D-aminophosphonovaleric acid-sensitive spontaneous giant EPSPs in immature rat hippocampal neurones.
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2-Amino-5-phosphonovalerate↗
Biomedical subjects
Y Ben-Ari
Publications and source records attributed to Y Ben-Ari.
Release of proteins during long-term potentiation in the hippocampus of the anaesthetized rat.
Using a push-pull device, the release of endogenous proteins in the extracellular space was investigated in the CA1 region of the hippocampus of anaesthetized rats. With low-frequency stimulation of the Schaffer collaterals, there was a relatively stable release of 5 proteins (64, 54, 48, 45 and 16 kDa). A train of high-frequency stimulation produced a long-lasting enhancement of the negative field EPSP and a delayed (90-120 min) enhancement of the release of these proteins. An additional 19 kDa protein was present only 90 min after the train. These observations raise the possibility that release of proteins might be involved in the maintenance of LTP.
2-Amino-5-phosphonovalerate↗
Epileptiform bursts elicited in CA3 hippocampal neurons by a variety of convulsants are not blocked by N-methyl-D-aspartate antagonists.
Intracellular and extracellular recordings from CA3 hippocampal neurons in vitro were used to study the ability of several NMDA (N-methyl-D-aspartate) receptor antagonists to suppress epileptiform bursts induced by NMDA and convulsants not thought to act at NMDA receptors. The antagonists, APV (D-2-amino-5-phosphonovalerate), AP-7 (D,L-2-amino-7-phosphonohepatanoate) and CPP (D,L-3[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid), blocked the spontaneous and evoked bursts induced by NMDA. CPP, but not APV or AP-7, prevented the development of bursts induced by Mg-free medium. The NMDA antagonists failed to block bursting induced by kainate, 7 mM K+, mast cell degranulating peptide, anoxia or spontaneous bursting. In some cases the NMDA antagonists induced spontaneous bursts or enhanced burst frequency, a proconvulsant effect. It is concluded that activation of NMDA receptors is sufficient but not necessary for burst generation in the CA3 region.
2-Amino-5-phosphonovalerate↗
Is senile dementia of the Alzheimer type associated with hippocampal plasticity?
The density of binding sites for excitatory amino acids in the hippocampus of SDAT (senile dementia of the Alzheimer type) patients has been investigated. This was compared to that found in younger and old non-dement cases. In the SDAT hippocampi there was a significant decrease in the glutamate and kainate binding. This reduction correlated positively with the degree of the severity of neurological and pathological disease. In spite of an extensive denervation of SDAT hippocampi, there was no sign of sprouting of mossy fibers; this observation indicates a loss of plasticity in the hippocampus of SDAT patients.
Adult↗
Brief anoxic episodes induce long-lasting changes in synaptic properties of rat CA3 hippocampal neurons.
The effects of brief anoxic episodes on rat CA3 hippocampal neurons were studied with intracellular and extracellular techniques in the in vitro slice preparation. After repeated (3-7 times), brief (2-6 min duration each) applications of artificial cerebrospinal fluid (ACSF) saturated with 95% N2 and 5% CO2, electrical stimulation of various inputs to CA3 neurons, evoked an excitatory postsynaptic potential (EPSP) followed by an all-or-none burst. This response which persisted for several hours after the last anoxic episode, is reminiscent of the bursts induced by various convulsive agents. Post anoxic bursts are generated by a polysynaptic network which converge on the apical distal segment of CA3 neurons. It is concluded that a repetitive impairement of metabolism produces long lasting changes in the synaptic properties of CA3 neurons.
Action Potentials↗
Effect of ischemia and intra-amygdaloid kainate injection on the density of NMDA binding sites in the hippocampal CA1 region.
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Amygdala↗
Long-lasting modification of the synaptic properties of rat CA3 hippocampal neurones induced by kainic acid.
