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Y Ben-Ari

Publications and source records attributed to Y Ben-Ari.

At least 253 records · Page 14Linked to original sources
PubMed1989

Hippocampal plasticity in childhood epilepsy.

Quantitative autoradiography was used to study changes in high affinity (Kd = 12 nM) binding sites for kainic acid, a marker of mossy fibers, in the hippocampus of childhood epileptics. We found a highly significant increase in the density of kainate binding sites in the CA3 region and in the fascia dentata in childhood epileptics as compared to age matched controls. We suggest that anatomical plasticity occurs in the hippocampus of human epileptics as in experimental models of epilepsy. The increase in kainate binding sites may contribute to the development of epileptic seizures.

Adolescent↗
PubMed1989

Calbindin-D 28K in hippocampal organotypic cultures.

Slices of hippocampus from 6-day-old rats were cultured for 2-4 weeks using the roller-tube technique. The organization of these explants was studied by immunocytochemical labeling of calbindin-D 28K (CaBP 28K). The development of the CaBP 28K staining was very close to that of the rat hippocampus in vivo with only 3 subpopulations of labeled cells: granule cells and their mossy fibers, pyramidal cells in the subiculum-CA1 zone and interneurons scattered in strata oriens and radiatum.

Animals↗
PubMed1989

Development of the cholinergic system in control and intra-uterine growth retarded rat brain.

The activity of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and muscarinic receptors was studied in control rats and in rats growth-retarded in utero because of reduction of the blood supply 5 days before birth. The different markers of the cholinergic system were estimated at P (postnatal day) 6, 9, 12, 15, 22 and 60 in cerebellum, hypothalamus, septum, striatum and CA1, CA3 and fascia dentata of the hippocampus. In control rats, there was a transient increase in ChAT activity in the septum during the second week of postnatal development. In the intrauterine growth retarded rats there was a marked delay in this developmental rise in CA1, CA3 at P6 and P9 and in the fascia dentata at P14 respectively. This delayed rise enzyme activity was associated with a significant reduction of muscarinic binding sites [( 3H]QNB) in the hippocampus. AChE staining showed a similar development in both groups. Therefore, the undernutrition produced by a reduction of the blood supply 5 days before birth is associated with a delayed maturation of cholinergic functions.

Acetylcholinesterase↗
PubMed1989

Transient increase of NMDA-binding sites in human hippocampus during development.

In the human hippocampus, the density of glutamate and N-methyl-D-aspartate (NMDA) binding sites follows during development a bell-shaped curve with a peak at 23-27 fetal weeks. We suggest that there is a transient increased density of NMDA binding sites during a restricted period of hippocampal development; this may play an important role in developmental plasticity.

Adult↗
PubMed1989

N-methyl-D-aspartate induces recurrent synchronized burst activity in immature hippocampal CA3 neurones in vitro.

Slices of hippocampus prepared from rats aged 1-10 days have been used to examine the chemosensitivity of CA3 pyramidal neurones to N-methyl-D-aspartate (NMDA). Superfusion of NMDA excited all neurones tested at all ages including the first day postnatal. In the majority of neurones this excitation was associated with the induction of a period of burst firing which disappeared on removal of NMDA. These bursts took the form of paroxysmal depolarizing shifts (PDSs) with a large amplitude depolarization and a high frequency discharge of spikes. The amplitude but not the frequency of occurrence of the PDSs was influenced by changes in the membrane potential and they could be abolished by either a high divalent cation medium or tetrodotoxin. Their occurrence was synchronous with an extracellularly recorded discharge. The NMDA induced excitation and the induction of the PDSs was attenuated by selective NMDA receptor antagonists D-aminophosphonovalerate (10-50 microM) and D,L-aminophosphonoheptanoate (20-30 microM). The results indicate that chemosensitivity to NMDA develops prenatally and that activation of NMDA receptors can in immature CA3 pyramidals induce recurrent synchronized burst activity.

2-Amino-5-phosphonovalerate↗
PubMed1989

Organization of the GABAergic system in the rat hippocampal formation: a quantitative immunocytochemical study.

