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J L Perez Velazquez

Publications and source records attributed to J L Perez Velazquez.

At least 19 recordsLinked to original sources
PubMed2005

EEG nonstationarity during intracranially recorded seizures: statistical and dynamical analysis.

OBJECTIVE: The investigation of nonstationarity in complex, multivariable signals, such as electroencephalographic (EEG) recordings, requires the application of different and novel approaches to analysis. In this study, we have divided the EEG recordings during epileptic seizures into sequential stages using spectral and statistical analysis, and have as well reconstructed discrete-time models (maps) that reflect dynamical (deterministic) properties of the EEG voltage time series. METHODS: Intracranial human EEG recordings with epileptic seizures from three different subjects with medically intractable temporal lobe epilepsy were studied. The methods of statistical (power spectra, wavelet spectra, and one-dimensional probability distribution functions) and dynamical (comparison of dynamical models) nonstationarity analysis were applied. RESULTS: Dynamical nonstationarity analysis revealed more detailed inner structure within the seizures than the statistical analysis. Three or four stages with different dynamics are typically present within seizures. The difference between interictal activity and seizure events was also more evident through dynamical analysis. CONCLUSIONS: Nonstationarity analysis can reveal temporal structure within an epileptic seizure, which could further understanding of how seizures evolve. The method could also be used for identification of seizure onset. SIGNIFICANCE: Our approach reveals new information about the temporal structure of seizures, which is inaccessible using conventional methods.

Electroencephalography↗
PubMed2005

Estimation of coupling between oscillators from short time series via phase dynamics modeling: limitations and application to EEG data.

We demonstrate in numerical experiments that estimators of strength and directionality of coupling between oscillators based on modeling of their phase dynamics [D. A. Smirnov and B. P. Bezruchko, Phys. Rev. E 68, 046209 (2003)] are widely applicable. Namely, although the expressions for the estimators and their confidence bands are derived for linear uncoupled oscillators under the influence of independent sources of Gaussian white noise, they turn out to allow reliable characterization of coupling from relatively short time series for different properties of noise, significant phase nonlinearity of the oscillators, and nonvanishing coupling between them. We apply the estimators to analyze a two-channel human intracranial epileptic electroencephalogram (EEG) recording with the purpose of epileptic focus localization.

Artifacts↗
PubMed2001

Dynamics of intracellular calcium and free radical production during ischemia in pyramidal neurons.

Biochemical cascades initiated by oxidative stress and excitotoxic intracellular calcium rises are thought to converge on mitochondrial dysfunction. We investigated the contribution of mitochondrial dysfunction to free radical (FR) overproduction in rat CA1 pyramidal neurons of organotypic slices subjected to a hypoxic-hypoglycemic insult. Ischemia-induced FR generation was decreased by the mitochondrial complex I blocker, rotenone, indicating that mitochondria are the principal source of ischemic FR production. Measurements of mitochondrial calcium with the mitochondrial calcium probe dihydroRhod-2, revealed that FR production during and after the anoxic episode correlates with the accumulation of mitochondrial calcium. However, the mitochondrial calcium uptake inhibitor Ru360 did not prevent FR generation during ischemia and attenuated it to some degree during reoxygenation. On the other hand, the mitochondrial permeability transition blocker cyclosporinA (CsA) completely arrested both ischemic FR generation and mitochondrial calcium overload, and prevented deterioration of neuronal intrinsic membrane properties. CsA had no effect on the accumulation of intracellular calcium during ischemia-reperfusion. Nicotinamide, a blocker of NAD+ hydrolysis, reproduced the CsA effects on FR generation, mitochondrial calcium accumulation and cytoplasmic calcium increases. These observations suggest that a major determinant of ischemic FR generation in pyramidal neurons is the uncoupling of the mitochondrial respiratory chain, which may be associated with the mitochondrial permeability transition.

Aniline Compounds↗
PubMed2001

Artificial electrotonic coupling affects neuronal firing patterns depending upon cellular characteristics.

