Biomedical subjects

C Psarropoulou

Publications and source records attributed to C Psarropoulou.

14 recordsLinked to original sources

PubMed1996

Developmental features of 4-aminopyridine induced epileptogenesis.

4-Aminopyridine (4-AP, 50 microM), perfused in rat hippocampal slices from postnatal days 2-30 (P2-P30), induced in the CA3 area the appearance of spontaneous epileptiform discharges, short (interictal-like) and sustained (ictal-like), as well as slow potential. The duration of epileptiform discharges decreased and their rate of occurrence (frequency) increased with maturation: their duration during the 1st postnatal week was 4-6 times longer and their frequency 5 times lower, compared to those of the 4th postnatal week. Ictal discharges gradually disappeared at the end of the 4th postnatal week. Spontaneous synchronous activity-as a whole-often appeared in clusters separated by equal or longer length inactive periods, during the first two postnatal weeks. At the same period, ictal discharges were often followed by repetitive afterdischarges, forming sequences which lasted 0.7-1.5 min. Sectioning experiments showed that epileptiform discharges were generated in CA3, and their presence in CA1 depended on the integrity of CA1-CA3 synaptic connections. In conclusion, these findings demonstrate that (i) immature CA3 can generate synchronous epileptiform discharges as early as P2, (ii) such discharges are longer lasting and more complex during the early developmental stages and (iii) there are two time points (end of 2nd, end of 4th postnatal weeks), when maturational changes alter the epileptogenic properties of immature hippocampus.

4-Aminopyridine↗

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↗

PubMed1993

4-Aminopyridine-induced spreading depression episodes in immature hippocampus: developmental and pharmacological characteristics.

Spontaneous spreading depression episodes were studied in CA1 and CA3 areas of immature hippocampal slices (two to 30 days postnatally) during 4-aminopyridine (50 microM) perfusion. Spreading depression occurred in the CA3 area of 34% of all slices tested (two to 30 days postnatally). The duration and frequency of the spreading depression field potentials changed with development. In the CA3 area, their duration decreased from 169 +/- 22 s (n = 17, postnatal days to to 10) to 55 +/- 7 s (n = 10, postnatal days 21-30), their rate of occurrence increased from four episodes per hour (0.0011 +/- 0.0001 Hz, n = 11, postnatal days two to 10) to 6.5 episodes per hour (0.0018 +/- 0.0003 Hz, n = 8, postnatal days 21-30), while their amplitude remained stable (10-30 mV). Spreading depression d.c. potential shift originated closer to CA1 than CA3. Furthermore, spreading depression field potentials had greater magnitude (amplitude and duration) in CA1. Spreading depressions were reversibly blocked by the N-methyl-D-aspartate receptor antagonist 3,3-(2-carboxy-piperazine-4-yl)-propyl-1-phosphonate (CPP, 1-5 microM, n = 15), but were not affected by 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX, 2-5 microns, n = 11), which is a non-N-methyl-D-aspartate receptor antagonist. The GABAA receptor antagonist bicuculline methiodide (3-10 microM) initially favored and then blocked spreading depression in 79% of the slices tested (n = 16). In addition, bicuculline impaired spreading depression propagation from CA1 to CA3. 4-Aminopyridine also induced the appearance of other types of spontaneous activity, such as ictal and interictal-like epileptiform discharges. The effects of 3,3-(2-carboxy-piperazine-4-yl)-propyl-1-phosphonate, 6-cyano-7-nitro-quinoxaline-2,3-dione and bicuculline on epileptiform activity were opposite to those on spreading depression. Our findings demonstrate that spreading depression can occur as early as two days postnatally and that the characteristics of this phenomenon change with maturation. These results also indicate that 4-aminopyridine-induced spreading depression episodes and epileptiform activity are mediated by the activation of different types of excitatory amino acid receptors. Finally, spreading depression is influenced by blockade of the GABAA receptor.

4-Aminopyridine↗

PubMed1993

On the synchronous activity induced by 4-aminopyridine in the CA3 subfield of juvenile rat hippocampus.

