Showing papers on "Long-term potentiation published in 1987"
TL;DR: A simple neuronal model capable of superimposing multiple memory traces within the same matrix of connections is outlined, and the correspondence between such models and the properties of LTE in the context of the hippocampal circuitry in which it occurs is considered.
1,254 citations
TL;DR: The recent evidence that has revealed the pivotal role of NMDA receptors in the induction of LTP is described, and the possible mechanisms involved in the maintenance of the potentiated state are discussed.
1,153 citations
TL;DR: The available evidence suggests that L TP does occur in conjunction with behavioral learning-although whether it is necessary and sufficient is far from certain.
Abstract: History and Definition In 1973, two reports appeared in the Journal of Physiology that described a long-term potentiation (L TP) of synaptic transmission at a monosynaptic junction in the mammalian eNS. These two papers, one dealing with the anesthetized rabbit preparation (Bliss & L0mo 1973) and the other dealing with the unanesthetized rabbit (Bliss & Gardner-Medwin 1973), were of considerable interest because they marked the first demonstration of a neurophysiological alteration in the mammalian brain possessing a con siderable time-course. Prior to these observations, neurophysiological phenomena were known to be of relatively modest temporal extent. The experiments of Bliss and colleagues showed that in the perforant path to dentate gyrus synapse, substantial increases in synaptic efficacy were observed following tetanic stimulation of afferent fibers. Synaptic efficacy refers to the postsynapti c response to a constant afferent volley. The changes (on the order of a 50% increase in the amplitude of the response) lasted for at least ten hours in the anesthetized preparation and up to 16 weeks in the unanesthetized preparation following a series of tetanic stimuli . These results attracted great interest because of the possi bility that the phenomenon might underlie some aspects of memory storage. A critical question-not yet completely answered-was stated by Bliss & Lemo : "Whether or not the intact animal makes use in real life of a property which has been revealed by synchronous, repetitive volleys to a population of fibers the normal and pattern of activity along which are unknown, is another matter" (Bliss & L0mo 1973, p. 355). As we shall see, the available evidence suggests that L TP does occur in conjunction with behavioral learning-although whether it is necessary and sufficient is far from certain.
1,081 citations
TL;DR: In this article, the authors used intracellular recording techniques to show that LTP can be induced by high frequency stimulation of the optic radiation in slices of the visual cortex of adult rats.
Abstract: In the hippocampus, which is phylogenetically older than the cerebral neocortex, high frequency stimulation of afferent pathways leads to long-term potentiation (LTP) of synaptic transmission1–5. This use-dependent malleability is of considerable interest because it may serve as a substrate for memory processes. However, in the neocortex, whose involvement in learning is undisputed, attempts to demonstrate LTP have remained inconclusive6–8. Here we use intracellular recording techniques to show that LTP can be induced by high frequency stimulation of the optic radiation in slices of the visual cortex of adult rats. We identify as a necessary prerequisite for the induction of LTP the activation of the membrane channel that is associated with the NMDA (N-methyl-D-aspartate) receptor. Selective blockade of this receptor system with DL-2-amino-5-phosphonovalerate consistently prevents LTP as in most hippocampal pathways9–11. In most cortical neurons the activation of the NMDA mechanism and hence the induction of LTP in these experiments requires a concomitant reduction of GABAergic inhibition by low doses of the GABAA antagonist bicuculline. This indicates that in the neocortex the activation threshold of the NMDA-mechanism and consequently the susceptibility to LTP, are strongly influenced by inhibitory processes.
814 citations
TL;DR: Four or more distinct single-channel currents are evoked by applying glutamate to each outside-out membrane patch, which are compatible with the model that all the single channel conductances activated by glutamate reflect the operation of one or two complex molecular entities.
Abstract: There is considerable evidence that glutamate is the principal neurotransmitter that mediates fast excitatory synaptic transmission in the vertebrate central nervous system1–3. This single transmitter seems to activate two or three distinct types of receptors, defined by their affinities for three selective structural analogues of glutamate, NMDA (N-methyl-D-aspartate), quisqualate and kainate1–6. All these agonists increase membrane permeability to monovalent cations7–9, but NMDA also activates a conductance that permits significant calcium influx10,11 and is blocked in a voltage-dependent manner by extracellular magnesium12,13. Fast synaptic excitation seems to be mediated mainly by kainate/quisqualate receptors14–18, although NMDA receptors are sometimes activated 19–21. We have investigated the properties of these conductances using single-channel recording22 in primary cultures of hippocampal neurons, because the hippocampus contains all subtypes of glutamate receptors23,24 and because long-term potentiation of synaptic transmission occurs in this structure25,26. We find that four or more distinct single-channel currents are evoked by applying glutamate to each outside-out membrane patch. These conductances vary in their ionic permeability and in the agonist most effective in causing them to open. Clear transitions between all the conductance levels are observed. Our observations are compatible with the model that all the single channel conductances activated by glutamate reflect the operation of one or two complex molecular entities.