While there have been numerous theoretical studies indicating that electrotonic coupling via gap junctions interacts with the intrinsic characteristics of the coupled neurons to modify their electrical behaviour, little experimental evidence has been provided in coupled mammalian neurons. Using an artificial electrotonic junction, two distant uncoupled neurons were coupled through the computer, and the coupling conductance was varied. Tonically firing CA1 hippocampal pyramidal neurons reduced their spike firing frequency when coupled to thalamic or pyramidal cells, showing that the electrical coupling can be considered as a low-pass filter. The strength of coupling needed to entrain spike bursts of pyramidal neurons was considerably lower than the coupling needed to synchronize two neurons with different cellular characteristics (thalamic and pyramidal cells). Coupling promoted burst firing in a non-bursting cell if it was coupled to a spontaneously bursting neuron. These results support modelling studies that indicate a role for gap-junctional coupling in the synchronization of neuronal firing and the expression of low-frequency bursting.

Action Potentials↗
PubMed2000

The role of gap junctions in seizures.

Electrotonic synaptic communication between neurons via gap junctions (gjs) is increasingly recognized as an important synchronizing mechanism in the brain. At the same time, the biology of central nervous system (CNS) gjs is being unravelled. The pathogenesis of the abnormal neuronal synchrony underlying seizures, formerly thought to be based mainly on chemical synaptic transmission, now includes a role for gap junctional communication. This concept has been strengthened by evidence from several in vitro seizure models, in which pharmacological manipulations of gap junctional communication predictably affect the generation of seizures: blockers diminishing seizures and enhancers increasing the seizures. Evidence for interneurons, coupled in part by gjs, generating synchronous neural network activity including seizures, is presented. Also neuromodelling studies, which have enhanced our ability to understand the functional role that gap junctional communication plays in the generation and maintenance of neural synchrony and seizures, are presented. Gap junctional communication appears to be a promising target for the development of future anticonvulsant therapy.

Animals↗
PubMed2000

Gap junctions, synchrony and seizures.

The old concept that the direct intercellular cytoplasmic connections between neurones participate in the coordination of neuronal activity has gained new relevance, owing to recent theoretical and experimental evidence, particularly with regard to neuronal synchronization and epileptogenesis. Computer simulations demonstrating that neurones synchronize and alter their firing patterns depending on gap-junctional communication, have provided insights into the interactions between electrotonic coupling and cellular and synaptic characteristics. Experimental manipulations of gap-junctional communication support its role in the generation and maintenance of synchronized neuronal firing and seizures. Hence, in addition to chemical transmission, direct electrotonic coupling might contribute to normal and abnormal physiological brain rhythms.

Action Potentials↗
PubMed2000

Oxidative stress is involved in seizure-induced neurodegeneration in the kindling model of epilepsy.

Reactive oxygen species have been implicated in the development of seizures under pathological conditions and linked to seizure-induced neurodegeneration. There has been little direct evidence, however, of free radical production resulting from seizures. Using amygdala-kindled rats, we have examined the generation of reactive oxygen species following seizures, and their possible contribution to seizure development and seizure-induced neuronal loss. The concentrations of two products of free radical-induced lipid peroxidation, malonaldehyde and 4-hydroxy-2(E)-nonenal, were measured using colorimetric assays. Lipid peroxidation was increased in both hemispheres of kindled rats as compared to sham-operated controls. Cell death was also significantly increased in all hippocampal areas. Antioxidants (vitamin E and glutathione) prevented the rise in lipid peroxides and hippocampal neuronal death during kindling, but did not arrest the development of seizures.Thus, epileptiform activity can result in free radical production which may be one of the factors leading to cell death.

Animals↗
PubMed2000

Mitochondrial porin required for ischemia-induced mitochondrial dysfunction and neuronal damage.

