Showing papers on "Long-term potentiation published in 1983"
TL;DR: Results indicate that the synaptic receptor in the Schaffer collateral‐commissural pathway may be of the kainate or quisqualate type and although NMA receptors do not appear to be involved in normal synaptic transmission in this pathway they may play a role in synaptic plasticity.
Abstract: 1. The effects of excitatory amino acids and some antagonists applied by ionophoresis to stratum radiatum in the CA1 region of rat hippocampal slices were examined on the locally recorded field e.p.s.p. evoked by stimulation of the Schaffer collateral-commissural projection. 2. L-glutamate, L-aspartate and the more potent and selective excitatory amino acids quisqualate, kainate and N-methyl-DL-aspartate (NMA) depressed the e.p.s.p., presumably through depolarization and/or a change in membrane conductance. 3. The depression induced by kainate considerably outlasted the period of ejection whereas NMA depressions were rapidly reversible and were often followed by a potentiation of the e.p.s.p. In higher doses NMA also depressed the presynaptic fibre volley. The possible involvement of these effects in neurotoxicity and synaptic plasticity is raised. 4. The selective NMA antagonist, DL-2-amino-5-phosphonovalerate (APV) applied in doses which abolished responses to NMA, had no effect on the e.p.s.p. but prevented long term potentiation (l.t.p.) of synaptic transmission evoked by high frequency stimulation of the Schaffer collateral-commissural pathway. Other antagonists which had little or no effect on normal synaptic transmission included D-alpha-aminoadipate (DAA), the optical isomers of 2-amino-4-phosphonobutyrate (APB) and L-glutamate diethylester (GDEE). 5. In contrast, gamma-D-glutamylglycine (DGG), applied in amounts which affected quisqualate and kainate actions as well as those of NMA, was an effective synaptic antagonist whilst having no effect on the presynaptic fibre volley. 6. These results indicate that the synaptic receptor in the Schaffer collateral-commissural pathway may be of the kainate or quisqualate type. Although NMA receptors do not appear to be involved in normal synaptic transmission in this pathway they may play a role in synaptic plasticity. The interaction of L-glutamate and L-aspartate with these receptors is discussed.
2,236 citations
TL;DR: It is reported that intracellular injections of the calcium chelator EGTA block the development of LTP and this results strongly suggest that LTP is caused by a modification of the postsynaptic neurone and that its induction depends on the level of free calcium.
Abstract: Hippocampal long-term potentiation (LTP) is a remarkably stable facilitation of synaptic responses resulting from very brief trains of high-frequency stimulation. Because of its persistence and modest induction conditions, LTP represents a promising candidate for a substrate of memory. Some progress has been made in localizing the changes responsible for the effect; for example, it has been shown that LTP is not accompanied by changes in the fibre volleys of the test afferents or by generalized alterations of the dendrites of their target cells. However, it is unknown whether the potentiation is due to pre- or postsynaptic changes and there is evidence in favour of each (for example, see refs 5, 6). We now report that intracellular injections of the calcium chelator EGTA block the development of LTP. These results strongly suggest that LTP is caused by a modification of the postsynaptic neurone and that its induction depends on the level of free calcium.
1,095 citations
TL;DR: The nature of the associative process permissive for the induction of long-term potentiation is discussed and the conclusion that perfect temporal contiguity is not a requirement of this prototypical elemental memory unit is concluded.
789 citations
TL;DR: The result indicates that the potentiation produced by kindling may be based upon the same mechanism as the LTP effect, and the effect of this potentiation on subsequent tests of short-term and long-term potentiation.
562 citations
TL;DR: It is suggested that modifiable excitatory synapses necessary for learning have been identified in studies of long-term potentiation and are distinct from those of 'usual' short-term post-tetanic potentiation.
482 citations
TL;DR: Study of long-lasting potentiation in the hippocampal slice preparation (CA1 region) in conditions where postsynaptic inhibition was reduced by application of γ-aminobutyric acid (GABA) receptor blockers found that in addition to their direct effect on inhibition, GABA blockers dramatically facilitated the induction ofLong- lasting potentiation.
