A possible correlate of the postsynaptic condition for long-lasting potentiation in the guinea pig hippocampus in vitro (original) (raw)
Related papers
Neuroscience, 1986
The effects of the ~-methyl-~aspartate receptor antagonists 2-amino-S-phosphonovalerate and y-u-glutamylglycine on the induction of long-lasting potentiation in the CA1 and dentate areas of the hippocampal slice preparation have been examined. Synaptic activity was recorded extracellularly in the dendritic layer as a field excitatory postsynaptic potential, and the amount of long-lasting potentiation produced was measured from the change in slope of the rising phase of this potential. Experiments were generally perfo~ed with the y-aminobutyric acid antagonist picrotoxin in the solution. It is shown that 2-amino-S-phosphonovalerate prevents the induction of long-lasting potentiation following afferent tetanization of an input, without any effect on other inputs projecting to the same postsynaptic neurons. This result makes it unlikely that the preventive action of 2-amino-5-phosphonovalerate is related to any unspecific depressive action. Instead, 2-amino-5-phosphonovale~te was observed to block a postsynaptic depolarizing process appearing during the tetanus, likely related to current through synaptically activated N-methyl-o-aspartate receptor channels. It is suggested that 2-amino-5-phosphonovalerate prevents the induction of long-lasting potentiation by blockade of these currents through its antagonistic action on the N-methyl-D-aspartate receptors, Application of ~-D-glutamylglycine similarly prevented the induction of long-tasting potentjation. No potentiation appeared following wash-out of the drug. The results exclude the possibility that the preventive action of this drug is related to a mere masking action on long-lasting potentiation induced in presynaptic terminals. It is suggested that y-n-glutamylglycine blocks the induction of long-lasting potentiation by its antagonistic action on the N-methyl-D-aspartate receptors, i.e. in a manner similar to that of 2-amino-5-phosphonovaierate.
Post-tetanic depression of GABAergic synaptic transmission in rat hippocampal cell cultures
Neuroscience Letters, 2002
The effect of tetanic stimulation (30 Hz, 4 s) on evoked GABAergic inhibitory postsynaptic currents (IPSCs) was studied in cell cultures of dissociated hippocampal neurons with established synaptic connections. It was found that tetanic stimulation elicited post-tetanic depression (PTD) of the evoked IPSCs with a duration of more than 50 s in about 60% of the connections tested; post-tetanic potentiation was induced in 25% of the connections. We propose that the opposite effects of tetanization on IPSC amplitude are due to differences in the type of the interneuron that was tetanized. Since PTD in our experiments was usually accompanied by changes in the IPSC coefficient of variation and changes of a paired pulse depression, which are thought to reflect presynaptic mechanisms of modulation, we suggest that part of the PTD is due to a presynaptic mechanism(s).
Neuron, 1992
The induction of long-term potentiation (LTP) in hippocampal CA1 pyramidal cells requires a rise in postsynaptic intracellular Ca2+ concentration ([Ca2+]i). To determine the time for which Ca2+ must remain elevated to induce LTP, the photolabile Ca2+ buffer diazo-4 was used to limit the duration of the rise in postsynaptic [Ca2+]i following a tetanus. The affinity of diazo-4 for Ca2+ increases approximately 1600-fold upon flash photolysis, permitting almost instantaneous buffering of [Ca2+]i without disturbing resting [Ca2+]i prior to the flash. Photolysis of diazo-4 1 s following the start of the tetanus blocked LTP, while delaying photolysis for more than 2 s had no discernible effect on LTP. Photolyzing diazo-4 at intermediate delays (1.5-2 s) or reducing photolysis of diazo-4 often resulted in short-term potentiation (STP). These results indicate that a tetanus-induced rise in postsynaptic [Ca2+]i lasting at most 2-2.5 s is sufficient to generate LTP. Smaller increases or shorte...