1. Extracellular field potential and intracellular recordings were made in the CA3 subfield of hippocampal slices obtained from 10- to 24-day-old rats during perfusion with artificial cerebrospinal fluid (ACSF) containing the convulsant 4-aminopyridine (4-AP, 50 microM). 2. Three types of spontaneous, synchronous activity were recorded in the presence of 4-AP by employing extracellular microelectrodes positioned in the CA3 stratum (s.) radiatum: first, inter-ictal-like discharges that lasted 0.2-1.2 s and had an occurrence rate of 0.3-1.3 Hz; second, ictal-like events (duration: 3-40 s) that occurred at 4-38 x 10(-3) Hz; and third, large-amplitude (up to 8 mV) negative-going potentials that preceded the onset of the ictal-like events and thus appeared to initiate them. 3. None of these synchronous activities was consistently modified by addition of antagonists of the N-methyl-D-aspartate (NMDA) receptor to the ACSF. In contrast, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 2-10 microM) reversibly blocked interictal- and ictallike discharges. The only synchronous, spontaneous activity recorded in this type of medium consisted of the negative-going potentials that were abolished by the GABAA receptor antagonists bicuculline methiodide (5-20 microM) or picrotoxin (50 microM). Hence they were mediated through the activation of the GABAA receptor. 4. Profile analysis of the 4-AP-induced synchronous activity revealed that the gamma-aminobutyric acid (GABA)-mediated field potential had maximal negative amplitude in s. lacunosum-moleculare, attained equipotentiality at the border between s. radiatum and s. pyramidale, and became positive-going in s. oriens. These findings indicated that the GABA-mediated field potential presumably represented a depolarization occurring in the dendrites of CA3 pyramidal cells. 5. This conclusion was supported by intracellular analysis of the 4-AP-induced activity. The GABA-mediated potential was reflected by a depolarization of the membrane of CA3 pyramidal cells that triggered a few variable-amplitude, fractionated spikes or fast action potentials. By contrast, the ictal-like discharge was associated with a prolonged depolarization during which repetitive bursts of action potentials occurred. Short-lasting depolarizations with bursts of action potentials occurred during each interictal-like discharge. 6. The GABA-mediated potential recorded intracellularly in the presence of CNQX consisted of a prolonged depolarization (up to 12 s) that was still capable of triggering a few fast action potentials and/or fractionated spikes.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗

PubMed1992

CPP, an NMDA-receptor antagonist, blocks 4-aminopyridine-induced spreading depression episodes but not epileptiform activity in immature rat hippocampal slices.

Spontaneous episodes of spreading depression (SD) were observed in the CA3 subfield of immature or young (2-30 days postnatally) hippocampal slices perfused with medium containing 4-aminopyridine (4-AP, 50 microM). SD appeared in 34% of the hippocampal slices examined and was more frequently observed in slices obtained from 11 to 20-day-old animals. SD studied with extracellular field potential recordings consisted of large amplitude (18.7 +/- 1.1 mV, mean +/- S.E.M.) negative DC shifts that lasted 30-250 s. Unlike the epileptiform activity that was concomitantly seen during 4-AP application, SD was blocked by the NMDA receptor antagonist 3-((RS)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP, 2-10 microM). In contrast, 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX, 5 microM), a non-NMDA-type receptor antagonist, blocked the epileptiform activity but only increased the interval between SD episodes. These results demonstrate that immature hippocampal tissue is susceptible to SD episodes, when perfused with 4-AP-containing medium, and that the occurrence of these episodes presumably depends on the activation of the NMDA receptor. In addition these findings indicate that SD shows a sensitivity to excitatory amino acid receptor antagonists that differs from that of the epileptiform activity recorded simultaneously.

4-Aminopyridine↗

PubMed1991

Long-term increase in excitability induced by Mg(2+)-free medium in the absence of afferent stimulation in CA1 area of mouse hippocampal slices.

Omission of Mg ions from the perfusion fluid of hippocampal slices unblocks the N-methyl-D-aspartate (NMDA) type of glutamate receptor/channel, and induces long term enhancement of synaptic responses. In order to test the role of afferent activation in induction of long term potentiation in CA1 area by this process, we switched off stimulation during the time of perfusing the slices with Mg(2+)-free medium (30 min). In addition to a short lasting increase in synaptic activation we observed a long term increase in population spike amplitude in all slices tested (n = 5), which lasted for at least 2 h. This process was antagonized by 50-100 microM DL-2-amino-5-phosphonovalerate, a specific NMDA receptor antagonist (n = 8), but not by isolating CA1-CA3 areas prior to the testing (n = 5). These results suggest that the resting levels of the endogenous excitatory neurotransmitter(s) can induce long term increase in firing probability of CA1 pyramidal cells, when NMDA channels are unblocked, in the absence of afferent stimulation and irrespective of CA3 area prior excitation.

