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Y Ben-Ari

Publications and source records attributed to Y Ben-Ari.

At least 217 records · Page 12Linked to original sources
PubMed1992

Effects of anoxia and aglycemia on the adult and immature hippocampus.

Brief anoxic episodes induce a loss of consciousness due to an interruption of synaptic responses and repeated on more sustained episodes induce a selective neuronal loss in vulnerable regions notably in the CA1-H1 region of the hippocampus. The use of brain slices kept in vitro has considerably improved our understanding of the mechanisms underlying anoxia and ischemia and the strategies of development of protective drugs or manipulations. This report reviews our present understanding of the effects of anoxia-ischemia on neuronal activity in particular concerning the abrupt and major changes in vulnerability which occur with maturation of the brain.

Aging↗
PubMed1992

Long-term potentiation and sprouting of mossy fibers produced by brief episodes of hyperactivity.

A brief application of high K+ or excitatory amino acids (i.e. kainic acid) generated repetitive synchronized burst that persisted for the duration of the application, in the CA3 field. Once excitability has been enhanced, further stimulation of various inputs evoked burst instead the typical excitatory postsynaptic potential--inhibitory postsynaptic potential sequence evoked in control conditions. These long-lasting changes in synaptic efficacy involved the activation of glutamate receptors of N-methyl-D-aspartate (NMDA) subtype. A brief period of hyperactivity (i.e. kindling of limbic pathways or administration of kainic acid) also resulted in a more delayed synaptic remodeling, notably of hippocampal mossy fibers (i.e. the axons of granule cells that mostly contact the apical dendrites of CA3 pyramidal neurons). Thus mossy fibers sprouted and made multiple ectopic asymmetrical synapses with spines of both granule cells dendrites and basilar dendrites of CA3 pyramidal cells. Finally, sprouting of mossy fibers was associated with a significant rise in the density of kainic acid binding sites (fmol/mg tissue) in the aberrantly innervated zones: the inner third of molecular layer and the stratum oriens of CA3. Saturation studies revealed that this rise did not significantly affect the affinity (Kd values) but the Bmax. In conclusion, brief seizure episodes produced in the hippocampus remarkably long-lasting changes in synaptic efficacy; synaptic density and the mean density of excitatory amino acid receptors of non-NMDA subtype. The role that such plastic changes may play in the permanence of the epilepsy is finally discussed.

Afferent Pathways↗
PubMed1991

Rapid activation of hippocampal casein kinase II during long-term potentiation.

Several studies suggest that protein kinase C and type II Ca2+/calmodulin-dependent protein kinase are activated during induction of long-term potentiation (LTP). We now report that casein kinase II (CK-II), which is present in high concentration in the hippocampus, is also activated in the CA1 region during LTP. CK-II activity increased within 2 min after a train of high-frequency electrical stimulations and reached a maximum (2-fold increase) 5 min later before returning to baseline value. The stimulated protein kinase activity, which was blocked by a selective antagonist of N-methyl-D-aspartate receptors, exhibited specific properties of CK-II, including phosphorylation of the specific substrates of CK-II, marked inhibition by a low heparin concentration, and the use of GTP as a phosphate donor. CK-II activity was also selectively and rapidly augmented in another form of LTP produced by bath application of tetraethylammonium; this LTP (called LTPk) is Ca2+ dependent but N-methyl-D-aspartate independent. Phosphorylation of casein that was not inhibited by heparin (i.e., casein kinase I) remained unchanged. We suggest that an increase in CK-II activity is important in LTP induction.

Adenosine Triphosphate↗
PubMed1991

Benzodiazepines do not potentiate GABA responses in neonatal hippocampal neurons.

Benzodiazepines (midazolam; flunitrazepam) and pentobarbital increase the response to exogenous gamma-aminobutyric acid (GABA) in adult hippocampal cells. We report in this paper that in contrast pentobarbital but not benzodiazepine potentiate the effects of exogenous (GABA) in neurons recorded from slices of less than two weeks old. This finding suggests that the functional association of benzodiazepine and GABAA receptors is changed during early postnatal life.