1. The action of a short bath application of kainic acid (KA, 200-250 nM, 3-5 min) on the CA3 region of rat hippocampal slices has been studied with intracellular and extracellular recording techniques. 2. KA evoked bursts which persisted for 10-15 min. In addition, after KA, electrical stimulation of various inputs to CA3 which elicited an EPSP-IPSP sequence in control conditions evoked an EPSP followed by a burst. This evoked response persisted for several hours after removal of KA suggesting the occurrence of a long-lasting modification of the synaptic properties of CA3 neurones. 3. Intracellular recordings showed the spontaneous and evoked bursts to consist of five to ten action potentials riding on a depolarizing shift 10-25 mV in amplitude and 40-100 ms in duration. Both spontaneous and evoked bursts were followed by a long-lasting hyperpolarization 15-25 mV in amplitude and 1-1.5 s in duration. 4. We propose that both spontaneous and evoked synchronized bursts are generated by a polysynaptic network since: (a) intracellularly recorded bursts were synchronized with the bursts in extracellular field recording; (b) bursts disappeared when synaptic transmission or Na+ action potential were blocked by cobalt (1 mM) or TTX (1 microM) respectively; (c) bursts were suppressed by elevated divalent cation concentration; (d) burst occurrence was independent of the membrane potential of the cell; (e) the depolarization shift that underlies the bursts was a linear function of the membrane potential and reversed in polarity at 0 mV. In addition, the evoked bursts were all-or-none events with a variable latency. 5. Laminar profile analysis of the spontaneous and evoked bursts suggests that they were generated by synapses located on the distal apical segments of the dendrites of CA3 pyramidal cells. 7. The persistence of the evoked bursts was neither due to a persistent change in cell excitability nor to a long-lasting reduction in GABAergic synaptic inhibition. 8. Bath application of a high concentration of potassium (7 mM) also induced spontaneous and evoked bursts; the latter also persisted several hours after return to control medium. 9. The N-methyl-D-aspartate (NMDA) antagonist, D-APV (D(-)-2-amino-5-phosphonovaleric acid) (30 microM), did not block the spontaneous discharges induced by KA or high potassium, but prevented the long-lasting effects on the synaptic responses.(ABSTRACT TRUNCATED AT 400 WORDS)
2-Amino-5-phosphonovalerate↗
[Is Alzheimer's senile dementia associated with the phenomena of reactive synaptogenesis in the hippocampus?].
The densities of specific binding sites for glutamate or its analogue kainate were determined in the hippocampi of patients having suffered of senile dementia of the Alzheimer type (SDAT) and compared to age matched controls. The densities of sites were reduced in SDAT cases. These results indicate a lack of hippocampal plasticity in senile dementia of Alzheimer type.
Adult↗
Distribution of GABA-like immunoreactivity in the rat amygdaloid complex.
The distribution of GABA-like (GABA-Li) immunoreactivity in the rat amygdaloid complex was studied by using an anti-GABA antibody. GABA-Li positive neurons and processes were present in every nucleus of the complex. Three patterns of immunoreactivity were revealed: (1) the intercalated masses and the lateral olfactory tract nucleus exhibited the most intense staining of the neuropil, and virtually every neuron was labeled, (2) the central and medial nuclei contained intensely labeled neuropil and moderately labeled neurons, and (3) in the remaining nuclei, the neuropil was weakly labeled, and relatively numerous GABA-Li neurons were present. Our results suggest that: (1) the intercalated masses and lateral olfactory tract nucleus consist of large aggregates of GABA-Li immunoreactive neurons, and (2) the lateral, basal dorsal, and the posterior cortical nuclei may constitute a significant source of GABAergic connections to other amygdaloid nuclei, in particular to the medial and central nuclei.
Amygdala↗
Long-lasting potentiation produced by a phorbol ester in the hippocampus of the anaesthetized rat is not associated with a persistent enhanced release of excitatory amino acids.
The relationship between the long-lasting enhancement of synaptic transmission produced by a phorbol ester and the release of endogenous excitatory amino acids has been investigated in the CA1 hippocampal region of the anaesthetized rat. Using the push-pull technique, the concentration of glutamate and aspartate was assayed in the perfusate by high-pressure liquid chromatography. Application of phorbol 12-13 diacetate produced a long lasting enhancement of the field excitatory postsynaptic potential (EPSP) (over 2 h). This was associated with a brief (10 min) significant increase in the release of glutamate and aspartate. However, subsequently the levels of the amino acids in the perfusate were not different from the pre-drug (control) levels although the field EPSP was still enhanced. It is concluded that the long-lasting enhancement produced by phorbol ester is not due to a persistent increase in the release of excitatory amino acids.
Action Potentials↗
Aberrant growth of mossy fibers and enhanced kainic acid binding sites induced in rats by early hyperthyroidism.
Early hyperthyroidism induces an aberrant growth of hippocampal mossy fibers both in the fascia dentata (supragranular layer) and in Ammon's horn (infrapyramidal layer of CA3). Using a quantitative autoradiographic method, we found a corresponding increase in kainic acid binding sites supporting previous observations of a very close association between mossy fiber terminals and kainic acid binding sites.