Specific antibodies against gamma aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD) were used to study the organization of the GABAergic system in the rat hippocampal formation. Both the number of GABA-like-immunoreactive (Li) somata and neuropil density were assessed in semithin sections. Cell counts revealed that approximately 11% of the hippocampal neuronal population showed GABA-Li within the various planes of section. Each layer in the hippocampal formation had a characteristic organization of GABA-Li elements. In Ammon's horn, 80-95% of the neuronal somata within the apical and basal dendritic regions were GABA-Li positive. Within the pyramidal cell layer 5-8% of the cells were GABA-Li in the CA1 to CA3 subfields of Ammon's horn and only 3% were GABA-Li within that portion of the pyramidal cell layer that inserts into the hilus. Only slight differences in the density of the GABA-Li neuropil were observed within the CA1-CA3 dendritic regions. Restricted to the stratum lucidum was a dense band of GABA-Li label. Counts of immunoreactive grains localized on the perimeter of pyramidal (CA1-CA3) and granule somata revealed more terminal boutons on the CA3 cells than on CA1 and granule neuronal somata. A topographical distribution of GABA-Li somata and neuropil was found in the fascia dentata: There the label particularly concerned its suprapyramidal and rostrolateral portions. Approximately 40% of neurons in the molecular layer, 60% in the polymorph layer, and 18% within the hilar region were GABA-Li. Within the granule cell layer only 2% of the neurons were GABA-Li positive. Distinct differences in the density of the GABA-Li neuropil were present in the molecular, pericellular granular, and hilar regions of the fascia dentata. While the morphology of GABA-Li neuronal somata varied according to their hippocampal layer, the most heterogeneous cell types were found in the regio inferior of the hippocampus. There we have identified neurons that are reminiscent of the inferior region interneuron described in Golgi material by Amaral and Woodward (Brain Res. 124:225-236, '77). Moreover, particularly in the sagittal plane, we have identified oval, triangular, and round cells and that have processes oriented in a parallel arrangement, appearing to be aligned along the granule cell mossy fibers.

Animals↗
PubMed1989

Effects of colchicine treatment on the cholinergic septohippocampal system.

The influence of hippocampal target cells on the septohippocampal cholinergic system was studied using immunocytochemical and autoradiographic procedures. The destruction of dentate granular cells by colchicine injection promotes a significant increase in the density of acetylcholinesterase staining and cholinergic-muscarinic receptors in the zone denervated by the terminal axons of granular cells, which supports the hypothesis of a proliferation of cholinergic fibers in CA3. In the septal region the number of choline acetyl transferase positive cells was significantly lower (by 23%) ipsilaterally to the colchicine injection as compared to the contralateral side; when the hippocampus is almost completely destroyed by colchicine treatment this cell loss is more important (by over 50%). The present results agree with those of earlier studies and suggest that target-derived trophic factors are important for the maintenance of the basal forebrain cholinergic system and that the fascia dentata provides a significant source of such factors.

Acetylcholine↗
PubMed1989

Long-term potentiation in the hippocampus of the anaesthetized rat is not associated with a sustained enhanced release of endogenous excitatory amino acids.

The relationship between long-term potentiation of synaptic transmission and the release of endogenous glutamate and aspartate has been investigated in the CA1 region of the hippocampus and in the fascia dentata of the anaesthetized rat. A high-frequency train of electrical stimulation of afferent pathways produced a long lasting (greater than 2 h) enhancement of the field excitatory postsynaptic potential in CA1 and of the population spike in the fascia dentata. In both regions, this was not associated with a significant long lasting increase in the release of glutamate and aspartate. It is concluded that the maintenance of long-term potentiation is not associated with a sustained increase in the release of excitatory amino acids.

Anesthesia, General↗
PubMed1989

Endogenous and network bursts induced by N-methyl-D-aspartate and magnesium free medium in the CA3 region of the hippocampal slice.