Animals↗
PubMed1991

Autoradiographic study of the cellular localization of [3H]glibenclamide binding sites in the rat hippocampus.

[3H]Glibenclamide, a potent ATP-sensitive K+ channel blocker, is a specific ligand for the identification of the sulfonylureas receptors which are closely related to ATP-sensitive K+ channels. In order to determine the pre- or postsynaptic localization of these receptors in the rat hippocampus, we studied the effects of selective kainate or colchicine-induced lesions on the regional distribution of [3H]glibenclamide binding. A decreased binding was found in the following conditions: in CA3, after destruction of the mossy fiber terminals but not of the CA3 cells; in CA1, after destruction of the CA1 cells but not of the Schaffer collaterals; in the fascia dentata, after destruction of the granule cells. These results suggest that glibenclamide binding sites are mainly localized on the mossy fibers in CA3, and on the granular and pyramidal neurons in the fascia dentata and CA1, respectively.

Animals↗
PubMed1991

Two binding sites for [3H]glibenclamide in the rat brain.

The binding of [3H]glibenclamide, a potent sulfonylurea which blocks ATP-sensitive potassium channels, was studied in the rat brain. A Scatchard plot of saturation isotherms suggests that [3H]glibenclamide binds in various brain regions to a high- and a low-affinity binding site (Kd values of 0.21 nM and 111 nM and Bmax values of 41 and 1060 fmol/mg protein, respectively). Competitive binding assays with various unlabelled sulfonylureas showed biphasic displacements of [3H]glibenclamide with pseudo-Hill coefficients significantly different from unity. These data indicate the existence of a heterogeneity of binding sites to [3H]glibenclamide in the rat brain; this may correlate with the variability of effects of sulfonylureas observed from physiological experiments.

Animals↗
PubMed1991

Novel form of long-term potentiation produced by a K+ channel blocker in the hippocampus.

Long-term potentiation (LTP) of synaptic transmission in the hippocampus is a widely studied model of memory processes. In the CA1 region, LTP is triggered by the entry of Ca2+ through N-methyl-D-aspartate (NMDA) receptor channels and maintained by the activation of Ca2(+)-sensitive intracellular messengers. We now report that in CA1, a transient block by tetraethylammonium of IC, IM and the delayed rectifier (IK) produces a Ca2(+)-dependent NMDA-independent form of LTP. Our results suggest that this new form of LTP (referred as to LTPK) is induced by a transient enhanced release of glutamate which generates a depolarization by way of the non-NMDA receptors and the consequent activation of voltage-dependent Ca2+ channels.

Animals↗
PubMed1991

GABA: an excitatory transmitter in early postnatal life.

In the adult mammalian CNS, GABA is the main inhibitory transmitter. It inhibits neuronal firing by increasing a Cl- conductance. Bicuculline blocks this effect and induces interictal discharges. A different picture is present in neonatal hippocampal neurones, where synaptically released or exogenously applied GABA depolarizes and excites neuronal membranes--an effect that is due to a different Cl- gradient. In fact, during the early neonatal period, GABA acting on GABAA receptors provides most of the excitatory drive, whereas excitatory glutamatergic synapses are quiescent. It is suggested that during development GABA exerts mainly a trophic action through membrane depolarization and a rise in intracellular Ca2+.

Animals↗
PubMed1991

Transient cerebral ischemia induces changes in SRIF mRNA in the fascia dentata.

A transient cerebral ischemia produced in rats by 4-vessel occlusion, produces with a delay of 24 h a fall in the number of somatostatin-containing neurons. In the present study we show that this loss is preceded by a loss of somatostatin mRNA that starts as soon as 30 min after the anoxic episode. By 24 h of revascularization the surviving somatostatinergic hilar cells present a transient recovery of hybridization signal. This effect could be related to a previously reported increase in intracellular calcium.

Animals↗
PubMed1991

Effects of neonatal gamma-ray irradiation on rat hippocampus--I. Postnatal maturation of hippocampal cells.

