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M Avoli

Publications and source records attributed to M Avoli.

At least 73 records · Page 4Linked to original sources
PubMed1996

Anoxia blocks the presynaptic control of GABA release at inhibitory terminals in the rat hippocampus.

Field potential and (K+)o recordings were made in rat hippocampal slices during application of 4-aminopyridine (50 microM) and ionotropic excitatory amino acid receptor antagonists, to establish whether anoxia modified the mechanisms that regulate GABA release from inhibitory interneurons. Synchronous, negative-going field potentials (amplitude = 1.41 +/- 0.64 mV, mean +/- S.D.; interval = 40.9 +/- 15.7 s; n = 10) occurred spontaneously in the CA3 stratum radiatum under control conditions. These events were associated with transient elevations in (K+)o (peak values = 5.3 +/- 0.7 mM; duration = 23.4 +/- 3.5 s; n = 5 slices) and were abolished by the GABAA, receptor antagonist bicuculline methiodide (10 microM; n = 5), the GABAB receptor agonist baclofen (100 microM; n = 6) or the mu-opioid receptor agonist (D-Ala2-N-Me-Phe, Gly-ol)enkephalin (10 microM; n = 4). Hence they represented monosynaptic field inhibitory postsynaptic potentials. Brief (4-5 min) episodes of anoxia induced a reversible, slow elevation of the baseline (K+)o to 5.2 +/- 0.3 mM (n = 5), while the rate of the field inhibitory postsynaptic potentials increased by an average of 130.7% (n = 10). Oxygen interruption during application of either baclofen (n = 6) or (D-Ala2-N-Me-Phe,Gly-ol)enkephalin (n = 4) blocked the depressant action of both drugs on the field inhibitory postsynaptic potential. These findings demonstrate that hippocampal monosynaptic field inhibitory postsynaptic potentials are resistant to brief anoxic episodes and that oxygen deprivation readily blocks the presynaptic control of GABA release exerted by GABAB and mu-opioid receptors at inhibitory interneuron terminals.

4-Aminopyridine↗
PubMed1996

Neuronal migration disorders and epilepsy: a morphological analysis of three surgically treated patients.

Despite the increasing number of patients affected by neuronal migration disorders (NMDs) recently diagnosed in vivo by means of magnetic resonance imaging (MRI), few detailed data on the correlation between the neuroradiological and the anatomical features in the single NMD case are available. The present paper reports a combined cytoarchitectural and immunocytochemical analysis, by means of antisera recognizing specific neuronal and glial markers, of three MRI diagnosed NMD patients surgically treated for the relief of intractable seizures. The first case was a giant subcortical nodular heterotopia of morphologically normal neurons lacking any type of cortical lamination. The second case was a layered polymicrogyria with an abnormal amount of ectopic neurons in the underlying white matter. The third case was a focal cortical dysplasia characterized by a dramatic disruption of the normal cortical layering associated with marked cytological abnormalities. The present data demonstrate that the macroscopical and microscopical brain abnormalities can be markedly different in different NMD subtypes, and suggest that different anatomical substrates can underlie the intrinsic hyperexcitability of these brain malformations. The relevance of further prospective clinico-morphological studies for a better understanding of the mechanisms determining the development of these brain malformations is underlined.

Brain↗
PubMed1996

GABA-mediated synchronous potentials and seizure generation.