Abstract: A long-lasting potentiation of synaptic transmission can be induced in the hippocampus by high-frequency stimulation of the afferent fibres1,2. This process has been regarded as a possible physiological substrate for long-term memory. From theoretical considerations on memory function it has been proposed that synaptic strengthening occurs as a result of simultaneous pre- and postsynaptic activation3, a principle which has been used in several theoretical models (for references see refs 4, 5). It thus seems important to study factors which control hippocampal long-lasting potentiation and, in particular, whether these factors act pre- or postsynaptically. A presynaptic control of long-lasting potentiation was established in experiments where two separate inputs to the same population of CA1 pyramidal cells were used6,7. Studies on the granule cell population of area dentata however, revealed, a heterosynaptic modulation of the generation of potentiation, suggesting a possible postsynaptic control also8,9. We have now studied long-lasting potentiation in the hippocampal slice preparation (CA1 region) in conditions where postsynaptic inhibition was reduced by application of γ-aminobutyric acid (GABA) receptor blockers. We found that in addition to their direct effect on inhibition, GABA blockers dramatically facilitated the induction of long-lasting potentiation. The results indicate involvement of postsynaptic mechanisms in the generation of long-lasting potentiation.
369 citations
TL;DR: Results indicated that kindling increased, rather than reduced, inhibition in the dentate gyrus, suggesting an enhanced resistance to inhibitory failure.
296 citations
TL;DR: Results show that monoamines can modulate long‐term changes in synaptic function in the dentate gyrus, and suggest that 5‐HT is more potent in this respect than NA, and the effect of monoamine depletion on granule cell excitability was investigated.
Abstract: 1. Brief, high-frequency stimulation of the perforant path results in a long-term potentiation (l.t.p.) of the field response evoked in the dentate gyrus by single shocks to the perforant path. We have compared the magnitude and duration of l.t.p. in normal, anaesthetized rats with animals depleted of noradrenaline (NA), 5-hydroxytryptamine (5-HT), or both. 2. All animals were exposed to an identical sequence of eight high-frequency trains of increasing intensity given over a period of 140 min to the perforant path of one hemisphere. The potential evoked by test shocks to the perforant path was monitored in both hemispheres throughout this period and for a further 96 min after the last train. 3. Plots of the mean potentiation of the population e.p.s.p. as a function of time were computed for all animals in each group. L.t.p. in the NA-depleted group was about 50% of that in the non-depleted control group throughout the course of the experiment. L.t.p. in the 5-HT-depleted group was more severely affected; mean potentiation did not exceed 30% of that in the control group at any time. 4. The duration of l.t.p. was unaffected by NA depletion and reduced by 5-HT depletion. 5. The threshold for the intensity of high-frequency current pulses necessary to elicit l.t.p. was unaffected by NA depletion and raised by 5-HT depletion. 6. Short-term potentiation of the population e.p.s.p. was unaffected by either NA depletion or 5-HT depletion. 7. The effect of monoamine depletion on granule cell excitability was investigated. 5-HT depletion, but not NA depletion, induced an increase in the excitability of the granule cell population, in the sense that a population e.p.s.p. of a given size was associated with a larger population spike. 8. Long-term potentiation of granule cell excitability was not affected by NA depletion, but was reduced by 5-HT depletion. 9. These results show that monoamines can modulate long-term changes in synaptic function in the dentate gyrus, and suggest that 5-HT is more potent in this respect than NA.
290 citations
TL;DR: The number of large, concave spine synapses with large postsynaptic densities significantly increases in the central zone of synaptic activation, and this zone is postulated to mediate associative potentiation.
280 citations
TL;DR: This form of long-term synaptic potentiation (LTP), known as associative LTP, was shown in some cases to last hours without decrement and could not be accounted for by any of several measured postsynaptic passive membrane properties.
Abstract: Interactions between two excitatory monosynaptic inputs to hippocampal neurons of the CA1 region were examined in the in vitro slice By adjusting the strengths of the electrical stimuli delivered to the two input pathways, one was made to generate a weak and the other a strong synaptic response Simultaneous tetanic stimulation of both input pathways resulted in a subsequent long-term enhanced synaptic efficacy in the weak input under conditions in which the same tetanic stimulation of either input alone failed to have this effect This form of long-term synaptic potentiation (LTP), known as associative LTP, was shown in some cases to last hours without decrement The plastic changes were localized within the CA1 region and appear to reside in the pre- or postsynaptic elements of the monosynaptic excitatory input to the pyramidal neurons The increased synaptic efficacy could not be accounted for by any of several measured postsynaptic passive membrane properties
266 citations
TL;DR: It is reported that tetanization of either MPP or LPP reliably depresses synaptic transmission in the other pathway for at least 3 h, considerably smaller than the usual magnitude of LTP, and was obtained regardless of whether LTP had been produced in the tetanized homosynaptic pathway.