The axons of dentate granule cells, the mossy fibres, establish synaptic contacts with the thorny excrescences of the apical dendrite of CA3 pyramidal neurons. Dentate granule granule cells develop postnatally in rats, whereas the CA3 pyramidal cells are generated before birth. In the present studies, using unilateral neonatal gamma-ray irradiation to destroy the granule cells in one hemisphere, we have studied the effect of mossy fibre deprivation on the development of their targets. We show that such "degranulation" prevents the normal development of giant thorny excrescences, suggesting that the development of thorny excrescences in CA3 pyramidal neurons is under the control of mossy fibres. In contrast, irradiation of the hippocampus of the neonatal rat does not affect the development of the dendritic arborization of CA3 pyramidal cells and their non-mossy dendritic spines.

Animals↗
PubMed1991

Effects of neonatal gamma-ray irradiation on rat hippocampus--II. Development of excitatory amino acid binding sites.

In the rat, neonatal irradiation produces a destruction of dentate granule cells and prevents the development of the mossy fibre-CA3 pyramidal cell synapse. The developmental increase of high affinity kainate binding sites in the stratum lucidum was reduced on the irradiated side as compared with the control side. This suggests that a proportion of high affinity kainate binding sites is associated with mossy fibres. In contrast, the developmental profile of N-methyl-D-aspartate binding sites, which are associated with associational and commissural synapses in CA3, was not affected by irradiation. The role that afferent fibres may play in the development of pyramidal cells is discussed in connection with the modulatory effects of glutamate receptors on the development of neurons.

Animals↗
PubMed1991

Persistent pulsatile release of glutamate induced by N-methyl-D-aspartate in neonatal rat hippocampal neurones.

1. Intracellular recordings were made from CA3 hippocampal neurones in vitro, during the first ten days of postnatal life and in adulthood. 2. Repeated (three to six) applications of N-methyl-D-aspartate (NMDA), in the presence of tetrodotoxin (TTX, 1-3 microM) and K+ channel blockers (tetraethylammonium chloride or bromide (TEA), 10 mM, and Cs+, 2 mM; or 4-aminopyridine (4-AP), 30-50 microM, and Cs+, 2 mM) induced in neonatal but not in adult neurones, periodic inward currents (PICs) which persisted for several hours after the last application of NMDA. 3. PICs which were due to non-specific cation currents had a frequency of 0.10 +/- 0.04 Hz, and an amplitude of 1.1 +/- 0.28 nA at holding potentials between -40 and -50 mV. The amplitude was a linear function of the membrane potential over the range -70 to +20 mV. They reversed polarity at 4.1 +/- 9.8 mV. 4. K+ channel blockers alone failed to induce PICs. Repeated (three to six) brief applications of high (12 mM) K+ medium also induced PICs. The frequency and amplitude of K(+)-induced PICs were however considerably reduced by concomitant applications of the NMDA receptor antagonist D,L-3-[( +/- )-2-carboxypiperazin-4-yl-]propyl-1-phosphonic acid (CPP, 20 microM). PICs could be induced also by caffeine (1 mM) in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX, 200 microM), TTX, TEA and Cs+. 5. Intracellular injection of the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) did not prevent the induction of PICs by NMDA. However PICs were blocked by removal of the external calcium and by the calcium antagonists cobalt (2 mM) and cadmium (50 microM). 6. In spite of blockade of propagated synaptic activity by TTX, PICs were synchronous in a pair of intracellularly recorded cells. They were also synchronous with extracellular spikes recorded by electrodes located into stratum pyramidal or stratum radiatum. 7. Once established, PICs were unaffected by NMDA receptor antagonists D(-)2-amino-5-phosphonovaleric acid (AP-5, 50 microM), CPP (20 microM) and the NMDA channel blocker ketamine (10 microM). They were reversibly blocked by the broad spectrum excitatory amino acid antagonist kynurenic acid (1 mM) and by the selective non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). 8. It is concluded that PICs are generated in neonatal neurones by a synchronous, pulsatile release of glutamate from presynaptic nerve terminals, secondary to oscillations in intracellular calcium.