686 citations
TL;DR: It is shown that a membrane phosphoprotein initially studied independently by several laboratories and given different designations, is in fact the same protein, which may play a general role in the formation of synaptic relationships during development or regeneration, and a continuing role inThe functional modulation of certain synapses throughout life.
522 citations
TL;DR: The results demonstrate a marked impairment of LTP in hippocampal explants taken from rats exposed to stress, and the significance of this result with respect to cellular mechanisms underlying the relationship between stress, cognition, and learning is discussed.
457 citations
TL;DR: It is reported for the first time that NMDA receptors of the dentate gyms become actively involved in synaptic transmission following long-lasting neuronal changes induced by daily electrical stimulation (kindling) of the amygdala or hippocampal commissures.
Abstract: In the mammalian central nervous system, receptors for the excitatory amino-acid neurotransmitters are divided into three subtypes depending on their sensitivity to three specific agonists: kainate, quisqualate and N-methyl-D-aspartate (NMDA). The ionophores operated by NMDA are gated by Mg2+ in a voltage-dependent manner and allow passage of several cations, including Ca2+ which may be important in plastic alterations of neuronal excitability. Indeed, specific antagonists of NMDA receptors effectively block spatial learning, long-term potentiation and some animal models of chronic epilepsy. Despite their abundance on central neurons, NMDA receptors, with a few noteworthy exceptions, do not generally seem to be involved in low-frequency synaptic transmission. Here we report for the first time that NMDA receptors of the dentate gyrus, where they do not normally contribute to the generation of synaptic potentials, become actively involved in synaptic transmission following long-lasting neuronal changes induced by daily electrical stimulation (kindling) of the amygdala or hippocampal commissures. In contrast to controls, the excitatory postsynaptic potentials (e.p.s.ps) of granule cells in hippocampal slices obtained from kindled animals displayed characteristics typical of an NMDA-receptor-mediated component. The involvement of NMDA receptors in synaptic transmission may underlie the long-lasting changes in neuronal function induced by kindling.
384 citations
TL;DR: Developmental and regeneration-associated changes in GAP-43 synthesis appear to be mediated largely at the level of transcription of a single gene, and among several tissues and cells examined, Gap-43 mRNA is expressed only in neurons.
355 citations
TL;DR: Injection of the active enzyme elicited long-lasting enhancement of synaptic transmission, similar to LTP, whereas inactivated kinase failed to do so and the observed changes included an increased amplitude of the excitatory post-synaptic potential and an increased probability of firing and a reduced latency of the associated actin potential.
Abstract: Long-term potentiation (LTP) in the hippocampus is an interesting example of synaptic plasticity because of its induction by physiological discharge rates and its long duration1,2. Of the possible biochemical mechanisms that regulate prolonged changes in cell function, protein phosphorylation is a particularly attractive candidate3. We have therefore examined the effect of intracellular injection of calcium/diacylglycerol-dependent protein kinase (protein kinase C (PKC)) in CA1 pyramidal neurones in hippocampal slices. Injection of the active enzyme elicited long-lasting enhancement of synaptic transmission, similar to LTP, whereas inactivated kinase failed to do so. The observed changes included an increased amplitude of the excitatory post-synaptic potential (e.p.s.p.) and an increased probability of firing and a reduced latency of the associated actin potential.
335 citations
TL;DR: It is reported that during the critical period in young kittens, a selective NMDA-receptor antagonist blocks visual responses of cortical neurons much more effectively than it does in the adult cat, suggesting that NMDA receptors may be involved in establishing synaptic plasticity in the kitten visual cortex.
Abstract: Acidic amino acids, such as glutamate and aspartate, are thought to be excitatory transmitters in the cerebral neocortex and hippocampus1–8. Receptors for these amino acids can be classified into at least three types on the basis of their agonists. Quisqualate-preferring receptors and kainate-preferring receptors are implicated in the mediation of synaptic transmission in many regions including the hippocampus9,10 and visual cortex11, whereas N-methyl-D-aspartate (NMDA)-preferring receptors are thought to be involved in modulating synaptic efficacy, for example in long-term potentiation, a form of synaptic plasticity in the hippocampus12–14. In the visual cortex of the cat and monkey, it is well established that synaptic plasticity, estimated by susceptibility of binocular responsiveness of cortical neurons to monocular visual deprivation, disappears after the 'critical' period of postnatal development15–17. Here we report that during the critical period in young kittens, a selective NMDA-receptor antagonist blocks visual responses of cortical neurons much more effectively than it does in the adult cat. This suggests that NMDA receptors may be involved in establishing synaptic plasticity in the kitten visual cortex.