This article summarizes findings related to a synchronous, GABA-mediated potential that may contribute to the initiation and spread of epileptiform discharges within the brain. This phenomenon is observed in cortical structures such as the hippocampus, the entorhinal cortex, and the neocortex during application of low concentrations of 4-aminopyridine and is characterized at the intracellular level by a long-lasting membrane depolarization. The synchronous, GABA-mediated potential continues to occur after blockade of excitatory synaptic transmission and relays on the synchronous firing of inhibitory interneurons and consequent activation of postsynaptic (mainly type A) GABA receptors leading to a transient elevation of [K+]O. Studies performed in young rat hippocampus indicate that the synchronous, GABA-mediated potential may play a role in initiating ictal discharges under normal conditions (i.e., when excitatory amino acid receptors are operant). Moreover, a similar phenomenon may also occur in adult rat entorhinal cortex. These findings therefore indicate a novel role that is played by GABAA receptors in limbic structures. The ability of this synchronous GABA-mediated potential to propagate in the absence of excitatory synaptic transmission may also be relevant for the propagation of synchronous activity outside conventional neuronal-synapse dependent pathways. This condition may occur in brain structures with neuronal loss and consequent disruption of normal excitatory synaptic connections such as mesial limbic structures of temporal lobe epilepsy patients with Ammon's horn sclerosis.

Action Potentials↗
PubMed1995

Subthreshold membrane-potential oscillations in immature rat CA3 hippocampal neurones.

Subthreshold membrane potential oscillations (MPOs) were recorded intracellularly in 31 of 43 (>70%) immature CA3 hippocampal neurones (from 3-17 days postnatally). MPOs (3-5 mV, 3-15 Hz) occurred at resting membrane potential (RMP) in 20 of 31 neurones, or following depolarization (11 of 31 neurones); with sufficient depolarization spontaneous action potentials (APs) were generated from the positive-going phase of MPOs. In all cells, MPOs were blocked by steady membrane hyperpolarization. Tetrodotoxin abolished MPOs (n = 4); Co(2+) markedly reduced them (n = 3), and tetraethylammonium, added in the presence of TTX, revealed lower frequency oscillatory activity (n = 2). We conclude that subthreshold MPOs in immature hippocampus, possibly linked to theta rhythm generation and memory acquisition, depend on voltage-dependent Na+ electrogenesis and they might be additionally controlled by Ca(2+) and K+ conductances.

Animals↗
PubMed1995

Extracellular potassium elevations in the hippocampus of rats with long-term pilocarpine seizures.

Pilocarpine injection into rodents leads to the development of chronic limbic seizures that follow an initial status epilepticus and a seizure-free interval. It has been proposed that a decreased efficacy of the mechanisms that buffer the extracellular concentration of K+ ([K+]o) leads to an increase in seizure susceptibility. Therefore, we analyzed the changes in [K+]o associated with the synchronous activity induced by 4-aminopyridine (4AP) in hippocampal slices obtained from control and pilocarpine-treated rats. At all recording sites (i.e. stratum radiatum of the CA1 and CA3 subfields, and hilus of the dentate gyrus), the amplitude of GABA-mediated synchronous field potentials induced by 4AP, as well as the associated [K+]o increases, were significantly reduced in slices obtained from the pilocarpine-treated rats. In the control group, the field-potential amplitudes reached 1 mV (i.e. 1.7 +/- 0.3 mV in CA1, 0.93 +/- 0.2 mV in CA3, and 1.03 +/- 0.12 mV in the hilus; mean +/- SEM), while the accompanying rises in [K+]o exceeded 4 mM (i.e. 4.17 +/- 0.15 mM in CA1, 4.04 +/- 0.12 mM in CA3, 4.04 +/- 0.11 mM in the hilus) from a baseline of 3.25 mM. The corresponding values in slices from the pilocarpine-treated group were rarely greater than 0.4 mV (i.e. 0.3 +/- 0.09 mV in CA1, 0.27 +/- 0.03 mV in CA3 and 0.38 +/- 0.06 mV in the hilus), and larger than 3.6 mM (i.e. 3.63 +/- 0.04 mM in CA1, 3.64 +/- 0.03 mM in CA3 and 3.60 +/- 0.04 mM in the hilus) from a similar baseline value. With pilocarpine, the rate of occurrence of the GABA-mediated potential significantly decreased from 0.035 to 0.016 s-1. Since the rises in [K+]o decreased rather than increased and their overall duration was unchanged (possibly reflecting cell loss), we conclude that a modification of [K+]o buffering capacity is unlikely to account for the appearance of in vivo seizures in the pilocarpine model of epilepsy.