Abstract: All synaptically-based neuropsychological theories of learning postulate that there are changes resulting from neural activity which are long-lasting and confined to specific sets of synapses1–3. In the past decade a form of synaptic strengthening known as long-term potentiation (LTP) has been found which results from high-frequency neural activity and is of sufficient duration to model as a learning mechanism4,5. Some early tests of the synaptic specificity of LTP in area CA1 of the hippocampus indicated that although LTP was specific to the tetanized pathway, in a converging untetanized pathway it was associated with depression of synaptic transmission lasting for at least 30 min6–8. However, others have found that this heterosynaptic depression more usually decays within 5–15 min post-tetanus despite the maintenance of LTP in the tetanized pathway9–13. Similarly, in the dentate gyrus (DG), LTP of either the lateral (LPP) or medial (MPP) components of the perforant path afferents has been associated with only short-lasting reciprocal heterosynaptic depression14. Here, using more detailed measurement of stimulus intensity curves, we report that tetanization of either MPP or LPP reliably depresses synaptic transmission in the other pathway for at least 3 h. This heterosynaptic depression, considerably smaller than the usual magnitude of LTP, was obtained regardless of whether LTP had been produced in the tetanized homosynaptic pathway. Heterosynaptic long-term depression was not observed if the test pathway had been previously tetanized.
TL;DR: The electrical properties of a cortical (spiny) pyramidal cell were analysed on the basis of passive cable theory from measurements made on histological material and the conclusions hold within a wide range of values of electrical parameters, provided that the membrane is passive.
Abstract: The electrical properties of a cortical (spiny) pyramidal cell were analysed on the basis of passive cable theory from measurements made on histological material (C. Koch, T. Poggio & V. Torre, Phil. Trans. R. Soc. Lond. B 298, 227-264 (1982)). The basis of this analysis is the solution of the cable equation for an arbitrary branched dendritic tree. The conclusions, however, hold within a wide range of values of electrical parameters, provided that the membrane is passive. We determined the potential at the soma as a function of the synaptic input (transient conductance changes) and as a function of the spine neck dimensions, following a suggestion by W. Rall (Brain Inf. Serv. Res. Rep. 3, 13-21 (1974); Studies in neurophysiology (ed. R. Porter), pp. 203-209 (Cambridge University Press, 1978)) that the spine neck might be an important determinant in regulating the efficiency of synapses on spines. From our investigation four major points emerge. (i) Spines may effectively compress the effect of each single excitatory synapse on the soma, mapping a wide range of inputs onto a limited range of outputs (nonlinear saturation). This is also true for very fast transient inputs, in sharp contrast with the case of a synapse on a dendrite. (ii) The somatic depolarization due to an excitatory synapse on a spine is a very sensitive function of the spine neck length and diameter. Thus the spine can effectively control the attenuation of its input via the dimensions of the neck, thereby setting the shape of the resulting saturation curve. There is an optimal neck diameter for which variations of the neck are most effective in controlling the weight of the excitatory spine synapse. For reasonable parameter values this optimal value is consistent with anatomical data. This might be the basic mechanism underlying ultra-short memory, long-term potentiation in the hippocampus or learning in the cerebellum. (iii) Spines with shunting inhibitory synapses on them are ineffective in reducing the somatic depolarization due to excitatory inputs on the dendritic shaft or on other spines. Thus isolated inhibitory synapses on a spine are not expected to occur. (iv) The conjunction of an excitatory synapse with a shunting inhibitory synapse on the same spine may result in a time-discrimination circuit with a temporal resolution of around 100 $\mu $s.
TL;DR: At 39% of the potentiated sites norepinephrine application resulted in long-lasting potentiation (LLP), suggesting a role for NE inLong-term hippocampal plasticity.
TL;DR: The thesis here developed is that the influx of calcium ions across the membrane of the granule pyramidal cells plays the key role in the generation of long-term potentiation, and the proposed combination of calcium with calmodulin will account for the hypothesis of Marr that cognitive memory is due to conjunction potentiation.
TL;DR: Receptor binding estimates of the number of GABA and associated benzodiazepine receptors were made in several brain regions following kindling, suggesting a possible mechanism for the kindling-induced enhancement of inhibition observed in previous evoked potential experiments.
TL;DR: It is suggested that the enhanced production of long-lasting potentiation in inhibition-free slices is related to an increased postsynaptic depolarization in granule cell dendrites.