TL;DR: It is reported here that noradrenaline produces an enhancement in the activity of voltage-dependent calcium channels in granule cells of the hippocampal dentate gyrus, mediated by β-adrenoceptors and can be mimicked by cyclic AMP.
Abstract: The predominance of unconventional transmitter release sites at noradrenaline-containing synapses and the diffuse projections of noradrenaline-containing fibres originating in locus coeruleus have led to speculation that noradrenaline may act as a neuromodulator in the central nervous system. Evidence suggests that it has a modulatory function in the plasticity of the developing nervous system, in controlling behavioural states of an organism, and in learning and memory. Recently, Hopkins and Johnston demonstrated that noradrenaline enhances the magnitude, duration and probability of induction of long-term potentiation (LTP) at mossy fibre synapses in the hippocampal formation, and LTP is widely believed to be a cellular substrate for aspects of memory. To investigate the membrane effects of noradrenaline on central neurons, we used a newly developed preparation in which patch-clamp techniques can be applied to exposed adult cortical neurons. We report here that noradrenaline produces an enhancement in the activity of voltage-dependent calcium channels in granule cells of the hippocampal dentate gyrus. This action appears to be mediated by beta-adrenoceptors and can be mimicked by cyclic AMP.
TL;DR: D(-)Aminophosphonovalerate, a specific antagonist of the N-methyl-D-aspartate subtype of glutamate receptor, was perfused through a push-pull cannula into the dentate gyrus of rats anaesthetized with urethan in order to observe its effect on the induction and maintenance of long-term potentiation and on the increase in release of endogenous glutamate associated with long- term potentiation.
TL;DR: These findings represent the first demonstration that PKC inhibitors prevent persistence of potentiation and suggest thatPKC regulates the persistence of synaptic enhancement beginning after its onset, and that PKc's role decreases with time after the induction of enhancement.
TL;DR: Cal calcium levels have been studied by numerically solving the appropriate electro-diffusion equations for two different postsynaptic structures by assuming voltage-dependent calcium channels are present on dendritic spines and that a short, but high-frequency, burst of presynaptic activity is more effective in raising levels of calcium and especially of the calcium-calmodulin complex than sustained low-frequency activity.
Abstract: Increased levels of intracellular calcium at either pre- or postsynaptic sites are thought to precede changes in synaptic strength. Thus, to induce long-term potentiation in the hippocampus, periods of intense synaptic stimulation would have to transiently raise the levels of cytosolic calcium at postsynaptic sites--dendritic spines in the majority of cases. Since direct experimental verification of this hypothesis is not possible at present, calcium levels have been studied by numerically solving the appropriate electro-diffusion equations for two different postsynaptic structures. Under the assumption that voltage-dependent calcium channels are present on dendritic spines, free intracellular calcium in spines can reach micromolar levels after as few as seven spikes in 20 milliseconds. Moreover, a short, but high-frequency, burst of presynaptic activity is more effective in raising levels of calcium and especially of the calcium-calmodulin complex than sustained low-frequency activity. This behavior is different from that seen at the soma of a typical vertebrate neuron.
TL;DR: MK-801 blocked selectively the N-methyl-D-aspartate receptor-mediated component of synaptic transmission, which can be recorded in response to single shock stimulation of the Schaffer collateral-commissural pathway in the absence of added Mg2+ to the perfusate.
TL;DR: Evidence is provided that rapid learning of a specific cue potentiates cortical synapses in a defined terminal field as shown in rats trained on a series of two-odor discriminations.
TL;DR: The results indicate that E‐S potentiation results from an increase in the level of depolarization reached by a synaptic potential of given initial slope, which supports the hypothesis that tetanization induces greater l.t.p.s. of excitatory inputs onto pyramidal cells than of inputs onto feed‐forward inhibitory interneurones.
