The Experts below are selected from a list of 117 Experts worldwide ranked by ideXlab platform
Logan J. Voss - One of the best experts on this subject based on the ideXlab platform.
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quantitative investigation into methods for evaluating Neocortical Slice viability
BMC Neuroscience, 2013Co-Authors: Logan J. Voss, Claudia Van Kan, J W SleighAbstract:In cortical and hippocampal brain Slice experiments, the viability of processed tissue is usually judged by the amplitude of extracellularly-recorded seizure-like event (SLE) activity. Surprisingly, the suitability of this approach for evaluating Slice quality has not been objectively studied. Furthermore, a method for gauging the viability of quiescent tissue, in which SLE activity is intentionally suppressed, has not been documented. In this study we undertook to address both of these matters using the zero-magnesium SLE model in Neocortical Slices. Using zero-magnesium SLE activity as the output parameter, we investigated: 1) changes in the pattern (amplitude, frequency and length) of SLE activity as Slice health either deteriorated; or was compromised by altering the preparation methodology and; 2) in quiescent tissue, whether the triggering of high frequency field activity following electrode insertion predicted subsequent development of SLE activity — and hence Slice viability. SLE amplitude was the single most important variable correlating with Slice viability, with a value less than 50 μV indicative of tissue unlikely to be able to sustain population activity for more than 30–60 minutes. In quiescent Slices, an increase in high frequency field activity immediately after electrode insertion predicted the development of SLE activity in 100% of cases. Furthermore, the magnitude of the increase in spectral power correlated with the amplitude of succeeding SLE activity (R2 40.9%, p < 0.0001). In conclusion, the findings confirm that the amplitude of population activity is a suitable field potential parameter for judging brain Slice viability — and can be applied independent of the mechanism of tissue activation.
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Quantification of Neocortical Slice Diffusion Characteristics Using Pharmacokinetic and Pharmacodynamic Modelling
ISRN neuroscience, 2013Co-Authors: Logan J. Voss, Claudia Van Kan, James W. SleighAbstract:Pharmacological brain Slice experiments are complicated by the need to ensure adequate drug delivery deep into the healthy layers of the tissue. Because tissue Slices have no blood supply, this is achieved solely by passive drug diffusion. The aim of this study was to determine whether pharmacokinetic/pharmacodynamic (PKPD) modeling could be adapted to estimate drug diffusion times in Neocortical brain Slices. No-magnesium seizure-like event (SLE) activity was generated in 41 Slices (400 μm). Two anesthetic agents, etomidate (24 μM, ) and thiopental (250 μM, ), and magnesium ions () were delivered to effect reversible reductions in SLE frequency. Concentration-effect hysteresis loops were collapsed using a first order rate constant model and equilibrium half-lives () derived. The values obtained were consistent with expectations. The median (range) of 83.1 (19.4–330.1) min for etomidate is in keeping with its known slow diffusion into brain Slice tissue. Values for etomidate and thiopental (111.8 (27.8–198.0) min) were similar, while magnesium had a significantly faster equilibration rate ( of 26.1 (8.6–77.0) min) compared to the anesthetics, as expected for a simple ion. In conclusion, PKPD modeling is a simple and practical method that can be applied to brain Slice experiments for investigating drug diffusion characteristics.
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Investigation into the effect of the general anaesthetic etomidate on local neuronal synchrony in the mouse Neocortical Slice
Brain research, 2013Co-Authors: Logan J. Voss, Cecilia Hansson Baas, Linnea Hansson, James W. SleighAbstract:Abstract How general anaesthetic drugs cause unconsciousness is a topic of ongoing clinical and scientific interest. It is becoming increasingly apparent that they disrupt cortical information processing, but the effects appear to depend on the spatial scale under investigation. In this study we investigated whether the intravenous anaesthetic etomidate synchronises neuronal activity on a sub-millimetre scale in mouse Neocortical Slices. In Slices generating no-magnesium seizure-like event (SLE) field activity, we analysed the morphology of field potential activity recorded with 50 µm extracellular electrodes. The analysis was based on the understanding that the amplitude and sheerness of field potential oscillations correlates with the synchrony of the underlying neural activity. When recorded from the region of the Slice initiating SLE activity, etomidate consistently increased both population event amplitude (median(range) 85(24–350) to 101(30–427) µV) and slope 16.6(1.5–106.2) to 20.2(1.7–111.1) µV/ms (p=0.016 and p=0.0013, respectively). The results are consistent with an increase in neuronal synchrony within the receptive field of the recording electrode, estimated to be a circle diameter of 300 µm. In conclusion, the Neocortical Slice preparation supports in vivo data showing that general anaesthetics increase neuronal synchrony on a local scale and provides an ideal model for investigating underlying mechanisms.
