic membrane

NASA Astrophysics Data System (ADS)

Steinberg-Yfrach, Gali; Rigaud, Jean-Louis; Durantini, Edgardo N.; Moore, Ana L.; Gust, Devens; Moore, Thomas A.

1998-04-01

Energy-transducing membranes of living organisms couple spontaneous to non-spontaneous processes through the intermediacy of protonmotive force (p.m.f.) - an imbalance in electrochemical potential of protons across the membrane. In most organisms, p.m.f. is generated by redox reactions that are either photochemically driven, such as those in photosynthetic reaction centres, or intrinsically spontaneous, such as those of oxidative phosphorylation in mitochondria. Transmembrane proteins (such as the cytochromes and complexes I, III and IV in the electron-transport chain in the inner mitochondrial membrane) couple the redox reactions to proton translocation, thereby conserving a fraction of the redox chemical potential as p.m.f. Many transducer proteins couple p.m.f. to the performance of biochemical work, such as biochemical synthesis and mechanical and transport processes. Recently, an artificial photosynthetic membrane was reported in which a photocyclic process was used to transport protons across a liposomal membrane, resulting in acidification of the liposome's internal volume. If significant p.m.f. is generated in this system, then incorporating an appropriate transducer into the liposomal bilayer should make it possible to drive a non-spontaneous chemical process. Here we report the incorporation of FOF1-ATP synthase into liposomes containing the components of the proton-pumping photocycle. Irradiation of this artificial membrane with visible light results in the uncoupler- and inhibitor-sensitive synthesis of adenosine triphosphate (ATP) against an ATP chemical potential of ~12kcalmol-1, with a quantum yield of more than 7%. This system mimics the process by which photosynthetic bacteria convert light energy into ATP chemical potential.

Taming wild yeast: potential of conventional and nonconventional yeasts in industrial fermentations.

PubMed

Steensels, Jan; Verstrepen, Kevin J

2014-01-01

Yeasts are the main driving force behind several industrial food fermentation processes, including the production of beer, wine, sake, bread, and chocolate. Historically, these processes developed from uncontrolled, spontaneous fermentation reactions that rely on a complex mixture of microbes present in the environment. Because such spontaneous processes are generally inconsistent and inefficient and often lead to the formation of off-flavors, most of today's industrial production utilizes defined starter cultures, often consisting of a specific domesticated strain of Saccharomyces cerevisiae, S. bayanus, or S. pastorianus. Although this practice greatly improved process consistency, efficiency, and overall quality, it also limited the sensorial complexity of the end product. In this review, we discuss how Saccharomyces yeasts were domesticated to become the main workhorse of food fermentations, and we investigate the potential and selection of nonconventional yeasts that are often found in spontaneous fermentations, such as Brettanomyces, Hanseniaspora, and Pichia spp.

Volition and conflict in human medial frontal cortex

PubMed Central

Nachev, Parashkev; Rees, Geraint; Parton, Andrew; Kennard, Christopher; Husain, Masud

2009-01-01

Summary Controversy surrounds the role of human medial frontal cortex in controlling actions[1-5]. Although damage to this area leads to severe difficulties in spontaneously initiating actions[6], the precise mechanisms underlying such ‘volitional’ deficits remain to be established. Previous studies have implicated the medial frontal cortex in conflict monitoring[7-10] and the control of voluntary action[11, 12], suggesting that these key processes are functionally related or share neural substrates. Here we combine a novel behavioural paradigm with functional imaging of the oculomotor system to reveal for the first time a functional subdivision of the pre-supplementary motor area (pre-SMA) into anatomically distinct areas responding exclusively to volition or to conflict. We also demonstrate that activity in the supplementary eye field (SEF) distinguishes between success and failure in changing voluntary action plans during conflict, suggesting a role for the SEF in implementing the resolution of conflicting actions. We propose a functional architecture of human medial frontal cortex that incorporates the generation of action plans and the resolution of conflict. PMID:15668167

Action anticipation in human infants reveals assumptions about anteroposterior body-structure and action.

PubMed

Hernik, Mikolaj; Fearon, Pasco; Csibra, Gergely

2014-04-22

Animal actions are almost universally constrained by the bilateral body-plan. For example, the direction of travel tends to be constrained by the orientation of the animal's anteroposterior axis. Hence, an animal's behaviour can reliably guide the identification of its front and back, and its orientation can reliably guide action prediction. We examine the hypothesis that the evolutionarily ancient relation between anteroposterior body-structure and behaviour guides our cognitive processing of agents and their actions. In a series of studies, we demonstrate that, after limited exposure, human infants as young as six months of age spontaneously encode a novel agent as having a certain axial direction with respect to its actions and rely on it when anticipating the agent's further behaviour. We found that such encoding is restricted to objects exhibiting cues of agency and does not depend on generalization from features of familiar animals. Our research offers a new tool for investigating the perception of animate agency and supports the proposal that the underlying cognitive mechanisms have been shaped by basic biological adaptations in humans.