The Journal of Physiology, 1993
1. Inhibitory cell activity and inhibitory postsynaptic potentials impinging spontaneously on pyramidal cells were recorded in the CA3 region of hippocampal slices from guinea-pig. We compared the effects on synaptic inhibition, of tetanic stimuli in the presence of antagonists of ionotropic excitatory amino acid receptors, and of application of agonists of metabotropic glutamate receptors. 2. Tetanic stimulation of afferent fibres caused an increase, of duration 0 52-5 min, in the frequency of spontaneous Cl--mediated IPSPs. Inhibitory cell firing increased due to a depolarization and a reduction of after-hyperpolarizing potentials. 3. Tetanic stimulation induced, in some experiments, rhythmic bursts of IPSPs and transformed the firing pattern of some inhibitory cells from a discharge of single action potentials to rhythmic bursts of three to five action potentials. 4. Application of the metabotropic glutamate receptor agonist, trans-1-amino- cyclopentane-1,3-dicarboxylic acid (tACPD), at concentrations from 3-10/,M in- creased the frequency of spontaneous IPSPs. In some slices tACPD caused IPSPs to occur rhythmically. IPSP frequency did not continue to increase with concentrations of tACPD above 20 /LM. 5. tACPD depolarized inhibitory cells and reduced after-hyperpolarizing potentials. High concentrations (50-100 ,tM) of tACPD excited inhibitory cells to potentials at which they no longer discharged fast action potentials. 6. Both tetanic stimulation and tACPD led to the appearance in pyramidal cell pairs of simultaneous IPSPs which were not previously observed, suggesting that the same group of inhibitory cells was excited in both cases. 7. Low concentrations of tACPD (3-10 /tM) enhanced IPSP responses to tetanic stimuli, while the effects of tetanic stimuli were occluded in the presence of high concentrations (20-30 #M) of tACPD. 8. We suggest that activation of metabotropic glutamate receptors during tetanic stimulation leads to a post-tetanic excitation of inhibitory cells that mediate Cl-dependent IPSPs.
Brain Research, 2000
Long-term potentiation (LTP) of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components of 'dual-component' field excitatory postsynaptic potentials (fEPSP-A and fEPSP-N) was studied in the CA1 stratum radiatum in hippocampal slices of rats. Relative degrees of LTP of these fEPSP components were compared for tetanizations with low and high strengths. Magnitudes of fEPSP-A and fEPSP-N were estimated in parallel with a least-square fitting of a short-latent (0.1-8.8 ms) fragment of evoked responses by a weighted sum of 'basic' fEPSP-A and fEPSP-N, obtained during a short preliminary application of d-2-amino-5-phosphonovalerate (APV). We found that low-strength tetanizations selectively potentiated fEPSP-A, while high strength tetanizations potentiated both fEPSP components. These results demonstrate in the experiments with parallel measurements of fEPSP-A and fEPSP-N that LTP of these components differ depending on the strength of afferent tetanization. Unequal potentiation of the commissural-collateral and excitatory local-circuit synapses, which presumably contain different amounts of the AMPA and NMDA receptors, is discussed as the most probable explanation for these results.
Trends in Neurosciences, 1993
In many brain areas, including the cerebellar cortex, neocortex, hippocampus, striatum and nucleus accumbens, brief activation of an excitatory pathway can produce long-term depression (L TD) of synaptic transmission. In most preparations, induction of LTD has been shown to require a minimum level of postsynaptic depolamation and a rise in the intracellular Ca 2+ concentration [Ca2+] i in the postsynaptic neurone. Thus, induction conditions resemble those described for the initiation of associative long-term potentiation (LTP). However, data from structures susceptible to both L TD and L TP suggest that a stronger depolarization and a greater increase in [Ca2 +]i are required to induce LTP than to initiate LTD. The source of Ca 2+ appears to be less critical for the differential induction of LTP and LTD than the amplitude of the Ca 2+ surge, since the activation of voltage-and ligand-gated Ca 2+ conductances as well as the release from intracellular stores have all been shown to contribute to both L TD and L TP induction. L TD is induceable even at inactive synapses if [Ca2+]i is raised to the appropr~te level by antidromic or heterosynaptic activation, or by raising the extracellular Ca 2+ concentration [Ca2+] o. These conditions suggest a rule (called here the ABS rule) for activity-dependent synaptic modifications that differs from the classical Hebb rule and that can account for both homosynaptic LTD and LTP as well as for heterosynaptic competition and associativity.
Biochemical and Biophysical Research Communications, 1991
The effects of adenosine A2 receptor antagonist (CP-66713) on long-term potentiation were studied using guinea pig hippocampal slices in a perfusion system. Tetanic stimulation of Schaffer collateral input which was applied during perfusion of CP-66713 (10 PM), did not induce long-term potentiation but rather long-term depression of evoked synaptic potentials (field EPSP), but induced long-term potentiation of the population spike in CA1 neurons. Thus, adenosine derivatives which accumulate in the synaptic cleft during the tetanic stimulation may be involved in induction of the long term potentiation via A2 receptors at the synapse. The clear discrimination between long-term depression of the field EPSP and long-term potentiation of the population spike suggests EPSP-spike potentiation at the postsynaptic sites. o 1991 Academrc pre5s, Inc.