Animals↗
Is activation of N-methyl-D-aspartate receptor gated channels sufficient to induce long term potentiation?
Superfusion of hippocampal slices with Mg2+ free medium (20-30 min) produced in CA1 interictal bursts and an enhancement of the Schaffer collateral synaptic response which persisted for over 2 h after return to control media. This long lasting effect, which was blocked by N-methyl-D-aspartate (NMDA) antagonists, was not associated with changes in postsynaptic cell excitability. A cut between CA3 and CA1, which blocked the bursts in CA1 (but not in CA3), also abolished the long lasting effects of Mg2+ free medium. It is concluded that the activation of NMDA receptors gated ionic channels is insufficient per se to induce a long term potentiation of synaptic transmission.
Action Potentials↗
Selective release of endogenous zinc from the hippocampal mossy fibers in situ.
The release of endogenous zinc was studied in the hippocampus of the anesthetized rat. Push-pull cannulae were bilaterally introduced in the hippocampus and zinc concentrations determined by atomic absorption spectrophotometry. We first studied the regional distribution of K+-evoked release of zinc. A 2 min (30 mM) K+ pulse produced a release of endogenous zinc, when the push-pull cannulae were located in the vicinity of the mossy fibers (CA3 or hilus) but not in other regions (including CA1, fimbria, molecular layer of the fascia dentata, thalamus etc...). In CA3 the maximal release was of 2000 ng/ml (200 times the levels of zinc present in the cerebrospinal fluid (CSF)). Destruction of the mossy fibers by a local unilateral injection of 1.5 micrograms of colchicine dissolved in 0.6 microliter of a saline solution, eliminated this release without affecting the release in the control (contralateral) side. Electrical stimulation of the perforant path at 1 Hz did not evoke a release of zinc. In contrast at 10 Hz this stimulation produced a burst of population spike and a significant release of zinc in the mossy fibers (and not in other regions of the hippocampus). These experiments provide direct evidence that zinc is selectively released from the mossy fibers.
Animals↗
Kainate binding sites in the hippocampal mossy fibers: localization and plasticity.
The regional distribution of high affinity binding sites for kainic acid has been determined in rat hippocampi by quantitative autoradiography. Selective lesions were made in order to determine the exact localization of these sites in the mossy fiber system, and to evaluate whether the sprouting and synaptic reorganization of the mossy fibers are associated with alterations in the distribution of these binding sites. The results show that kainate binding sites in the stratum lucidum are more vulnerable to destruction of the granules and their mossy fibers by intrahippocampal colchicine injections than to destruction of the CA3/CA4 pyramidal cells by injection of kainate into the amygdala. This suggests that a substantial proportion of the kainate binding sites is associated with the mossy fiber terminals (i.e. the presynaptic elements). Furthermore, in keeping with an earlier study, destruction of the pyramidal neurons of CA3 by intracerebral kainate produced a dark Timm positive band in the supragranular zone which is due to the sprouting of mossy fibers. This was associated with an increase in the density of kainate binding sites, which further stresses the parallelism between the distribution of these sites and mossy fiber terminals.
Animals↗
Gabaergic neurons of the hippocampus: development in homotopic grafts and in dissociated cell cultures.
The hippocampus taken from E18-E19 rat embryos was dissociated into a cell suspension and was either grafted into the hippocampus of adult rats or cultured. The growth of GABAergic neurons was examined using a GABA directed antiserum. The implanted tissue was capable of survival and growth without exhibiting a laminar organization. Most of the various morphological neuronal types could be observed, establishing different types of synapses; however, granule neurons were rarely encountered. A substantial proportion of GABA-positive neurons was detected within the graft with profuse labelling of the neuropil. In cultures issued from the same cell suspension, GABA-immunoreactive neurons were numerous and had different morphologies. Altogether these data suggest that GABA neurons express a high potential for growth and sprouting in vitro and in vivo.
Animals↗
Brain damage caused by seizure activity.
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Animals↗
Subconjunctival hemorrhage in pertussis.
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Child↗
Kainate reduces two voltage-dependent potassium conductances in rat hippocampal neurons in vitro.
The mechanisms of action of kainate were studied in CA1 hippocampal neurons using the single electrode voltage-clamp technique in vitro. Kainate (100-200 nM) reduced the potassium current which is responsible for the anomalous rectification (IQ). In 30% of the cells the drug reduced the calcium-dependent potassium current (IC) which is responsible for the afterhyperpolarization that follows calcium action potentials. The reduction of IC will contribute to the enhancement of the neural excitability by this drug.
Action Potentials↗