Abstract: 1. Tetanization of hippocampal pyramidal cell afferents travelling in stratum radiatum of area CA1 induces both long-term potentiation (l.t.p.) of extracellularly recorded excitatory postsynaptic potentials (e.p.s.p.s), and an increase in the number of cells firing, as measured by the extracellular population spike, for a given sized field e.p.s.p. The mechanism of this latter change, known as e.p.s.p.-spike (E-S) potentiation, was investigated in the guinea-pig hippocampal slice preparation. 2. Plots of the E-S relation before and after tetanization were constructed from measures taken over a series of stimulus strengths. Tetanization of afferents in stratum radiatum decreased the spike threshold by 24%, while the gamma-aminobutyric acid antagonist picrotoxin (PTX) decreased spike threshold by 72%. Sequential administration of PTX and tetanization, in either order, resulted in no more change in the E-S threshold than did PTX application alone. 3. Extracellular synaptic potentials, matched for initial slope before and after tetanization by adjusting the stimulus strength, showed an increased peak amplitude and increased peak latency following tetanization. PTX produced similar but larger percentage changes. Tetanization in the presence of PTX, however, did not alter the field potential wave shape. 4. Intracellular postsynaptic potentials (p.s.p.s) were also matched for initial slope before and after tetanization. Tetanization induced p.s.p. shape changes similar to those observed extracellularly, i.e. in the direction of less inhibition. Such changes did not occur in the presence of PTX. 5. Inhibitory p.s.p.s (i.p.s.p.s) were studied in depolarized pyramidal cells with microelectrodes filled with QX-314. Tetanization of afferents in stratum radiatum produced i.p.s.p. increases in eight of nineteen cells. These increases were generally attributable to an increased activity in the recurrent inhibitory pathway. Tetanization of the alveus failed to produce any lasting increases in the i.p.s.p. amplitude. 6. Tetanization of afferents in stratum radiatum decreased the ratio of the intracellular i.p.s.p. to field e.p.s.p. over stimulus strengths below population spike threshold. Above population spike threshold, the ratio tended towards its pretetanization level. 7. The results indicate that E-S potentiation results from an increase in the level of depolarization reached by a synaptic potential of given initial slope. These findings support the hypothesis that tetanization induces greater l.t.p. of excitatory inputs onto pyramidal cells than of inputs onto feed-forward inhibitory interneurones.
TL;DR: Findings indicate that the steroid anaesthetic alphaxalone is able to directly activate Cl‐ conductance normally activated by GABA in spinal neurones, which may be partly responsible for the depressant actions of alPHaxalone on the mammalian central nervous system.
Abstract: 1. Intracellular recordings from cultured rat spinal cord neurones demonstrated that Cl(-)-dependent responses to GABA (gamma-aminobutyric acid) (but not glycine) were increased in amplitude and duration by the steroid anaesthetic alphaxalone (3 alpha-hydroxy-5 alpha-pregnane-11,20-dione) at submicromolar concentrations that produced little or no effect on passive electrical properties. The non-anaesthetic 3 beta-hydroxy analogue was without effect on GABA-evoked responses. 2. Under voltage clamp, membrane currents evoked by GABA were potentiated by alphaxalone without change in the reversal potential for the GABA-evoked response. Fluctuation analysis of GABA-evoked currents suggested that the mean open-time of GABA-activated channels was prolonged from 30 to 74 ms in the presence of the anaesthetic. 3. Higher concentrations of alphaxalone, similar to those reported during surgical anaesthesia, increased membrane conductance in the absence of exogenously applied GABA. Under voltage clamp, current responses to alphaxalone reversed at the same potential as did responses to GABA, suggesting that they result from increased Cl- conductance. 4. Alphaxalone responses were reduced by the GABA antagonist bicuculline. Fluctuation analysis of current responses to the anaesthetic suggest that they result from the activation of ion channels of long (100 ms) open-time and elementary conductance indistinguishable from that of channels activated by GABA (20 pS). Taken together, these findings indicate that the steroid anaesthetic is able to directly activate Cl- conductance normally activated by GABA in spinal neurones. 5. The actions of the steroid at GABA-receptor-Cl(-)-channel complexes are similar to those produced by the anaesthetic barbiturates (e.g. pentobarbitone), although obtained at 50-100-fold lower concentrations. These effects on the inhibitory Cl(-)-conductance mechanism may be partly responsible for the depressant actions of alphaxalone on the mammalian central nervous system.
TL;DR: Findings show that LLP in the neocortex is a postsynaptic phenomenon which requires conjunctive pre- and post Synaptic activity, adequate levels of intracellular free calcium, and functional intrace cellular transport.
TL;DR: The results raised the possibility that the input from the sensory cortex participates in motor learning and retention of the learned motor skills.
TL;DR: This chapter discusses the possibility that proteolytic digestion of cytoskeletal proteins, in particular spectrin, is part of the mechanisms through which physiological activity elicits structural and chemical changes in brain synapses.