Neuroscience Letters, 1995
To elucidate the role of calcium release from internal stores during different paradigms of tetanisation in long-term potentiation (LTP), we have investigated the effects of thapsigargin on the elevation of the excitatory postsynaptic field potential (fEPSP) and the population spike (PS) after tetanisation. We found no effect on the duration of fEPSP potentiation if thapsigargin was perfused before strong (triple) tetanisation. However, the potentiation was reduced significantly from control experiments if thapsigargin was applied before weak (single) tetanisation. Surprisingly, we did not find any reduction of PS potentiation, which could be due to changes in the recurrent inhibition. We conclude that the involvement of internal calcium release in the mechanisms of LTP induction will be reduced if multiple tetanisation is used.
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Neuroscience, 1986
The effects of the ~-methyl-~aspartate receptor antagonists 2-amino-S-phosphonovalerate and y-u-glutamylglycine on the induction of long-lasting potentiation in the CA1 and dentate areas of the hippocampal slice preparation have been examined. Synaptic activity was recorded extracellularly in the dendritic layer as a field excitatory postsynaptic potential, and the amount of long-lasting potentiation produced was measured from the change in slope of the rising phase of this potential. Experiments were generally perfo~ed with the y-aminobutyric acid antagonist picrotoxin in the solution. It is shown that 2-amino-S-phosphonovalerate prevents the induction of long-lasting potentiation following afferent tetanization of an input, without any effect on other inputs projecting to the same postsynaptic neurons. This result makes it unlikely that the preventive action of 2-amino-5-phosphonovalerate is related to any unspecific depressive action. Instead, 2-amino-5-phosphonovale~te was observed to block a postsynaptic depolarizing process appearing during the tetanus, likely related to current through synaptically activated N-methyl-o-aspartate receptor channels. It is suggested that 2-amino-5-phosphonovalerate prevents the induction of long-lasting potentiation by blockade of these currents through its antagonistic action on the N-methyl-D-aspartate receptors, Application of ~-D-glutamylglycine similarly prevented the induction of long-tasting potentjation. No potentiation appeared following wash-out of the drug. The results exclude the possibility that the preventive action of this drug is related to a mere masking action on long-lasting potentiation induced in presynaptic terminals. It is suggested that y-n-glutamylglycine blocks the induction of long-lasting potentiation by its antagonistic action on the N-methyl-D-aspartate receptors, i.e. in a manner similar to that of 2-amino-5-phosphonovaierate.
Onset Characteristics of Long-Term Potentiation in the Guinea-Pig Hippocampal CA1 Region in Vitro
European Journal of Neuroscience, 1989
The temporal development of long-term potentiation (LTP) was examined in the CA1 region of the hippocampal slice preparation (bath temperature 3OOC). LTP was evoked by a single brief afferent tetanus (3 -40 impulses at 50 Hz) given in the presence of picrotoxin (to facilitate LTP induction). Short-lasting potentiation processes unrelated to LTP were excluded by comparing the potentiation obtained in picrotoxin solution with that obtained in normal solution or in the presence of the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovalerate. LTP was also evoked by pairing single test volleys with brief (2 -3 impulses) heterosynaptic tetani in picrotoxin solution. Both methods showed no significant rise of LTP until about 3 s after the induction event. LTP thereafter developed almost linearly towards a peak within 20 -25 s after the tetanus, the time course being practially independent of the induction method and of the relative amount of LTP evoked. The latency and rise time of LTP depended on bath temperature, being about twice as long at 25OC as at 3OOC. Following the peak, LTP rapidly decayed to less than half its peak value in 8 min, the decay tending to be less with longer trains. The LTP component reaching its peak 20 -25 s after a tetanus was practically occluded after a saturating homosynaptic tetanization, and was only partially recovered 1 h afterwards. The latency to the onset of LTP suggests an indirect coupling between the calcium influx, presumed to trigger the potentiation, and the expression of LTP. The independence of the early time course with respect to the induction strength indicates that the intervening system@) operates in a linear manner.