4-Aminopyridine↗
PubMed1995

Synchronous potentials and elevations in [K+]o in the adult rat entorhinal cortex maintained in vitro.

Extracellular field-potential recordings and measurements of the extracellular concentration of potassium ([K+]o) were made in layers II and III of the adult rat entorhinal cortex in a slice preparation. Two types of spontaneous, synchronous potentials were induced by the convulsant drug 4-aminopyridine (4AP, 50 microM). The first type was seen in all slices (n = 19) and consisted of a negative-going field potential that lasted 0.5-3.5 s and occurred at rates of 0.013-0.13 Hz. This event was accompanied by an elevation in [K+]o that attained peak values of 4.0-7.6 mM. The second type was reminiscent of ictal epileptiform discharges and was recorded in 6 of 19 slices; it lasted 21-190 s, recurred at 0.001-0.003 Hz and was associated with [K+]o increases that had peak values of 14-17 mM. Whenever such an ictal discharge occurred, it was closely preceded and thus appeared to be initiated by the first type of field potential. Perfusion with N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-3-(2-carboxy-piperazine-4-yl)propyl-1-phosphonate (CPP; 10 microM) abolished the ictal discharge (n = 4). This pharmacological procedure did not abolish the negative-going potentials that continued to occur during further application of the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM; n = 4). These glutamatergic-independent potentials were, however, blocked by the GABBAA-receptor antagonist bicuculline methiodide (10 microM, n= 3). Thus, as in hippocampus, 4AP can induce in the entorhinal cortex a synchronous GABA-mediated potential that is resistant to excitatory amino acid antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗
PubMed1995

Extracellular magnesium and anticonvulsant effects of valproate in young rat hippocampus.

Extracellular field potential recordings were made in CA3 subfield of hippocampal slices from rats aged 11-22 days. In these experiments, we analyzed the effects induced by modifying [Mg2+] in the medium (1 or 2 mM) on (a) 4-aminopyridine (4-AP, 50 microM)-induced synchronous events (including ictal- and interictal-like epileptiform discharges as well as gamma-aminobutyric acid (GABA)-mediated potentials), and (b) the changes induced by the antiepileptic drug (AED) valproate (VPA 2 mM) on such activities. Changing [Mg2+] from 1 to 2 mM induced age-dependent effects consisting of reduction in rate of occurrence of ictal-like discharges at 11-13 days (55% reduction, p < 0.005) and 14-16 days (46% reduction, p < 0.025) postpartum. At any age, the rate of occurrence and the amplitude of the GABA-mediated synchronous potentials tended to decrease in 1 mM [Mg2+]. Similar effects were noted when changes in [Mg2+] were made during continuous application of the competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor DL-2-amino-5-phosphonovalerate (APV 50 microM). As previously reported, interictal and ictal discharges were blocked by addition of VPA to medium containing 2 mM [Mg2+]. Such an effect was not observed when [Mg2+] was decreased to 1 mM. In 1 mM, but not in 2 mM [Mg2+], VPA increased the amplitude of GABA-mediated synchronous potentials. Our results indicate that [Mg2+] plays a role in modulating occurrence of 4-AP-induced ictal activity and that it can influence the effects of VPA in this in vitro model of epileptogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1995

GABAA-mediated inhibition and in vitro epileptogenesis in the human neocortex.