The precise molecular events of mitochondrial dysfunction, one of the last steps that irreversibly determines cellular degeneration and death, remain unknown. We introduce a novel strategy to isolate and assess the molecular mechanisms underlying mitochondrial dysfunction. Using an in vitro ischemia model, we obtained evidence for prolonged mitochondrial depolarization in rat organotypic hippocampal brain slices during reperfusion. Then, mitochondria were isolated from brain slices and mitochondrial proteins were purified on a cyclosporin-A affinity column. Cyclosporin-A is the most potent inhibitor of mitochondrial dysfunction, in particular the mitochondrial permeability transition, and therefore we hypothesized that it may interact with proteins involved in the permeability transition after mitochondria were subjected to manipulations that promote this event. Mitochondrial porin was reproducibly eluted from the affinity column using proteins from ischemic brain mitochondria, or from mitochondria exposed to oxidative stress that were used as a positive control. Anti-porin antibodies prevented mitochondrial depolarization and electrophysiological deterioration of hippocampal neurons during hypoxia-reperfusion, as measured by simultaneous fluorescence imaging and whole-cell recordings. These observations provide biochemical and functional evidence that porin is directly involved in mitochondrial dysfunction and neuronal impairment during ischemia-reperfusion, and indicate that porin could be a novel therapeutic target to prevent cellular degeneration.

Animals↗
PubMed2000

Methods to induce primary and secondary traumatic damage in organotypic hippocampal slice cultures.

Organotypic brain slice cultures have been used in a variety of studies on neurodegenerative processes [K.M. Abdel-Hamid, M. Tymianski, Mechanisms and effects of intracellular calcium buffering on neuronal survival in organotypic hippocampal cultures exposed to anoxia/aglycemia or to excitotoxins, J. Neurosci. 17, 1997, pp. 3538-3553; D.W. Newell, A. Barth, V. Papermaster, A.T. Malouf, Glutamate and non-glutamate receptor mediated toxicity caused by oxygen and glucose deprivation in organotypic hippocampal cultures, J. Neurosci. 15, 1995, pp. 7702-7711; J.L. Perez Velazquez, M.V. Frantseva, P.L. Carlen, In vitro ischemia promotes glutamate mediated free radical generation and intracellular calcium accumulation in pyramidal neurons of cultured hippocampal slices, J. Neurosci. 23, 1997, pp. 9085-9094; L. Stoppini, L.A. Buchs, D. Muller, A simple method for organotypic cultures of nervous tissue, J. Neurosci. Methods 37, 1991, pp. 173-182; R.C. Tasker, J.T. Coyle, J.J. Vornov, The regional vulnerability to hypoglycemia induced neurotoxicity in organotypic hippocampal culture: protection by early tetrodotoxin or delayed MK 801, J. Neurosci. 12, 1992, pp. 4298-4308.]. We describe two methods to induce traumatic cell damage in hippocampal organotypic cultures. Primary trauma injury was achieved by rolling a stainless steel cylinder (0.9 g) on the organotypic slices. Secondary injury was followed after dropping a weight (0.137 g) on a localised area of the organotypic slice, from a height of 2 mm. The time course and extent of cell death were determined by measuring the fluorescence of the viability indicator propidium iodide (PI) at several time points after the injury. The initial localised impact damage spread 24 and 67 h after injury, cell death being 25% and 54%, respectively, when slices were kept at 37 degrees C. To validate these methods as models to assess neuroprotective strategies, similar insults were applied to slices at relatively low temperatures (30 degrees C), which is known to be neuroprotective [F.C. Barone, G.Z. Feuerstein, R.F. White, Brain cooling during transient focal ischaemia provides complete neuroprotection, Neurosci. Biobehav. Rev. 1, 1997, pp. 31-44; V.M. Bruno, M.P. Goldberg, L.L. Dugan, R.G. Giffard, D.W. Choi, Neuroprotective effect of hypothermia in cortical cultures exposed to oxygen glucose deprivation or excitatory aminoacids, J. Neurochem. 4, 1994, pp. 387-392; G.C. Newman, H. Qi, F.E. Hospod, K. Grundhmann, Preservation of hippocampal brain slices with in vivo or in vitro hypothermia, Brain Res. 1, 1992, pp. 159-163; J.Y. Yager, J. Asseline, Effect of mild hypothermia on cerebral energy metabolism during the evolution of hypoxic ischaemic brain damage in the immature rat, Stroke, 5, 1996, pp. 919-925.]. Low temperature incubation significantly reduced cell death, now being 9% at 24 h and 14% at 67 h. Our results show that these models of moderate mechanical trauma using organotypic slice cultures can be used to study neurodegeneration and neuroprotective strategies.