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Research Article Quantification of Neocortical Slice Diffusion Characteristics
2013Co-Authors: Isrn Neuroscience, Logan J. Voss, Claudia Van Kan, Using Pharmacokinetic, Pharmacodynamic Modelling, James W. SleighAbstract:which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Pharmacological brain Slice experiments are complicated by the need to ensure adequate drug delivery deep into the healthy layers of the tissue. Because tissue Slices have no blood supply, this is achieved solely by passive drug diffusion. The aim of this study was to determine whether pharmacokinetic/pharmacodynamic (PKPD) modeling could be adapted to estimate drug diffusion times in Neocortical brain Slices. No-magnesium seizure-like event (SLE) activity was generated in 41 Slices (40
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Investigation into the effect of the general anaesthetics etomidate and ketamine on long-range coupling of population activity in the mouse Neocortical Slice.
European Journal of Pharmacology, 2012Co-Authors: Logan J. Voss, Cecilia Hansson Baas, Linnea Hansson, D Alistair Steyn-ross, Moira Steyn-ross, James W. SleighAbstract:Abstract General anaesthetics have been hypothesised to ablate consciousness by decoupling intracortical neural connectivity. We explored this by investigating the effect of etomidate and ketamine on coupling of neural population activity using the low magnesium Neocortical Slice model. Four extracellular electrodes (50 μm) were positioned in mouse Neocortical Slices (400 μm thick) with varying separation. The effect of etomidate (24 μM) and ketamine (16 μM) on the timing of population activity recorded between channels was analysed. No decoupling was observed at the closest electrode separation of 0.2 mm. At 4 mm separation, decoupling was observed in 50% and 42% of Slices during etomidate and ketamine delivery, respectively ( P P =0.002, compared to 0.2 mm separation). A lower rate of decoupling was observed with 1 mm separation (21% and 8%, respectively, P
Erwin-josef Speckmann - One of the best experts on this subject based on the ideXlab platform.
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effects of retigabine on rhythmic synchronous activity of human Neocortical Slices
Epilepsy Research, 2001Co-Authors: H Straub, Jorgmichael Hohling, Ingrid Tuxhorn, A Ebner, Rudiger Kohling, H Pannek, Peter Wolf, Chris Rundfeldt, Erwin-josef SpeckmannAbstract:Abstract The antiepileptic effects of the novel antiepileptic drug retigabine (D-23129) [N-(2-amino-4-(4-flurobenzylamino)phenyl) carbamid acid ethyl ester] were tested in Neocortical Slice preparations (n=23) from 17 patients (age, 3–42 years) who underwent surgery for the treatment of intractable epilepsy. Epileptiform events consisted of spontaneously occurring rhythmic sharp waves, as well as of epileptiform field potentials (EFP) elicited by superfusion with Mg2+-free solution without or with addition of 10 μmol/l bicuculline. (1) Spontaneous rhythmic sharp waves (n=6), with retigabine application, the repetition rate was decreased down to 12–47% of initial value (10 μmol/l, n=3) after 180 min or suppressed completely within 12 min (50 μmol/l, n=3). (2) Low Mg2+ EFP (n=9), with retigabine application, the repetition rate was decreased down to 50 and 65% of initial value (10 μmol/l; n=2) after 180 min or suppressed completely after 9–55 min (10, 50 and 100 μmol/l; n=2 in each case). In one Slice only a transient reduction of the repetition rate was seen with 10 μmol/l retigabine. (3) Low Mg2+ EFP with addition of bicuculline (n=8), with retigabine application, the repetition rate was decreased down to 12–55% of initial value (10 μmol/l; n=4) after 180 min or suppressed completely after 6–30 min (50 and 100 μmol/l; n=2 in each case). The depressive effect of retigabine was reversible in all but one Slice. The results show a clear antiepileptic effect of retigabine in human Neocortical Slices on spontaneously occurring rhythmic sharp waves and different types of induced seizure activity.
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Influence of the organic calcium antagonist verapamil on N-methyl-d-aspartate (NMDA) induced cortical field potentials (Neocortical Slice, guinea pig)
Neuroscience Letters, 1993Co-Authors: Andreas Lücke, Erwin-josef SpeckmannAbstract:In the present experiments it was tested whether the organic calcium antagonist verapamil has an influence on N-methyl-d-aspartate (NMDA) induced cortical field potentials (CFP) in Neocortical Slices of guinea pigs. NMDA (1 ??mol/l) was applied via a micropipette by pressure pulses. Verapamil (60 ??mol/l) was administered by bath application or ejected locally (100 ??mol/l) and simultaneously with NMDA. Neither the systemic administration nor the local application of verapamil had an influence on NMDA induced CFP. It is concluded that the antiepileptic effect of verapamil is not mediated via the NMDA receptor. ?? 1993.