1. We made intracellular and extracellular field potential recordings and ion-selective measurements of extracellular Ca2+ concentration ([Ca2+]o) and extracellular K+ concentration ([K+]o) in human neocortical slices that were obtained in the course of epilepsy surgery. Slices were maintained in vitro at 34-35 degrees C and were perfused with Mg(2+)-free artificial cerebrospinal fluid (ACSF). 2. Spontaneous field potential epileptiform discharges (duration = 2.5-80 s) occurred in most of the slices studied (approximately 60%) after 1.5-2 h of perfusion with Mg(2+)-free ACSF. Intracellular recordings from regular-spiking neocortical neurons showed that epileptiform events consisted of large-amplitude (15-30 mV) depolarizing shifts that were capped by bursts of fast action potentials. A decrease in [Ca2+]o (change in [Ca2+]o = 0.02-0.17 mM, 0.07 +/- 0.046 mM, mean +/- SD, from a baseline of 1.8 mM, n = 10 slices) and an increase in [K+]o (change in [K+]o = 0.5-3.8 mM, 1.6 +/- 1.24 mM, from a baseline of 3.25 mM, n = 10) were associated with each epileptiform discharge. 3. The epileptiform activity induced by Mg(2+)-free ACSF was abolished by bath application of antagonists of the N-methyl-D-aspartate (NMDA) receptor. This procedure also blocked the appearance of spreading depression-like episodes. By contrast, the rate of occurrence of epileptiform discharges was not significantly modified by antagonizing non-NMDA receptors. 4. We also observed spontaneous, rhythmic potentials of positive polarity during perfusion of Mg(2+)-free ACSF; the potentials became hyperpolarizing when the neuron membrane was made less negative than -75 mV with intracellular injection of depolarizing current, and they were decreased or abolished during application of the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline methiodide (BMI). The rate of occurrence and/or the amplitude of these presumably GABAA-mediated events decreased approximately 2 s before the onset of each epileptiform discharge. 5. Application of BMI prolonged the epileptiform discharges while decreasing their rate of occurrence. These changes were also accompanied by an increase in the amplitude of the epileptiform field potential DC shift, whereas the concomitant decreases in [Ca2+]o and increases in [K+]o became more pronounced than in control Mg(2+)-free medium (31.2% and 42.8%, respectively, n = 10 slices). 6. Intracellular analysis of regular-spiking neurons in slices that did not generate spontaneous epileptiform discharges after > 2 h of perfusion with Mg2+-free ACSF showed all-or none, variable-latency epileptiform bursts that were induced by high-strength focal extracellular stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

Bicuculline↗
PubMed1995

Seizure-like discharges recorded in human dysplastic neocortex maintained in vitro.

Application of the convulsant drug 4-aminopyridine (50 to 100 microM) induced spontaneous seizure-like discharges (duration = 76.3 +/- 46.8 sec, mean +/- SD; interval of occurrence = 225.2 +/- 87.9 sec) in slices of neocortex obtained from patients with a diagnosis of focal neuronal migration disorders during neurosurgical procedures for relief of drug-resistant seizures. Similar epileptiform discharges could also be elicited in these slices by single-shock stimuli delivered in the underlying white matter or within the gray matter. By contrast, neocortical slices obtained from patients suffering from temporal lobe epilepsy (which is characterized by Ammon's horn sclerosis but relatively normal neocortex) did not generate any epileptiform activity during 4-aminopyridine application. Thus, our study is the first to provide experimental evidence for the intrinsic epileptogenicity that characterizes neuronal migration disorders.

4-Aminopyridine↗
PubMed1994

Control of 4-aminopyridine-induced synchronous activity by adenosine A1 and mu-opioid receptor agonists in adult rat hippocampus.