TL;DR: Long-term potentiation of CA1 population spikes was elicited by cCA3 stimulation and Phencyclidine and ketamine blocked the potentiation in a dose-dependent manner while diazepam and sodium thiopental had no effect.
TL;DR: Findings provide a link between learning-induced physiological plasticity and LTP, and demonstrate that the auditory system can develop long term potentiation.
TL;DR: Results from experiments on developing animals, suggested that the circadian influence on LTP in either area was not present before postnatal day 20 and it is important to note that circadian influences on hippocampal LTP are preserved in the in vitro environment where tonic extrahippocampal input has presumably been removed.
TL;DR: The sigma opiate, cyclazocine, also prevented the induction of LTP in vitro while morphine and procaine were ineffective while mu and kappa opiates and the antagonist naloxone were ineffective.
TL;DR: Results may indicate a presynaptic action of APB, possibly mediated via an effect on Presynaptic calcium availability, that reduces lateral perforant path responses with kynurenic acid but does not have a similar effect on PPP.
Abstract: The glutamate analogue 2-amino-4-phosphonobutyric acid (APB) has been shown to selectively reduce synaptic transmission along the lateral portion of the perforant path input to the dentate gyrus APB is studied here with respect to effects on paired-pulse potentiation (PPP) along the perforant path Application of APB causes a reduction in lateral perforant path responses, but also an increase in the %PPP of that response The effect does not result simply from reducing response size, because the amount of potentiation of matched first responses increases, and also because APB reduces the potentiated response proportionately less than a comparable first response A similar effect is seen by decreasing extracellular calcium Reducing lateral perforant path responses with kynurenic acid, which apparently acts on postsynaptic sites, does not have a similar effect on PPP These results may indicate a presynaptic action of APB, possibly mediated via an effect on presynaptic calcium availability
Dissertation•
01 Nov 1983
TL;DR: The postnatal development of short-term potentiation (STP) and LTP (LIP) was examined in the neocortex and dentate gyrus of the rat.
Abstract: The postnatal dev~loPment of short-term potentiation (STP) and .~ long-term potentiation (LIP) were examined in the neocortex and dentate , gyrus of the rat. It was. found that STP and LTP develop during narrowly , defined time periods in both systems. This functional synaptic development development formation). did not appear to~correspond well with known structural I I~ in either system (e.g. synaptogenesis or dendritic sp~ne Stimula~n of callosal fibers produced a biphasic, positive, negative, transcallosal response (TCR).recorded near the surface of the-anterior neocortex in all ages tested. The tCR showed a decrease in threshold, latency and halfwidth, and an increase in pea~ amplitude with age. STP and LTP of the TCR could not be reliablr detected until after PN16 and PN18, respectively. The magnitude of STP and LTP was initbttly , small out approached adult levels rapidly after their initial appearance. Stimulation of perforant path fibers produced a positive !!: excitatory post-synaptic potential (EPSP) with a s~per-imposed negative population spike recorded in the dentate hilus. The EPSP showed a decrease in threshold, latency and halfwid~, and an increase in peak amplitude with age. STP and LTP (of the EPSP and/or population spike) could not be reliably detected until the second postnatal week, with STP appearing pr10r to LTP. Again, STP and LTP approached adult levels rapidly after their initial appearance. These resurts could not be
TL;DR: The effects of naloxone on potentiation of CA3 pyramidal cell field potentials induced by tetanization of the mossy fiber pathway was studied and it was concluded that an opioid peptide is probably involved in the generation of the potentiation.
TL;DR: A greater degree of long-term potentiation was obtained when adjacent afferents to the stratum radiatum of CA1 were co-actively conditioned, as compared to that observed with activation of a single pathway alone.
Abstract: Long-term potentiation of synaptic responses in the hippocampus is a unique form of physiological plasticity which can be induced by brief episodes of repetitive afferent activity and which can persist for days or months. The present study describes cooperative (or associative) interactions among afferents to the stratum radiatum of CA1 for the induction and maintenance of this phenomenon. A greater degree of long- term potentiation was obtained when adjacent afferents to the stratum radiatum were co-actively conditioned, as compared to that observed with activation of a single pathway alone. This cooperativity was not the result of increased postsynaptic discharge during conditioning, as shown by the absence of greater long-term potentiation following orthodromic and antidromic co-activation of the postsynaptic CA1 pyramidal cells.
TL;DR: The results suggest that one effect of kainate may be to produce dendritic depolarisation in CA1 pyramidal neurones, which may underlie the ability ofkainate (and folate) to elicit seizures and distant brain damage.