Spontaneous thrombosis of the main draining vein revealing an unruptured brain arteriovenous malformation

PubMed Central

Cao, Catherine; Sourour, Nader; Reina, Vincent; Nouet, Aurélien; Di Maria, Federico; Chiras, Jacques; Cornu, Philippe

2015-01-01

Haemorrhage is the most frequent revealing condition of brain arteriovenous malformations (bAVMs). We report a rare case of unruptured parietal bAVM revealed by spontaneous thrombosis of the main draining vein, responsible for a focal neurological deficit. The bAVM was embolized in emergency conditions; complete regression of the neurological symptoms was observed within five days after the embolization. Potential mechanisms of such spontaneous thrombosis of the bAVM’s main drainage pathway as well as an exhaustive review of the literature concerning this rare revealing condition are presented and discussed. PMID:25964440

Ca2+-regulated-cAMP/PKA signaling in cardiac pacemaker cells links ATP supply to demand.

PubMed

Yaniv, Yael; Juhaszova, Magdalena; Lyashkov, Alexey E; Spurgeon, Harold A; Sollott, Steven J; Lakatta, Edward G

2011-11-01

In sinoatrial node cells (SANC), Ca(2+) activates adenylate cyclase (AC) to generate a high basal level of cAMP-mediated/protein kinase A (PKA)-dependent phosphorylation of Ca(2+) cycling proteins. These result in spontaneous sarcoplasmic-reticulum (SR) generated rhythmic Ca(2+) oscillations during diastolic depolarization, that not only trigger the surface membrane to generate rhythmic action potentials (APs), but, in a feed-forward manner, also activate AC/PKA signaling. ATP is consumed to pump Ca(2+) to the SR, to produce cAMP, to support contraction and to maintain cell ionic homeostasis. Since feedback mechanisms link ATP-demand to ATP production, we hypothesized that (1) both basal ATP supply and demand in SANC would be Ca(2+)-cAMP/PKA dependent; and (2) due to its feed-forward nature, a decrease in flux through the Ca(2+)-cAMP/PKA signaling axis will reduce the basal ATP production rate. O(2) consumption in spontaneous beating SANC was comparable to ventricular myocytes (VM) stimulated at 3 Hz. Graded reduction of basal Ca(2+)-cAMP/PKA signaling to reduce ATP demand in rabbit SANC produced graded ATP depletion (r(2)=0.96), and reduced O(2) consumption and flavoprotein fluorescence. Neither inhibition of glycolysis, selectively blocking contraction nor specific inhibition of mitochondrial Ca(2+) flux reduced the ATP level. Feed-forward basal Ca(2+)-cAMP/PKA signaling both consumes ATP to drive spontaneous APs in SANC and is tightly linked to mitochondrial ATP production. Interfering with Ca(2+)-cAMP/PKA signaling not only slows the firing rate and reduces ATP consumption, but also appears to reduce ATP production so that ATP levels fall. This distinctly differs from VM, which lack this feed-forward basal cAMP/PKA signaling, and in which ATP level remains constant when the demand changes. Published by Elsevier Ltd.

Intrinsic spontaneous activity and subthreshold oscillations in neurones of the rat dorsal column nuclei in culture

PubMed Central

Reboreda, Antonio; Sánchez, Estela; Romero, Marcos; Lamas, J Antonio

2003-01-01

The basis of rhythmic activity observed at the dorsal column nuclei (DCN) is still open to debate. This study has investigated the electrophysiological properties of isolated DCN neurones deprived of any synaptic influence, using the perforated-patch technique. About half of the DCN neurones (64/130) were spontaneously active. More than half of the spontaneous neurones (36/64) showed a low threshold membrane oscillation (LTO) with a mean frequency of 11.4 Hz (range: 4.3–22.1 Hz, n = 20; I = 0). Cells showing LTOs also invariably showed a rhythmic 1.2 Hz clustering activity (groups of 2–5 action potentials separated by silent LTO periods). Also, more than one-third of the silent neurones presented clustering activity, always accompanied by LTOs, when slightly depolarised. The frequency of LTOs was voltage dependent and could be abolished by TTX (0.5 μM) and riluzole (30 μM), suggesting the participation of a sodium current. LTOs were also abolished by TEA (15 mM), which transformed clustering into tonic activity. In voltage clamp, most DCN neurones (85 %) showed a TTX-/riluzole-sensitive persistent sodium current (INa,p), which activated at about -60 mV and had a half-maximum activation at −49.8 mV. An M-like, non-inactivating outward current was present in 95 % of DCN neurones, and TEA (15 mM) inhibited this current by 73.7 %. The non-inactivating outward current was also inhibited by barium (1 mM) and linopirdine (10 μM), which suggests its M-like nature; both drugs failed to block the LTOs, but induced a reduction in their frequency by 56 and 20 %, respectively. These results demonstrate for the first time that DCN neurones have a complex and intrinsically driven clustering discharge pattern, accompanied by subthreshold membrane oscillations. Subthreshold oscillations rely on the interplay of a persistent sodium current and a non-inactivating TEA-sensitive outward current. PMID:12844503

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aschengrau, A.; Zierler, S.; Cohen, A.