In the presence of 4-aminopyridine (4AP, 50 microM) two types of spontaneous field potentials can be recorded in the CA3 stratum radiatum of adult rat hippocampal slices. First, epileptiform interictal discharges (0.85 +/- 0.25 Hz) that are blocked by excitatory amino acid ionotropic receptor antagonists. Second, negative-going synchronous potentials (0.036 +/- 0.015 Hz) which are solely abolished by application of bicuculline methiodide (BMI). Bath application of the specific adenosine A1 receptor agonist, N6-(L-2-phenylisopropyl) adenosine (L-PIA), reduced the frequency of interictal discharges in a dose-dependent manner (IC50 = 8.75 microM; n = 9 slices) and this effect was reversed by the specific adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 microM; n = 3 slices). L-PIA did not affect the frequency of occurrence of the negative-going field potential during application of excitatory amino acid receptor antagonists. This BMI-sensitive event was depressed, however, by application of the mu-opioid receptor agonist [D-Ala2-N-Me-Phe4,Gly5(5)-ol]enkephalin (DAGO, 10 microM; 15.1 +/- 8.7% of rate in control; n = 6 slices), an effect that was antagonized by naloxone (20 microM). Our results indicate that L-PIA reduces the 4AP-induced epileptiform activity through the activation of adenosine A1 receptors. This procedure does not influence the BMI-sensitive field potential, which is abolished, however, by DAGO. Thus, our findings support the hypothesis that the BMI-sensitive potential is due to the presynaptic release of GABA from interneurons.

4-Aminopyridine↗
PubMed1994

Interictal discharges in the hippocampus of rats with long-term pilocarpine seizures.

Systemic administration of pilocarpine to adult rats induces an acute status epilepticus followed by spontaneous recurrent seizures after a 1-2-week silent period. We recorded field potentials in hippocampal slices obtained from rats with spontaneous recurrent seizures after pilocarpine-induced status. The frequency of the interictal discharges induced in these slices by 4-aminopyridine (4AP) was reduced and their duration was increased. Cutting the Schaffer collaterals caused interictal discharges in CA1 to disappear in normal rats and in rats 3 weeks after pilocarpine-induced status. However, 12 weeks after pilocarpine, these discharges remained in CA1 after such a cut but occurred at a lower frequency. These findings show that in rat hippocampi with a lesion similar to that of human Ammon's horn sclerosis some electrophysiological features of 4AP-induced interictal discharges are altered in comparison to those induced in normal hippocampi.

4-Aminopyridine↗
PubMed1994

Extracellular free potassium during synchronous activity induced by 4-aminopyridine in the juvenile rat hippocampus.

Field potential recordings and measurements of the extracellular concentration of free K+ ([K+]o) were made in the stratum radiatum of the CA3 subfield of hippocampal slices that were obtained from 12- to 17-day-old rats. Spontaneous, synchronous field potentials were recorded in the presence of the convulsant drug 4-aminopyridine (4AP, 50 microM). They consisted of interictal- (duration = 0.2-1.2 s; rate of occurrence = 0.3-1.3 Hz) and ictal-like epileptiform discharges (8-40 s; 4-38.10(-3) Hz), as well as large amplitude, negative-going potentials that preceded the onset of the ictal-like event. Such a temporal correlation suggested that the negative-going potential might facilitate the onset of ictal-like activity. Interictal- and ictal-like discharges were abolished by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM), while the negative-going potential was selectively blocked by bicuculline methiodide (BMI, 10 microM). Hence it was presumably due to the activation of GABAA receptors. [K+]o increased up to 12.5 mM (7.9 +/- 2.7 mM, mean +/- S.D.) from a resting value of 3.25 mM during the BMI-sensitive potentials (which also corresponded to the onset of ictal-like events), and after a decline to approximately 5 mM it remained elevated throughout the ictal event. Small, transient increases in [K+]o (up to 3.7 mM) could be seen during each interictal-like event. Following blockade of interictal- and ictal-like discharges by CNQX increases in [K+]o (up to 11 mM; 7.3 +/- 2.1; half-width = 7.2 +/- 2.3 s) still accompanied the BMI-sensitive negative-going potentials.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗
PubMed1994

Age-dependent appearance of synaptic currents in rat neocortical neurons in culture.