TL;DR: Reduction of extracellular Mg2+ concentration induced spontaneous and evoked epileptiform activity in the entorhinal cortex (EC) and dentate gyrus (DG) of combined hippocampus (HC)-EC slices and the neurotransmitter norepinephrine (NE), which has previously been shown to modulate long-term potentiation in the DG, was found to exhibit differential modulation of epilepsyptiformActivity in the EC and DG.
TL;DR: Data support a role for NE in regulating long-term plasticity of both granule cell action potential firing and dendritic EPSPs in the dentate gyrus.
TL;DR: Bicuculline-induced cell bursts in CA3 resulted in long-term potentiation of the CA1 response, suggesting that the naturally occurring hippocampal sharp waves may reflect events analogous to artificially induced LTP.
TL;DR: The present study explored the mechanism of cis-unsaturated fatty acid action on LTP produced by perforant path stimulation and proposed that high-frequency stimulation produces an elevation of intracellular Ca2+, which then triggers phospholipase A2-mediated oleate release, which could act in synergy with processes that render PKC oleates-sensitive to produce a persistent activation of PKC, which is critical for and leads to the persistence of the LTP response.
Abstract: Previous correlative and interventive work from this laboratory has suggested that activation of protein kinase C (PKC) is important for the maintenance of the hippocampal long-term potentiation (LTP) response. One such study demonstrated that application of the cis-unsaturated fatty acid, oleate, a newly discovered PKC activator, could prolong the time course of LTP. The present study explored the mechanism of cis-unsaturated fatty acid action on LTP produced by perforant path stimulation. First, neither oleate application nor high-frequency stimulation alone produced a persistent change in synaptic transmission, while the 2 in conjunction did so. This suggests that oleate acts synergistically with the consequences of this stimulation to produce an enhancement of the LTP response. Second, oleate enhancement of LTP was more potent when applied in the perforant path synaptic terminal zone than in the dentate hilus, implying that the site of oleate action is at the synapse (where PKC is reported to be enriched). Third, translocation of PKC activity to the membrane was significantly increased after oleate-enhanced LTP relative to vehicle controls. PKC translocation was found to be unaltered by oleate application alone. Fourth, mepacrine blockade of the Ca2+-dependent enzyme phospholipase A2, which releases endogenous oleate from membrane phospholipids, inhibited the time-course of a persistent LTP response. This inhibition was shown to be reversible with oleate application. We propose that high-frequency stimulation produces an elevation of intracellular Ca2+, which then triggers phospholipase A2-mediated oleate release. This free oleate then could act in synergy with processes that render PKC oleate-sensitive to produce a persistent activation of PKC, which is critical for and leads to the persistence of the LTP response.
TL;DR: Xenopus oocytes injected with messenger RNA isolated from primary cultures of rat brain have been used to study NMDA receptors and should facilitate the quantitative study of the regulation of NMDA receptor activation and serve as a tool for purification of the encoding messenger RNA.
Abstract: N-methyl-D-aspartate (NMDA) activates a class of excitatory amino acid receptor involved in a variety of plastic and pathological processes in the brain. Quantitative study of the NMDA receptor has been difficult in mammalian neurons, because it usually exists with other excitatory amino acid receptors of overlapping pharmacological specificities. Xenopus oocytes injected with messenger RNA isolated from primary cultures of rat brain have now been used to study NMDA receptors. The distinguishing properties of neuronal NMDA receptors have been reproduced in this amphibian cell, including voltage-dependent block by magnesium, block by the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid, and potentiation by glycine. This preparation should facilitate the quantitative study of the regulation of NMDA receptor activation and serve as a tool for purification of the encoding messenger RNA.
TL;DR: The duration of long-term potentiation of the CA1 evoked field potential in rat hippocampal slices was significantly modulated by pre-treatment of slices with delta-9-tetrahydrocannabinol (THC), suggesting that one possible action of THC may be in modulating hippocampal electrophysiology and its role in short-term memory processes.
TL;DR: Brief application of MCD to the CA1 region of hippocampal slices induces long-term potentiation, that is, a long-lasting increase in the efficacy of synaptic transmission, indistinguishable from the classical LTP produced by trains of high-frequency electrical stimulation.
Abstract: Long-term potentiation of synaptic transmission in the hippocampus induced by a bee venom peptide
TL;DR: Results indicate that LTP at EC-DG synapses cannot represent the mechanism of kindling following EC stimulation, however, synaptic potentiation at this site can facilitate the development of epileptogenesis in response to subsequent activation of the perforant path.