To investigate the relationship between community drinking water quality and spontaneous abortion, we compared trace element levels in the drinking water of 286 women having a spontaneous abortion through 27 wk gestation with that of 1,391 women having live births. Trace element levels were gathered from analyses of public tap water supplies from the communities where the women resided during pregnancy. After adjustment for potential confounders, an increase in the frequency of spontaneous abortion was associated with detectable levels of mercury; high levels of arsenic, potassium, and silica; moderately hard water, and surface water. In contrast, a decrease in themore » frequency of spontaneous abortion was associated with high levels of alkalinity and sulfate, and any detectable level of nitrate. These results require further corroboration because there is a paucity of data investigating this issue.« less

Tonic suppression of spontaneous baroreceptor reflex by endogenous angiotensins via AT(2) subtype receptors at nucleus reticularis ventrolateralis in the rat.

PubMed

Lin, K; Chan, S H; Chan, J Y

2001-04-01

We evaluated the role of endogenous angiotensins at the rostral nucleus reticularis ventrolateralis (NRVL) in the modulation of spontaneous baroreceptor reflex (BRR) response and the subtype of angiotensin receptors involved using rats anesthetized and maintained with pentobarbital sodium. Bilateral microinjection of angiotensin II (ANG II) or its active metabolite angiotensin III (ANG III) (5, 10, or 20 pmol) into the NRVL significantly suppressed the spontaneous BRR response, as represented by the magnitude of transfer function between systemic arterial pressure and heart rate signals. The inhibitory effect of ANG III (20 pmol) was discernibly reversed by coadministration with its peptide antagonist, [Ile(7)]ANG III (1.6 nmol), or the nonpeptide AT(2) receptor antagonist, PD-123319 (1.6 nmol), but not by the nonpeptide AT(1) receptor antagonist, losartan (1.6 nmol). On the other hand, the peptide antagonist, [Sar(1), Ile(8)]ANG II (1.6 nmol) or both non-peptide antagonists appreciably reversed the suppressive action of ANG II (20 pmol). Whereas losartan produced minimal effect, blocking the endogenous activity of the angiotensins by microinjection into the bilateral NRVL of PD-123319, [Sar(1), Ile(8)]ANG II or [Ile(7)]ANG III elicited significant enhancement of the spontaneous BRR response. We conclude that under physiologic conditions both endogenous ANG II and ANG III may exert a tonic inhibitory modulation on the spontaneous BRR response by acting selectively on the AT(2) subtype receptors at the NRVL. Copyright 2001 Wiley-Liss, Inc.

Substance-P antagonists: effect on spontaneous and drug-induced locomotor activity in the rat.

PubMed

Elliott, P J; Iversen, S D

1987-05-01

The substance P (SP) antagonists (D-Pro4, D-Trp7,9, Leu11) SP(4-11), (D-Pro4, D-Trp7,9, Phe11)SP(4-11) and (D-Pro4, D-Trp7,9,10, Leu11) SP (4-11) were infused into the lateral ventricles (i.c.v.) and their effects on spontaneous and drug-induced locomotor activity were investigated. The drug DiMeC7, the stable substance P agonist, was used to stimulate locomotor activity because of its prolonged action. Only (D-Pro4, D-Trp7,9,10) SP (4-11) was found to attenuate the drug-induced increases in motor activity, indicating that it is a substance P antagonist with activity in the CNS.

Accelerating universe with time variation of G and Λ

NASA Astrophysics Data System (ADS)

Darabi, F.

2012-03-01

We study a gravitational model in which scale transformations play the key role in obtaining dynamical G and Λ. We take a non-scale invariant gravitational action with a cosmological constant and a gravitational coupling constant. Then, by a scale transformation, through a dilaton field, we obtain a new action containing cosmological and gravitational coupling terms which are dynamically dependent on the dilaton field with Higgs type potential. The vacuum expectation value of this dilaton field, through spontaneous symmetry breaking on the basis of anthropic principle, determines the time variations of G and Λ. The relevance of these time variations to the current acceleration of the universe, coincidence problem, Mach's cosmological coincidence and those problems of standard cosmology addressed by inflationary models, are discussed. The current acceleration of the universe is shown to be a result of phase transition from radiation toward matter dominated eras. No real coincidence problem between matter and vacuum energy densities exists in this model and this apparent coincidence together with Mach's cosmological coincidence are shown to be simple consequences of a new kind of scale factor dependence of the energy momentum density as ρ˜ a -4. This model also provides the possibility for a super fast expansion of the scale factor at very early universe by introducing exotic type matter like cosmic strings.