Ulrich Kuhnt - One of the best experts on this subject based on the ideXlab platform.
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Epileptiform activity in the guinea-pig Neocortical Slice spreads preferentially along supragranular layers--recordings with voltage-sensitive dyes.
The European journal of neuroscience, 1995Co-Authors: Birgit Albowitz, Ulrich KuhntAbstract:The spread of epileptiform activity was monitored in guinea-pig Neocortical Slices by the use of a voltagesensitive dye (RH795) and a fast optical recording technique. Epileptiform activity induced by bicuculline methiodide (10-20 FM) and single-pulse stimulation spread from the stimulation site in layer I or in the white matter across most of the Slice. Different lesions were made in the Slice in order to specify the neuronal connections used for spread in the horizontal direction. In the Slice, intracortical connections are necessary for the spread of epileptiform activity, as shown by vertical cuts through all cortical layers but sparing the white matter. Horizontal connections were interrupted by cuts parallel to the axis of pyramidal neurons through either supragranular or infragranular layers. Vertical connections were interrupted by cuts perpendicular to the axis of pyramidal neurons separating supragranular and infragranular layers. Spread of epileptiform activity in the horizontal direction was not hindered by horizontal cuts. Vertical cuts through infragranular layers also did not hinder the spread of epileptiform activity. In contrast, vertical cuts through supragranular layers either abolished completely (nine Slices) or delayed significantly (ten Slices) the spread of epileptiform activity. The mean delay at the supragranular lesion was 44 ms in layer Ill and 30 ms in layer V; at the infragranular lesion the mean delay was 2 ms in layer Ill and 6 ms in layer V. Also, with horizontal cuts, in three out of five Slices the velocity of spread was significantly lower in infragranular as compared to supragranular layers. It is concluded that both supra- and infragranular layers if isolated possess the ability to initiate and propagate epileptiform activity independently. However, in the intact Slice the influence of the supragranular networks on initiation and propagation of epileptiform activity appears to dominate.
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Spread of epileptiform potentials in the Neocortical Slice: recordings with voltage-sensitive dyes.
Brain research, 1993Co-Authors: Birgit Albowitz, Ulrich KuhntAbstract:Abstract The spread of epileptiform potentials in guinea pig Neocortical Slices was investigated by use of voltage sensitive dyes and a fast optical recording technique. Epileptiform activity was induced in a perfusion medium containing 10–20 μM bicuculline-methiodide and by single pulse stimulation of layer I or the white matter. The location of minimal and maximal amplitudes, the shape of the potentials at specific sites and the velocity of spread were independent from the specific stimulation site. The expression of epileptiform activity appeared to depend on specific, possibly geometrical, properties of the tissue.
James W. Sleigh - One of the best experts on this subject based on the ideXlab platform.
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Quantification of Neocortical Slice Diffusion Characteristics Using Pharmacokinetic and Pharmacodynamic Modelling
ISRN neuroscience, 2013Co-Authors: Logan J. Voss, Claudia Van Kan, James W. SleighAbstract:Pharmacological brain Slice experiments are complicated by the need to ensure adequate drug delivery deep into the healthy layers of the tissue. Because tissue Slices have no blood supply, this is achieved solely by passive drug diffusion. The aim of this study was to determine whether pharmacokinetic/pharmacodynamic (PKPD) modeling could be adapted to estimate drug diffusion times in Neocortical brain Slices. No-magnesium seizure-like event (SLE) activity was generated in 41 Slices (400 μm). Two anesthetic agents, etomidate (24 μM, ) and thiopental (250 μM, ), and magnesium ions () were delivered to effect reversible reductions in SLE frequency. Concentration-effect hysteresis loops were collapsed using a first order rate constant model and equilibrium half-lives () derived. The values obtained were consistent with expectations. The median (range) of 83.1 (19.4–330.1) min for etomidate is in keeping with its known slow diffusion into brain Slice tissue. Values for etomidate and thiopental (111.8 (27.8–198.0) min) were similar, while magnesium had a significantly faster equilibration rate ( of 26.1 (8.6–77.0) min) compared to the anesthetics, as expected for a simple ion. In conclusion, PKPD modeling is a simple and practical method that can be applied to brain Slice experiments for investigating drug diffusion characteristics.