Action Potentials↗
PubMed1991

Characterization of sulfonylurea receptors and the action of potassium channel openers on cholinergic neurotransmission in guinea pig isolated small intestine.

Specific binding sites for [3H]glibenclamide, a potent ATP-sensitive K+ channel blocker, have been characterized in the isolated guinea pig longitudinal muscle-myenteric plexus preparation. The Scatchard plot of the saturation isotherm was curvilinear and revealed two binding sites, one of high affinity (Kd = 0.42 nM; maximum binding site = 156 fmol/mg of protein), the other of low affinity (Kd = 83 nM; maximum binding site = 3100 fmol/mg of protein). Displacement experiments in the presence of various sulfonylureas showed the same order of potency for the two binding sites (glibenclamide greater than gliquidone greater than glipizide glibornuride greater than chlorpropamide greater than tolbutamide). The K+ channel opener RP 49356 (but not diazoxide or cromakalim) displaced the [3H] glibenclamide with an IC50 of 4.8 microM. The effects of the K+ channel openers diazoxide, RP 49356, cromakalim and its two optical isomers BRL 38226 and BRL 38227 were also studied on the electrically induced contractions of isolated guinea pig small intestine. These compounds produce an inhibition of neurally evoked twitch height with pD2 values of 4.5 to 6.2 (BRL 38227 greater than cromakalim greater than RP 49356 greater than diazoxide, whereas BRL 38226 was practically ineffective). The effects of cromakalim and RP 49356 were antagonized competitively by glibenclamide (pA2 = 7.2) and other sulfonylureas, suggesting they act on ATP-sensitive K+ channels. Affinities of the sulfonylureas obtained from concentration-response curves to cromakalim on electrically induced contractions are better correlated with the IC50 value corresponding to the low affinity binding site than to the high affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP-Binding Cassette Transporters↗
PubMed1990

Effects of kainic acid-induced seizures and ischemia on c-fos-like proteins in rat brain.

We have analyzed the brain pattern and time-course of c-fos-like proteins expression in kainic acid-induced seizures in the rat. C-fos-like immunoreactivity increased initially in the hippocampus, notably in the dentate gyrus, at the time of the first limbic motor seizure (90 min after kainate). C-fos-like labelling progressively involved different structures of the limbic system when the rats manifested a permanent epileptic state (3-6 h). The labelling was still conspicuous 12 h after kainate treatment and progressively declined to reach control levels 48 h after kainate. This time-course is similar to that produced by kainic acid on 2-deoxyglucose consumption and correlates with the electrographic changes previously described, supporting the idea that c-fos-like immunostaining may provide a useful marker of neuronal activity, with a cellular resolution. Since anoxic-ischemic treatment produces a very slight and transient increase in c-fos-like immunostaining restricted to the fascia dentata, c-fos-like expression is seizure-related and not due to a local hypoxia or ischemia.

Amino Acid Sequence↗
PubMed1990

Developmental study of [3H]TCP and [3H]glycine binding sites in the rat hippocampus.

The postnatal development of [3H]thienylphencyclidine ([3H]TCP) sites in rat hippocampus has been studied autoradiographically and with membrane preparations. [3H]TCP binding increased progressively from birth to adulthood; this is due to a change in the maximal number of sites (Bmax) but not in the affinity (Kd). A different developmental pattern was found for strychnine-insensitive [3H]glycine binding which also increased after birth, but reached adult levels earlier than [3H]TCP binding. The ontogenesis of TCP or glycine sites also differed from that previously described for N-methyl-D-aspartate (NMDA) sites in the hippocampus. In neonatal, as in adult hippocampus, [3H]TCP binding was enhanced by NMDA or glycine and reduced by Mg2+. We suggest that TCP sites are functionally coupled to the NMDA receptor-ion channel complex in developing as in mature hippocampus, but that there are developmental changes in the receptor channel complex.

Aging↗