Rat neocortical neurons grown in dissociated cell culture were recorded with the whole-cell patch-clamp technique. Spontaneous inward currents were observed in cells that were held at a membrane potential of -80 mV in medium containing tetrodotoxin and Cd2+. These currents displayed amplitudes up to 140 pA and rise time of 1.8 +/- 0.2 ms (mean +/- SD, n = 15). They reversed near 0 mV and showed no voltage-dependent frequency of occurrence. Hence, they were presumably due to spontaneous release of transmitter. The inward currents appeared around day 10 in culture and were detected up to 4 weeks. When cells of different ages were compared, the maximal probability of recording these inward events occurred at around 3 weeks in culture. The inward currents were not reduced by application of bicuculline methiodide which is a competitive antagonist of the GABAA receptor, but were blocked by the broad-spectrum glutamate receptor antagonist kynurenic acid. Moreover, spontaneous inward events were not affected by DL-2-aminophosphono-valerate (NMDA receptor antagonist) but disappeared following application of the non-NMDA receptors antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Our observations indicate that the inward currents represent miniature synaptic events that are primarily mediated by non-NMDA excitatory amino acid receptor subtypes. Furthermore, our findings indicate that they develop over time and are not present in neurons that are grown in culture for less than 10 days.

2-Amino-5-phosphonovalerate↗
PubMed1994

Electrophysiological and repetitive firing properties of neurons in the superficial/middle layers of the human neocortex maintained in vitro.

Conventional intracellular recordings were made from neurons located in the superficial/middle layers of human temporal neocortical slices obtained from patients undergoing neurosurgical procedures for the treatment of epilepsy or brain tumour. In most of the neurons, inward membrane rectification was observed when the cell was depolarized or hyperpolarized from rest by intracellular injection of positive or negative current pulses. Bath application of tetrodotoxin abolished the depolarizing inward rectification, but not the "anomalous rectification" in the hyperpolarizing direction. Single action potential firing was followed by a fast afterhyperpolarization, a depolarizing afterpotential and a medium afterhyperpolarization, while a slower afterhyperpolarization was seen following repetitive firing. Blockade of Ca2+ channels with Cd2+ diminished all three types of afterhyperpolarization. Although the repetitive firing pattern in all cells indicated that they discharge in a regular-spiking fashion, 63% of the cells fired tonically in the initial part of discharge, while the remaining 37% of the cells fired phasically. Frequency-current plot for the initial interspike intervals during long depolarizing pulses revealed primary and secondary ranges of firing. Spike frequency adaptation was also observed. In conclusion, our experiments indicate that human neocortical cells in the superficial/middle layers display electrophysiological characteristics that are similar to those described in rodent and feline neocortices.

Action Potentials↗
PubMed1994

Potassium channel activators counteract anoxic hyperexcitability but not 4-aminopyridine-induced epileptiform activity in the rat hippocampal slice.

The K+ channel activators diazoxide and cromakalim were investigated for effects on 4-aminopyridine (4AP)-induced epileptiform activity in adult rat hippocampal slices maintained in vitro. Under normal conditions of oxygenation, 4AP (50 microM) induced two types of field potentials in extracellular recordings from the CA3 stratum radiatum (apical dendritic region): epileptiform interictal discharge-like events occurring at a frequency of 0.75 +/- 0.36 Hz and long-lasting negative-going potentials mediated by GABA receptor activation that occurred at 0.03 +/- 0.01 Hz (n = 36 slices). Neither diazoxide (0.65-1.3 mM, n = 21 slices) nor cromakalim (50-200 microM, n = 6 slices) altered these two types of discharge. Brief periods of anoxia (4-6 min) reduced the frequency of the 4AP-induced interictal-like events (from 0.75 +/- 0.36 Hz to 0.19 +/- 0.15 Hz, n = 20 slices). In 45% of the experiments, the depressant effect of anoxia was preceded by a period of hyperexcitability consisting of a transient (36.1 +/- 12.9 sec) increase in the frequency of interictal-like events riding on a negative-going DC shift (n = 9 slices). Both responses to anoxia were reversible upon reoxygenation. In contrast, the rate of occurrence of the GABA-mediated potentials was unaffected by the anoxic episodes. Perfusion with cromakalim (n = 4 slices) or diazoxide (n = 5 slices) abolished the initial period of hyperexcitability produced by O2 deprivation but did not alter the subsequent depression of activity. Our experiments indicate that the K+ channel activators can prevent the initial hyperexcitability produced by anoxia, but do not influence 4AP-induced epileptiform activity in normoxic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗
PubMed1994