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Investigation into the effect of the general anaesthetic etomidate on local neuronal synchrony in the mouse Neocortical Slice
Brain research, 2013Co-Authors: Logan J. Voss, Cecilia Hansson Baas, Linnea Hansson, James W. SleighAbstract:Abstract How general anaesthetic drugs cause unconsciousness is a topic of ongoing clinical and scientific interest. It is becoming increasingly apparent that they disrupt cortical information processing, but the effects appear to depend on the spatial scale under investigation. In this study we investigated whether the intravenous anaesthetic etomidate synchronises neuronal activity on a sub-millimetre scale in mouse Neocortical Slices. In Slices generating no-magnesium seizure-like event (SLE) field activity, we analysed the morphology of field potential activity recorded with 50 µm extracellular electrodes. The analysis was based on the understanding that the amplitude and sheerness of field potential oscillations correlates with the synchrony of the underlying neural activity. When recorded from the region of the Slice initiating SLE activity, etomidate consistently increased both population event amplitude (median(range) 85(24–350) to 101(30–427) µV) and slope 16.6(1.5–106.2) to 20.2(1.7–111.1) µV/ms (p=0.016 and p=0.0013, respectively). The results are consistent with an increase in neuronal synchrony within the receptive field of the recording electrode, estimated to be a circle diameter of 300 µm. In conclusion, the Neocortical Slice preparation supports in vivo data showing that general anaesthetics increase neuronal synchrony on a local scale and provides an ideal model for investigating underlying mechanisms.
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Research Article Quantification of Neocortical Slice Diffusion Characteristics
2013Co-Authors: Isrn Neuroscience, Logan J. Voss, Claudia Van Kan, Using Pharmacokinetic, Pharmacodynamic Modelling, James W. SleighAbstract:which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Pharmacological brain Slice experiments are complicated by the need to ensure adequate drug delivery deep into the healthy layers of the tissue. Because tissue Slices have no blood supply, this is achieved solely by passive drug diffusion. The aim of this study was to determine whether pharmacokinetic/pharmacodynamic (PKPD) modeling could be adapted to estimate drug diffusion times in Neocortical brain Slices. No-magnesium seizure-like event (SLE) activity was generated in 41 Slices (40
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Investigation into the effect of the general anaesthetics etomidate and ketamine on long-range coupling of population activity in the mouse Neocortical Slice.
European Journal of Pharmacology, 2012Co-Authors: Logan J. Voss, Cecilia Hansson Baas, Linnea Hansson, D Alistair Steyn-ross, Moira Steyn-ross, James W. SleighAbstract:Abstract General anaesthetics have been hypothesised to ablate consciousness by decoupling intracortical neural connectivity. We explored this by investigating the effect of etomidate and ketamine on coupling of neural population activity using the low magnesium Neocortical Slice model. Four extracellular electrodes (50 μm) were positioned in mouse Neocortical Slices (400 μm thick) with varying separation. The effect of etomidate (24 μM) and ketamine (16 μM) on the timing of population activity recorded between channels was analysed. No decoupling was observed at the closest electrode separation of 0.2 mm. At 4 mm separation, decoupling was observed in 50% and 42% of Slices during etomidate and ketamine delivery, respectively ( P P =0.002, compared to 0.2 mm separation). A lower rate of decoupling was observed with 1 mm separation (21% and 8%, respectively, P
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Stability of brain Neocortical Slice seizure-like activity during low-magnesium exposure: Measurement and effect of artificial cerebrospinal fluid temperature.
Journal of neuroscience methods, 2010Co-Authors: Logan J. Voss, James W. SleighAbstract:Abstract Low-magnesium perfusion is an established method for inducing seizure-like activity in Neocortical Slices and is widely utilized as a model of human epilepsy. However, many contentious issues remain around optimizing in vitro cortical Slice experimental protocols. In this study we investigated the stability of low-magnesium seizure-like event (SLE) activity at different perfusion temperatures; with an aim towards determining whether time-dependent effects in this preparation could be attributed to a reduction in tissue viability. The results showed that SLE characteristics changed significantly and consistently over a 3 h recording period, independent of artificial cerebrospinal fluid temperature; there was a median increase in event frequency of 61% (p
J W Sleigh - One of the best experts on this subject based on the ideXlab platform.