The epileptogenic properties of N-methyl-D-aspartate and magnesium-free medium were investigated in the CA3 region of the hippocampal slice preparation in the rat. Bath application of N-methyl-D-aspartate (5-10 microM) or magnesium-free medium induced both spontaneous and stimulus-evoked bursts. Both endogenous and network bursts were generated, the former always preceding the latter. The paroxysmal depolarizing shift underlying the network bursts generated by N-methyl-D-aspartate and magnesium-free medium resembled a giant excitatory postsynaptic potential with a reversal potential near 0 mV and a synaptic input in the apical dendrites above the mossy fibre zone. In the presence of N-methyl-D-aspartate or magnesium-free medium, population bursts were synchronized by activating single CA3 neurons. N-methyl-D-aspartate receptor antagonists prevented the development of N-methyl-D-aspartate-induced spontaneous and stimulus-evoked bursts. However, the only N-methyl-D-aspartate receptor antagonist effective in preventing such bursts in magnesium-free medium was DL-3-[(+/-)-2-carboxypiperazin-4-yl-]-propyl-1-phosphonic acid. Endogenous bursting in the CA3 region has not been observed with other convulsants and thus may reflect the novel voltage dependence of the N-methyl-D-aspartate receptor gated ionic channel. N-methyl-D-aspartate receptors may also partially contribute to the excitatory interaction between CA3 neurons and thereby account for the synchronization of the population observed when activating single CA3 neurons.

Animals↗
PubMed1989

Hippocampal damage induced by ischemia and intra-amygdaloid kainate injection: effect on N-methyl-D-aspartate, N-(1-[2-thienyl]cyclohexyl)piperidine and glycine binding sites.

The N-methyl-D-aspartate receptor channel-complex is widely distributed in the hippocampus, particularly in the CA1 region, in the terminal field of CA3 pyramidal axons and in the fascia dentata, in the terminal field of the perforant pathway. In the present study, we have examined, in the rat, the effect of specific lesions of various neuronal populations of the hippocampus on the distribution of several markers of the N-methyl-D-aspartate receptor-channel complex. Anoxic-ischemic treatment produced a destruction of CA1 pyramidal cells (postsynaptic element): this was associated with a 50% loss of N-methyl-D-aspartate, glycine and N-(1-phenylcyclohexyl)piperidine binding sites. In contrast, the destruction of CA3 pyramidal cells and their axons (presynaptic element) by kainate treatment did not induce significant changes in the density of binding sites. The present results therefore strongly support an exclusively postsynaptic localization of the N-methyl-D-aspartate receptor-channel complex in CA1; the possibility of a localization of the remaining binding sites on glial cells or interneurons is discussed. In the molecular layer of the fascia dentata, the anoxic-ischemic treatment produced a partial destruction of the median perforant pathway (presynaptic element) associated with a decrease in the density of N-methyl-D-aspartate, N-(1-[2-thienyl]cyclohexyl)piperidine and glycine binding sites; this suggests that, in contrast to CA1, in the molecular layer of the fascia dentata, N-methyl-D-aspartate receptor-binding sites are located both pre- and postsynaptically.

Amygdala↗
PubMed1989

Giant synaptic potentials in immature rat CA3 hippocampal neurones.