Abstract: The actions of kainic acid on excitatory synaptic responses in rat hippocampal slices have been investigated and compared with the effects of other excitatory amino acids. Kainate administered iontophoretically or via the superfusate produced a large and long lasting potentiation of the population spike evoked in the CA1 region by Schaffer collateral-commissural stimulation. This potentiation was associated with a reduction in the field EPSP recorded in the dendritic region (stratum radiatum) but with no change in the presynaptic fibre volley or with any long lasting alteration in the antidromic population spike. The results suggest that one effect of kainate may be to produce dendritic depolarisation in CA1 pyramidal neurones. Kainate in equivalent amounts elicited similar potentiations of the population spike recorded in the dentate gyrus in response to either lateral or medial perforant path stimulation. Smaller amounts of kainate than those required to affect either CA1 or dentate pathways were able to potentiate the mossy fibre-evoked population spike in the CA3 region. Folic acid, which shares kainate's ability to produce seizures and distant brain damage when injected into the brain, elicited similar potentiations of synaptic excitation. Higher doses of folate than of kainate were required which is consistent with its weaker epileptogenic actions in vivo. In contrast, N-methyl-aspartate, ibotenate, L-glutamate and L-aspartate were unable to mimic kainate's potentiating action. In higher doses the substances depressed the population spike for long periods. These data suggest that potentiation of synaptic events may underlie the ability of kainate (and folate) to elicit seizures and distant brain damage.
TL;DR: A high intensity, high frequency train applied to the perforant path during perfusion with the adenosine agonist 2-chloroadenosine, was markedly attenuated in its ability to produce long-term potentiation.
TL;DR: The results indicate that amphetamine can enhance the development of LTP under some but not all testing procedures.
Abstract: Long term potentiation (LTP) has received considerable attention as a neurophysiological analog of memory. Amphetamine, as well as several other catecholamine agonists, can enhance behaviorally-assessed memory storage in a variety of training situations. The present experiments tested the effects of amphetamine on LTP produced by high frequency stimulation of the perforant path in rats. The results indicate that amphetamine can enhance the development of LTP under some but not all testing procedures. Studies of the neurobiological bases by which central and peripheral catecholamines modulate memory storage may be augmented by examinations of catecholamine effects on a specific form of long-lasting change in brain function. Similarly, the ability to manipulate LTP may prove to be an important aid in examinations of neurobiological correlates of this phenomenon.
TL;DR: This paper quantifies the term in the equation which expresses the role of presynaptic activity, which can express both synaptic potentiation and depression as a function of the afferent frequency of the particular synapse under consideration.
TL;DR: With parameters constrained to match the properties of alpha-motoneurons and group Ia synaptic input, EPSP amplitudes were most sensitive to changes in synaptic density and were much less sensitive to alterations in neuron input resistance and specific membrane resistivity when synaptic density was constant.
Abstract: We have used a computer-based mathematical model of alpha-motoneurons and of group Ia synaptic input to them, based on anatomical and electrophysiological data from the cat spinal cord, in order to examine the effects of variations in neuron size and input resistance and of conductance magnitude and duration on the generation of excitatory postsynaptic potentials (EPSPs). The first set of calculations were designed to test the possible role of nonlinear EPSP summation in producing a differential distribution of posttetanic potentiation of group Ia EPSPs, described in the preceding paper (25; see also Refs. 26, 27). The results suggest that the negative correlations observed between the degree of posttetanic potentiation of Ia EPSPs and initial (pretetanic) EPSP amplitude as well as with the input resistance of the postsynaptic motoneurons can be explained in part by the inherent non-linearity between conductance change and the resultant potential change at chemical synapses. In a second set of calculations, we used the same model system to evaluate the effects produced by variations in neuronal membrane area, input resistance, and specific membrane resistivity, as well as of the density of excitatory synaptic input on the peak amplitude of EPSPs. With parameters constrained to match the properties of alpha-motoneurons and group Ia synaptic input, EPSP amplitudes were most sensitive to changes in synaptic density and were much less sensitive to alterations in neuron input resistance and specific membrane resistivity when synaptic density was constant.
TL;DR: It was concluded that interictally maintained changes in defensiveness were dependent on a form of lasting synaptic potentiation of excitatory activity from the amygdala to the ventromedial hypothalamus, and an equally lasting attenuation of function due to increased recurrent inhibition in the ventral hippocampus.