Animals↗
PubMed1998

Slow oscillations (</=1 Hz) mediated by GABAergic interneuronal networks in rat hippocampus.

Perfusion of rat brain slices with low millimole CsCl elicits slow oscillations of </=1 Hz in hippocampal CA1 pyramidal neurons. These oscillations are GABAA receptor-mediated hyperpolarizations that permit a coherent fire-pause pattern in a population of CA1 neurons. They can persist without the activation of ionotropic glutamate receptors but require adenosine-dependent inhibition of glutamate transmission. In response to external Cs+, multiple interneurons in the CA1 region display rhythmic discharges that correlate with the slow oscillations in CA1 pyramidal neurons. The interneuronal discharges arise spontaneously from the resting potential, and their rhythmicity is regulated by periodic, GABAA receptor-mediated hyperpolarizations. In addition, interneurons show periodic partial spikes and neurobiotin coupling, and applications of known gap junctional uncouplers interrupt the Cs+-induced slow rhythm in both CA1 pyramidal neurons and interneurons. We propose that these slow oscillations originate from a GABAergic interneuronal network that interacts through reciprocal inhibition and possibly gap junctional connection.

2-Amino-5-phosphonovalerate↗
PubMed1998

Changes in membrane and synaptic properties of thalamocortical circuitry caused by hydrogen peroxide.

Free radical (FR) production was linked to the generation of epileptiform activity. We performed electrophysiological recordings in rat thalamocortical slices to investigate the effects of FRs on the intrinsic and synaptic properties of thalamic and cortical neurons. Whole cell recordings from identified cortical pyramidal neurons and thalamic neurons of the ventrobasal nucleus revealed that exposure to the FR-forming agent H2O2 (2.5 mM) decreased gamma-aminobutyric acid-A- and gamma-aminobutyric acid-B-mediated inhibition to 35.3 +/- 13.4% and 13.7 +/- 4.4% (means +/- SE) of control in cortical neurons and to 41.8 +/- 14.8% and 33.6 +/- 11.6% of control in thalamic neurons. H2O2 application increased excitatory transmission in thalamic neurons to 162.9 +/- 29.6% of control but caused no change in cortical neurons. H2O2 altered significantly the characteristic low-pass filter behavior of cortical and thalamic cells as determined by their input impedances. After 35 min of superfusion, the impedance of cortical neurons decreased by 67.0 +/- 14.5%, and thalamic decreased by 76.3 +/- 2.7% for the frequencies in the range 1-50 Hz while remaining constant for frequencies > 200 Hz. Neuronal hyperexcitability was manifested during H2O2 exposure by continuous firing and long depolarizing shifts in response to extracellular stimulation in both thalamocortical and cortical neurons only in slices preserving thalamocortical connections. In slices with severed thalamocortical connections, cortical neurons did not show signs of hyperexcitability. These observations indicate that FRs could promote hyperexcitability of thalamocortical circuits by altering the balance between excitation and inhibition and by transforming the characteristic low-pass filter behavior into a flat band-pass filter.

2-Amino-5-phosphonovalerate↗
PubMed1997

In vitro ischemia promotes glutamate-mediated free radical generation and intracellular calcium accumulation in hippocampal pyramidal neurons.

Ischemia-induced cell damage studies have revealed a complex mechanism that is thought to involve glutamate excitotoxicity, intracellular calcium increase, and free radical production. We provide direct evidence that free radical generation occurs in rat CA1 pyramidal neurons of organotypic slices subjected to a hypoxic-hypoglycemic insult. The production of free radicals is temporally correlated with intracellular calcium elevation, as measured by injection of fluo-3 in individual pyramidal cells, using patch electrodes. Free radical production (measured as changes in the fluorescence emission of dihydrorhodamine 123) peaked during reoxygenation and paralleled rising intracellular calcium. Electrophysiological whole-cell recordings revealed membrane potential depolarization and decreased input resistance during the ischemic insult. Glutamate receptor blockade resulted in decreased free radical production and markedly diminished intracellular calcium accumulation, and prevented neuronal depolarization and input resistance decrease during the ischemic episode. These results provide evidence for a direct involvement of glutamate in oxidative damage resulting from ischemic episodes.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1997

Mechanisms of electrical coupling between pyramidal cells.