1. Intracellular recordings were made from rat CA3 hippocampal neurones in vitro during the first eighteen days of postnatal life. The cells had resting membrane potentials more negative than -51 mV, action potentials greater than 55 mV and membrane input resistances of 117 +/- 12 M omega. An unusual characteristic of these cells was the presence of spontaneous giant depolarizing potentials (GDPs) which were observed during the first eight postnatal (P) days in over 85% of neurones. They were less frequent between P9 and P12 (48%) and disappeared after P12. 2. The GDPs were synchronously generated by a population of neurones; they reversed polarity at -27 mV when recorded with KCl-containing electrodes and at -51 mV with potassium acetate- or potassium methylsulphate-filled electrodes. 3. The GDPs were blocked by bath application of bicuculline (10 microM) or picrotoxin (100-200 microM). Exogenously applied gamma-aminobutyric acid (GABA; 0.2-1 mM) induced at resting membrane potential a bicuculline-sensitive membrane depolarization which reversed polarity at -25 and -51 mV when recorded with KCl- or potassium methylsulphate-filled electrodes respectively. 4. The GDPs were reduced in frequency or blocked by the N-methyl-D-aspartate (NMDA) receptor antagonists DL-2-amino-7-phosphonoheptanoate (AP-7; 50 microM), D(-)2-amino-5-phosphonovalerate (AP-5, 10-50 microM) and (+-)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 10-50 microM) or NMDA channel blockers phencyclidine (2 microM) and ketamine (20 microM). 5. Stimulation of the hilus during the first week of life evoked a GDP followed by a hyperpolarization. The GDPs were generated by a population of synchronized neurones and reversed polarity at -27 mV with KCl-filled electrodes and at -52 mV with potassium acetate- or potassium methylsulphate-containing electrodes. 6. Bath application of bicuculline (1-10 microM) or picrotoxin (100-200 microM) reversibly blocked the evoked GDPs in the majority of cells. The NMDA receptor antagonists AP-5 (50 microM), AP-7 (50 microM) and CPP (30 microM) usually reduced the amplitude and the duration of the evoked GDPs. In neurones in which evoked GDPs were blocked by bicuculline, a NMDA-mediated component was revealed by increasing the strength or the frequency of stimulation. 7. During the second week of postnatal life, when spontaneous GDPs were extremely rare or absent, superfusion with bicuculline (10 microM) induced, as in adult slices, interictal discharges. These reversed polarity near 0 mV with KCl- or potassium acetate-containing electrodes and were reduced in amplitude and duration by AP-5 (50 microM).(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1989

Anoxia produces smaller changes in synaptic transmission, membrane potential, and input resistance in immature rat hippocampus.

1. The reversible blocking effect of brief anoxia (2-4 min) on synaptic transmission was studied in submerged hippocampal slices (kept mostly at 34 degrees), obtained from adult (greater than 120 g) and very young (6-50 g) Wistar rats. Excitatory postsynaptic potentials (EPSPs) were recorded with extra- and intracellular electrodes, sometimes simultaneously: in CA1, they were evoked by stratum radiation stimulation, in CA3 by hilar stimulation. 2. In slices from adults, EPSPs in CA1 were depressed by 90% after 2 min of anoxia, and postanoxic recovery was relatively slow (one-half recovery times 4.0 +/- 0.23 min, mean +/- SE). EPSPs in CA3 were consistently more resistant, especially those generated by mossy fibers; after 2 min of anoxia, these were reduced by only 14.7 +/- 5.4%. 3. In newborn animals (PN1-4), both intra- and extracellular EPSPs (but no population spikes) could be recorded in CA1. Although smaller and more fatigable than in the adult, they were much more resistant to anoxia, after 2 min being reduced by only 44.1 +/- 8.8%; and they were not abolished even after 6-7 min. On the other hand, postanoxic recovery was very rapid, being one-half complete in 2.4 +/- 0.48 min. Only large and very prolonged (giant) depolarizing PSPs [probably inhibitory postsynaptic potentials (IPSPs)] could be recorded in CA3 neurons; they were rapidly blocked by anoxia. 4. In older pups (PN6-21), the CA1 EPSPs became progressively more sensitive to anoxia. At the end of the second week, they were as rapidly blocked as in slices from adults; but postanoxic recovery remained quicker throughout this period. In CA3, EPSPs could now be evoked that were as resistant to anoxia as in adult slices. 5. In both CA1 and CA3 neurons from adult rats, anoxia (for 2-3 min) reduced the input resistance (RN) by 45.7 +/- 6.25%. In CA1 neurons, there was most often some hyperpolarization (-7.2 +/- 1.8 mV), which was less consistent in CA3 cells. The return of O2 typically led to a second (postanoxic) phase of hyperpolarization (-7.9 +/- 1.93 mV). 6. At PN1-4, the resting potential (Vm) of most cells had to be maintained by current injection; the input resistance (RN) of CA1 neurons was 70% higher than in mature cells, and there was little time-dependent inward rectification. Anoxia produced no regular changes in Vm, and reductions in RN were very small (by only 9.6 +/- 5.0%). A postanoxic hyperpolarization was seen in only 2 neurons out of 11.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1989

Anoxia on slow inward currents of immature hippocampal neurons.