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quantitative investigation into methods for evaluating Neocortical Slice viability
BMC Neuroscience, 2013Co-Authors: Logan J. Voss, Claudia Van Kan, J W SleighAbstract:In cortical and hippocampal brain Slice experiments, the viability of processed tissue is usually judged by the amplitude of extracellularly-recorded seizure-like event (SLE) activity. Surprisingly, the suitability of this approach for evaluating Slice quality has not been objectively studied. Furthermore, a method for gauging the viability of quiescent tissue, in which SLE activity is intentionally suppressed, has not been documented. In this study we undertook to address both of these matters using the zero-magnesium SLE model in Neocortical Slices. Using zero-magnesium SLE activity as the output parameter, we investigated: 1) changes in the pattern (amplitude, frequency and length) of SLE activity as Slice health either deteriorated; or was compromised by altering the preparation methodology and; 2) in quiescent tissue, whether the triggering of high frequency field activity following electrode insertion predicted subsequent development of SLE activity — and hence Slice viability. SLE amplitude was the single most important variable correlating with Slice viability, with a value less than 50 μV indicative of tissue unlikely to be able to sustain population activity for more than 30–60 minutes. In quiescent Slices, an increase in high frequency field activity immediately after electrode insertion predicted the development of SLE activity in 100% of cases. Furthermore, the magnitude of the increase in spectral power correlated with the amplitude of succeeding SLE activity (R2 40.9%, p < 0.0001). In conclusion, the findings confirm that the amplitude of population activity is a suitable field potential parameter for judging brain Slice viability — and can be applied independent of the mechanism of tissue activation.
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testing Neocortical Slice viability in non perfused no magnesium artificial cerebrospinal fluid solutions
Journal of Neuroscience Methods, 2012Co-Authors: Logan J. Voss, Shwetha A George, J W SleighAbstract:Abstract The acute in vitro brain Slice model is a widely used neurophysiological research tool. When applying this method, most researchers continuously perfuse Slices with carbogenated artificial cerebrospinal fluid (ACSF) to maintain pH balance and tissue oxygen delivery. Common wisdom suggests that static recordings are incompatible with submerged bath methodology because of deficiency in tissue oxygen supply. However, to our knowledge this has not been tested. In this study, we wanted to determine whether Neocortical mouse Slice viability could be maintained in the medium term (up to 2 h) in a shallow, submerged recording bath under non-perfused, static conditions. Seizure-like events (SLEs) were generated in the Slices utilizing no-magnesium ACSF and recorded for 2 h under three conditions: (1) perfused ACSF condition ( n = 8), where Slices were perfused continuously with carbogenated no-magnesium ACSF; (2) static ACSF condition ( n = 12), where Slices were recorded in pre-carbogenated, but non-perfused (static) no-magnesium ACSF; and (3) static HEPES ACSF condition ( n = 12), where Slices were recorded in non-perfused (static) no-magnesium ACSF with no pre-carbogenation but buffered with HEPES. SLE activity was stable for 2 h across all three conditions. There was no statistically significant difference in SLE frequency, amplitude or length between static and perfused conditions. SLE frequency and amplitude were generally lower in the static HEPES buffer condition. The data indicate that robust and stable Neocortical SLE activity can be generated for at least 2 h in a submersion bath without ACSF perfusion if pH is adequately controlled.
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investigating paradoxical hysteresis effects in the mouse Neocortical Slice model
European Journal of Pharmacology, 2012Co-Authors: Logan J. Voss, Magdalena Brock, Cecilia Carlsson, Alistair D Steynross, Moira L Steynross, J W SleighAbstract:Clinically, anesthetic drugs show hysteresis in the plasma drug concentrations at induction versus emergence from anesthesia induced unconsciousness. This is assumed to be the result of pharmacokinetic lag between the plasma and brain effect-site and vice versa. However, recent mathematical and experimental studies demonstrate that anesthetic hysteresis might be due in part to lag in the brain physiology, independent of drug transport delay - so-called "neural inertia". The aim of this study was to investigate neural inertia in the reduced Neocortical mouse Slice model. Seizure-like event (SLE) activity was generated by exposing cortical Slices to no-magnesium artificial cerebrospinal fluid (aCSF). Concentration-effect loops were generated by manipulating SLE frequency, using the general anesthetic drug etomidate and by altering the aCSF magnesium concentration. The etomidate (24 μM) concentration-effect relationship showed a clear hysteresis, consistent with the slow diffusion of etomidate into Slice tissue. Manipulation of tissue excitability, using either carbachol (50 μM) or elevated potassium (5mM vs 2.5mM) did not significantly alter the size of etomidate hysteresis loops. Hysteresis in the magnesium concentration-effect relationship was evident, but only when the starting condition was magnesium-containing "normal" aCSF. The in vitro cortical Slice manifests pathway-dependent "neural inertia" and may be a valuable model for future investigations into the mechanisms of neural inertia in the cerebral cortex.