2-Amino-5-phosphonovalerate↗

PubMed1990

An electrophysiological study of the ontogenesis of adenosine receptors in the CA1 area of rat hippocampus.

The depressant effect of adenosine (Ad) was studied electrophysiologically in hippocampal slices from 5-, 10-, 15-, 20-, 30- and 120-day-old rats. Ad (10 microM) depressed the field EPSP in CA1 to the same extent in all age groups. Caffeine (Caf), an Ad receptor antagonist, enhanced and nitrobenzylthioinosine (NBI), an Ad uptake blocker, depressed the field EPSP. Both these effects were, however, less prominent in slices from younger animals, a finding consistent with lower extracellular levels of endogenous Ad in neonatal rats.

Action Potentials↗

PubMed1990

Long-term enhancement of postsynaptic excitability after brief exposure to Mg2(+)-free medium in normal and epileptic mice.

Brief exposure to Mg2(+)-free medium (MFM) enhanced the population response of CA1 neurons to stratum radiatum stimulation in hippocampal slices from normal (+/?) and epileptic tottering (tg/tg) mice. The enhancement was maintained in both groups for at least 2 h following reperfusion with normal medium (NM). Excitability curves obtained from the extracellular records suggest that, while both synaptic activation and postsynaptic excitability are enhanced during MFM perfusion, only the latter enhancement is maintained at significant levels after reperfusion with NM. The long-term increase in postsynaptic excitability was comparable in strength to that produced by long-term potentiation (LTP) inducing tetanic stimuli, was accompanied by an increase in the slope of the population spike/field excitatory postsynaptic potential (PS/fEPSP) curve and did not appear to depend on the induction of epileptiform activity by MFM. Both the short- and the long-term effects of MFM on synaptic activation and postsynaptic excitability were qualitatively similar in normal and epileptic mice and any quantitative differences were not statistically significant. Thus, epileptogenesis in the tottering mutant may not involve a change in the NMDA receptor-mediated control of excitability, at least in the CA1 area of hippocampus.

Action Potentials↗

PubMed1989

Action of anticonvulsants on hippocampal slices in Mg-free medium.

The effects of six prototype anticonvulsant drugs were investigated on epileptiform field potential discharges evoked in hippocampal slices of rats by removing magnesium ions from the perfusion fluid in order to reveal a possible interaction with N-methyl-D-aspartate (NMDA) receptor activation. All drugs reduced the multiple discharges with the following order of potency: midazolam greater than carbamazepine = phenytoin = phenobarbital greater than ethosuximide = valproate. They had a stronger depressant effect on the later population spikes but none of them abolished the epileptiform discharge. These effects can be explained by known mechanisms of action of the anticonvulsants tested and lend no support for a specific interaction with NMDA receptors.

Animals↗

PubMed1988

Membrane properties, response to amines and to tetanic stimulation of hippocampal neurons in the genetically epileptic mutant mouse tottering.

The petit-mal seizures of the "tottering" mutant mouse (tg) have been attributed to an exaggerated noradrenergic projection from locus coeruleus to the telencephalon (Noebels 1984). In order to investigate the possible epileptogenic mechanisms involved, we have compared hippocampal slices from epileptic (tg/tg) and phenotypically healthy (tg/+) mice. Resting potentials, action potentials and afterpotentials, membrane impedances and time constants were not significantly different in 11 neurons from each group. Bath application of noradrenaline, isoproterenol and histamine or a transient exposure to Mg++-free medium caused a long lasting increase in extracellularly recorded population spikes induced in CA1 by electrical stimulation of stratum radiatum. Isoproterenol blocked the calcium dependent afterhyperpolarization and accommodation of firing. Tetanization of afferent fibres evoked post-tetanic potentiation and long-term potentiation. All these results are qualitatively similar to those previously described in rats and guinea pigs and have revealed no significant difference between tg/tg and tg/+ mice.

Action Potentials↗

PubMed1987

Absence of modification in GABA and benzodiazepine binding and in choline acetyltransferase activity in brain areas of the epileptic mutant mouse tottering.