Direct electrical coupling between neurons can be the result of both electrotonic current transfer through gap junctions and extracellular fields. Intracellular recordings from CA1 pyramidal neurons of rat hippocampal slices showed two different types of small-amplitude coupling potentials: short-duration (5 ms) biphasic spikelets, which resembled differentiated action potentials and long-duration (>20 ms) monophasic potentials. A three-dimensional morphological model of a pyramidal cell was employed to determine the extracellular field produced by a neuron and its effect on a nearby neuron resulting from both gap junctional and electric field coupling. Computations were performed with a novel formulation of the boundary element method that employs triangular elements to discretize the soma and cylindrical elements to discretize the dendrites. An analytic formula was derived to aid in computations involving cylindrical elements. Simulation results were compared with biological recordings of intracellular potentials and spikelets. Field effects produced waveforms resembling spikelets although of smaller magnitude than those recorded in vitro. Gap junctional electrotonic connections produced waveforms resembling small-amplitude excitatory postsynaptic potentials. Intracellular electrode measurements were found inadequate for ascertaining membrane events because of externally applied electric fields. The transmembrane voltage induced by the electric field was highly spatially dependent in polarity and wave shape, as well as being an order of magnitude larger than activity measured at the electrode. Membrane voltages because of electrotonic current injection across gap junctions were essentially constant over the cell and were accurately depicted by the electrode. The effects of several parameters were investigated: 1) decreasing the ratio of intra to extracellular conductivity reduced the field effects; 2) the tree structure had a major impact on the intracellular potential; 3) placing the gap junction in the dendrites introduced a time delay in the gap junctional mediated electrotonic potential, as well as deceasing the potential recorded by the somatic electrode; and 4) field effects decayed to one-half of their maximum strength at a cell separation of approximately 20 micron. Results indicate that the in vitro measured spikelets are unlikely to be mediated by gap junctions and that a spikelet produced by the electric field of a single source cell has the same waveshape as the measured spikelet but with a much smaller amplitude. It is hypothesized that spikelets are a manifestation of the simultaneous electric field effects from several local cells whose action potential firing is synchronized.

Action Potentials↗
PubMed1996

Development of astrocytes and neurons in cultured brain slices from mice lacking connexin43.

Astrocyte and neuronal development was investigated in organotypic brain slice cultures from mouse fetuses with a null mutation in the connexin43 gene. Astrocyte morphology and electrical properties were indistinguishable in null mutant slices and control slices but at 18 days in vitro astrocyte density in the central regions of the null mutant slices was significantly higher than in control slices. Neuronal development assessed morphologically and electrophysiologically appeared normal in the mutant slices. These results suggest that intercellular communication mediated through connexin43 is not essential for the development of astrocytes and neurons but may play a role in regulating astrocytic migration.

Animals↗
PubMed1996

Development of firing patterns and electrical properties in neurons of the rat ventrobasal thalamus.

The electrophysiological properties of thalamic neurons of the rat ventrobasal complex (VB) in vitro were studied during early postnatal development. Current clamp recordings using the whole cell patch clamp method revealed that immature thalamic neurons had less negative membrane potential and higher input resistance than mature neurons. One of the most remarkable differences was the absence of spike bursts riding on the low threshold calcium spike (LTS) in VB neurons before postnatal day 12 (P12). Action potentials recorded from immature neurons had longer duration than those of mature cells and were followed by a longer afterhyperpolarization (spike-ahp). The spike-ahp became shorter as maturation progressed, reaching mature characteristics around P12, coinciding with the appearance of spike bursting on the LTS. The calcium activated potassium conductance, IC, played a prominent role in the spike-ahp in immature neurons. In conclusion, the major differences in intrinsic membrane properties of VB neurons occur during the first 12 postnatal days. The appearance of spike bursting riding on the LTS at P12 is consistent with the emergence of synchronized thalamocortical oscillations in rats around that age.

Action Potentials↗