1. The effects of brief anoxia (2-4 min) on membrane currents--especially the tetrodotoxin (TTX)-insensitive, Cd2+-sensitive slow inward currents, presumed to be Ca2+ currents--were studied by single-electrode voltage clamp in CA1 and CA3 neurons in submerged hippocampal slices from adult and newborn Wistar rats (PN1-13). 2. In mature neurons, anoxia had no effect on Q-type inward relaxations, but slowly activating C-type outward currents were depressed. The most striking change was the suppression of Ca inward currents (especially the slowly inactivating L-type, by greater than 95%). This effect of anoxia was not sensitive to the N-methyl-D-aspartate (NMDA) receptor blocker, D-aminophosphonovalerate. Anoxia also reversibly abolished the NMDA-evoked inward current. 3. In neurons from newborn animals (PN1-6), Q-type inward relaxations and postanoxic outward currents were very small or undetectable. The slow inward (Ca) currents were smaller than in mature cells, but they showed a clearer separation between low-threshold, fast-inactivating and high-threshold, slowly inactivating currents. Both types of current were more resistant to anoxia (mean depression of L-type was by only 53.3 +/- 5.6%, mean +/- SE). 4. In such immature neurons, the NMDA-evoked inward currents were also more resistant to anoxia. 5. By PN7-13, increasing maturation was reflected in 1) larger voltage-dependent inward currents, 2) increasingly evident Q-type relaxations and postanoxic outward currents, and 3) near-complete blockade of inward currents by anoxia (at PN11-13, mean depression of L-type currents was by 98.5 +/- 1.5%).

Aging↗
PubMed1988

Antagonism of spontaneous and evoked bursts by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the CA3 region of the in vitro hippocampus.

Superfusion of hippocampal slices with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) antagonized kainate-induced bursts and bursts of unknown origin in the CA3 region. CNQX also increased the latency of and eventually blocked evoked bursts which persist following kainate washout. In contrast, D-(-)-2-amino-7-phosphonoheptanoic acid did not alter burst latency or block bursts unless applied subsequent to CNQX. We conclude that the quisqualate type receptor has a prominent role in burst generation with a smaller contribution from N-methyl-D-aspartate receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1988

Changes in voltage dependence of NMDA currents during development.

N-Methyl-D-aspartate (NMDA), applied by superfusion to hippocampal slices evokes comparable peak inward currents in CA3 pyramidal cells of adult and 0-10 day-old rats. However, NMDA current-voltage plots from immature neurones do not consistently show the region of negative slope conductance characteristic of adult. Therefore at a critical stage of development, NMDA activation may elicit substantial inward currents and Ca2+ influx at resting membrane potential.

Aging↗
PubMed1988

Transient increased density of NMDA binding sites in the developing rat hippocampus.

Using quantitative autoradiography and membrane preparations, the density of specific glutamate and N-methyl-D-aspartic acid (NMDA) binding sites have been determined in the developing rat hippocampus. We found an abrupt reduction in the density of NMDA binding sites after P8 (postnatal day) without change in affinity. The transient expression of NMDA receptors during maturation suggests that they may play a particularly important role in synaptogenesis.

Aging↗
PubMed1988

Blockade of excitatory synaptic transmission by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the hippocampus in vitro.

Superfusion of hippocampal slices with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 2-5 microM) reversibly blocked the Schaffer collateral and mossy fibre excitatory postsynaptic potential (EPSP), while sparing the fast and slow gamma-aminobutyric acid (GABA)-mediated inhibition. Membrane potential, input resistance and spike accommodation were not altered. Inward currents induced by quisqualate were reduced to a greater extent by CNQX than those induced by kainate or N-methyl-D-aspartate. We suggest that CNQX may be a useful antagonist to study excitatory amino acid-mediated synaptic transmission.

6-Cyano-7-nitroquinoxaline-2,3-dione↗