1. In the tottering mutant mouse, which suffers from epilepsy and cerebellar ataxia, we examined whether possible changes in GABA, benzodiazepine receptors and choline acetyltransferase (ChAT) activity are implicated in the pathophysiology of these animals. 2. No alteration in GABAA and GABAB binding could be detected in cerebellar membranes of epileptic mice as compared to normal mice. 3. Benzodiazepine receptor density and affinity showed no statistical difference in cerebellar membranes of epileptic and normal mice. 4. The activity of ChAT determined in the cortices of epileptic and normal mice did not differ significantly between the two groups.

Acetylcholine↗

PubMedDate not supplied

Increased postsynaptic excitability in hippocampal slices from the tottering epileptic mutant mouse.

The tottering mouse exhibits an inherited form of generalized epilepsy, which can be characterized by electroencephalographic, behavioral and pharmacological criteria as belonging to the 'absence' type. In vitro electrophysiological experiments in hippocampal slices revealed a higher than normal postsynaptic excitability in slices from epileptic mice. Upon stimulation of Schaffer collaterals, we obtained input/output curves from the CA1 pyramidal cell layer and determined several indices of synaptic activation and postsynaptic excitability. Only the latter were found to be statistically different: population spikes were elicited by relatively smaller field EPSPs (P less than 0.001) in the slices from epileptic mice. However, their maximum population spike was significantly smaller, which indicated that fewer neurons were available for firing. In the normal but not in the epileptic mice in vitro postsynaptic excitability was correlated to the age of the animal.

Action Potentials↗

PubMedDate not supplied

Comparison of the effects of increased potassium and of adenosine on hippocampal neurons from normal and genetically epileptic tg/tg mice.

Tottering mice are an experimental model of genetically determined generalized epilepsy of the absence type. We investigated possible mechanisms underlying epileptogenic hyperexcitability in these mice by studying input/output (I/O) curves of the extracellular response of CA1 neurons to stratum radiatum stimulation in hippocampal slices maintained in vitro. Increases in extracellular potassium are considered to contribute to epileptogenesis, whereas adenosine has been proposed to be an endogenous antiepileptic agent. Moderate elevations (+2 mM) of extracellular K+ concentrations induced a significantly smaller increase of this response (leftward shift of the input/output curves) in slices from epileptic mice as compared with controls. Perfusion of slices with adenosine 10 microM decreased excitability in both groups of slices, especially with regard to response threshold. Adenosine more effectively decreased the responses elicited by low-intensity stimulation than those elicited by high intensity. No significant difference between the groups of slices was observed. On the basis of the present data, it is unlikely that the previously observed hyperexcitability of hippocampal neurons of tottering mice results from a genetically altered sensitivity to moderate increases in [K+]o or to adenosine.

Adenosine↗

PubMedDate not supplied

Pentylenetetrazol-induced seizures decrease gamma-aminobutyric acid-mediated recurrent inhibition and enhance adenosine-mediated depression.

To elucidate the consequences of convulsions, we examined biochemically and electrophysiologically the brains of mice that had sustained two complete tonic-clonic convulsions after administration of pentylenetetrazol (PTZ 50 mg/kg intraperitoneally, i.p.), 48 and 24 h before decapitation. Control mice were injected with saline. Input/output curves of the extracellular synaptic responses in the CA1 area of hippocampal slices showed that PTZ-induced seizures do not establish the persistent change in hippocampal excitability itself that can be detected in vitro. However, use of the paired-pulse stimulation paradigm showed that gamma-aminobutyric acid A (GABAA)-mediated recurrent inhibition was significantly weaker (by 19-25%) in the CA1 area of slices from PTZ-treated mice (PTZ slices) as compared with slices from control mice (control slices). The density of GABAA receptors (high-affinity component) was also lower in hippocampus (by 19%) and cortex (by 14%) of PTZ-treated mice. A GABA-related disinhibitory mechanism underlying PTZ seizures may thus persist for 1 day after the seizure, predisposing the brain to subsequent seizures. On the other hand, the depressant effect of a single dose of adenosine 10 microM on the CA1 synaptic response was stronger (by 35% on population spikes) and longer lasting in PTZ slices as compared with controls. This could be attributed to significantly higher adenosine A1 receptor density in hippocampus (Bmax of [3H]CHA was higher by 34%) as well as cortex and cerebellum of these animals. The phenomenon may reflect an adenosine A1-mediated adaptive mechanism that offers protection from subsequent seizures.

Action Potentials↗