Pharmacology and electrophysiology of a synchronous GABA-mediated potential in the human neocortex.

Spontaneous synchronous field potentials of negative polarity (duration = 200-700 ms, inter-event interval = 9.1 +/- 2.9 s; n = 27 slices) were recorded, during application of 4-aminopyridine (50 microM), from the superficial/middle layers of slices of human neocortex obtained in the course of neurosurgery for the relief of intractable seizures. The negative-going field potential corresponded to an intracellular long-lasting (duration = 200-1600 ms) depolarization that could be preceded by preceded by an excitatory postsynaptic potential-hyperpolarizing inhibitory postsynaptic potential sequence and followed by a long-lasting hyperpolarization. This synchronous activity continued to occur following blockade of excitatory synaptic transmission by excitatory amino acid receptor antagonists, but was greatly reduced and eventually disappeared during application of the GABAA receptor antagonist bicuculline methiodide. Simultaneous extracellular recordings from three sites in the slice located along an axis parallel to the pia showed that successive synchronous field potentials could originate from any of the three areas. They invaded the other two sites in c. 35.5% of the cases, while propagation to another site only or no propagation at all was observed, respectively, in 44.4% and 20% of instances. The velocity of lateral propagation of the synchronous field potential was 7.9 +/- 2.5 mm/s (range = 4.5-11.8 mm/s, n = 6). The modalities of origin and propagation remained the same after blockade of excitatory amino acid receptors. Under these conditions, however, there was a higher incidence of non-propagation and the velocity was significantly lower than in control (5.6 +/- 1.9 mm/s; range = 2.8-7.7 mm/s, n = 6). These data indicate that, in the human neocortex, 4-aminopyridine can reveal a synchronous field potential that correlates with an intracellular long-lasting depolarization and is mainly due to the activation of postsynaptic GABAA receptors. The action of excitatory amino acid receptors is not necessary for the generation and propagation of these GABA-mediated potentials. We propose that this potential represents a novel mechanism for synchronization and spread of neuronal activity, including seizure-like discharges in the human neocortex.

2-Amino-5-phosphonovalerate↗
PubMed1994

Quantitative evaluation of neuronal loss in the dorsal hippocampus in rats with long-term pilocarpine seizures.

Systemic administration of the cholinergic agonist pilocarpine (350-400 mg/kg, i.p.) to rats induces acute behavioral and EEG status epilepticus followed by apparent complete neurological recovery. In rats receiving higher doses of pilocarpine (i.e., 380-400 mg/kg), recurrent seizures reappear 2-2.5 weeks later and continue to occur as long as the rats are kept alive. Stereological estimates of neurons in regions CA1, CA3 and the dentate granule cell layer in the dorsal hippocampus show a dose-dependent neuronal loss in the CA3 and CA1 subregions. The granule cell layer of the dentate gyrus is not affected. No progressive neuronal loss was observed in the regions studied after 3, 6 and 12 weeks during which the animals displayed spontaneous recurrent seizures. The temporal profile of the epileptic condition induced by pilocarpine and the resulting pattern of neuronal loss in the rat hippocampus are similar to those seen in many cases of human temporal lobe epilepsy. The neuronal loss is dose-dependent and primarily results from the acute pilocarpine-induced seizures as chronic seizures do not produce any measurable additional cell loss in the regions examined in the experimental model used in this study.

Animals↗