Neuroscience Letters, 1985
The sensitivity of convulsant-induced epileptiform activity in the hippocampus to the selective Nmethyl-t>aspartate (NMDA) antagonist t~-2-amino-5-phosphonovalerate (D-APV) was examined using in vitro electrophysiological techniques. This compound reduced the number and size of the synaptically evoked population spikes recorded in the CA1 region in the presence of the convulsants, pentylenetetrazol, bicuculline or folate. Intracellular recordings in the presence of bicuculline showed that D-APV reduced the late component of the excitatory postsynaptic potential and the number of action potentials evoked synaptically. A mechanism is suggested to explain how NMDA receptors, which are known not to be involved in normal synaptic transmission in hippocampal slices, can contribute to epileptiform activity.
Does mismatch negativity have utility for NMDA receptor drug development in depression?
Brazilian Journal of Psychiatry, 2022
Rapid antidepressant effects associated with ketamine have shifted the landscape for the development of therapeutics to treat major depressive disorder (MDD) from a monoaminergic to glutamatergic model. Treatment with ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, may be effective, but has many non-glutamatergic targets, and clinical and logistical problems are potential challenges. These factors underscore the importance of manipulations of binding mechanics to produce antidepressant effects without concomitant clinical side effects. This will require identification of efficient biomarkers to monitor target engagement. The mismatch negativity (MMN) is a widely used electrophysiological signature linked to the activity of NMDA receptors (NMDAR) in humans and animals and validated in pre-clinical and clinical studies of ketamine. In this review, we explore the flexibility of the MMN and its capabilities for reliable use in drug development for NMDAR antagonists in MDD. We supplement this with findings from our own research with three distinct NMDAR antagonists. The research described illustrates that there are important distinctions between the mechanisms of NMDAR antagonism, which are further crystallized when considering the paradigm used to study the MMN. We conclude that the lack of standardized methodology currently prevents MMN from being ready for common use in drug discovery.
The 1980s: d-AP5, LTP and a Decade of NMDA Receptor Discoveries
Neurochemical Research, 2018
In the 1960s and 70s, biochemical and pharmacological evidence was pointing toward glutamate as a synaptic transmitter at a number of distinct receptor classes, known as NMDA and non-NMDA receptors. The field, however, lacked a potent and highly selective antagonist to block these putative postsynaptic receptors. So, the discoveries in the early 1980s of d-AP5 as a selective NMDA receptor antagonist and of its ability to block synaptic events and plasticity were a major breakthrough leading to an explosion of knowledge about this receptor subtype. During the next 10 years, the role of NMDA receptors was established in synaptic transmission, long-term potentiation, learning and memory, epilepsy, pain, among others. Hints at pharmacological heterogeneity among NMDA receptors were followed by the cloning of separate subunits. The purpose of this review is to recognize the important contributions made in the 1980s by Graham L. Collingridge and other key scientists to the advances in our understanding of the functions of NMDA receptors throughout the central nervous system.
PLOS Computational Biology, 2018
Learning in biologically relevant neural-network models usually relies on Hebb learning rules. The typical implementations of these rules change the synaptic strength on the basis of the co-occurrence of the neural events taking place at a certain time in the pre-and postsynaptic neurons. Differential Hebbian learning (DHL) rules, instead, are able to update the synapse by taking into account the temporal relation, captured with derivatives, between the neural events happening in the recent past. The few DHL rules proposed so far can update the synaptic weights only in few ways: this is a limitation for the study of dynamical neurons and neural-network models. Moreover, empirical evidence on brain spike-timing-dependent plasticity (STDP) shows that different neurons express a surprisingly rich repertoire of different learning processes going far beyond existing DHL rules. This opens up a second problem of how capturing such processes with DHL rules. Here we propose a general DHL (G-DHL) rule generating the existing rules and many others. The rule has a high expressiveness as it combines in different ways the pre-and post-synaptic neuron signals and derivatives. The rule flexibility is shown by applying it to various signals of artificial neurons and by fitting several different STDP experimental data sets. To these purposes, we propose techniques to pre-process the neural signals and capture the temporal relations between the neural events of interest. We also propose a procedure to automatically identify the rule components and parameters that best fit different STDP data sets, and show how the identified components might be used to heuristically guide the search of the biophysical mechanisms underlying STDP. Overall, the results show that the G-DHL rule represents a useful means to study time-sensitive learning processes in both artificial neural networks and brain.
Related papers
Neuroscience, 1995
The present study deals with the question of whether L-type voltage-gated calcium channels can support the induction of input specific long-term potentiation. Tetanus-induced potentiation of synaptic transmission was examined in the CA 1 region of normal and disinhibited guinea-pig hippocampal slices. It was found that afferent tetanization in the presence of 50~tM of the N-methyl-o-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid led to a prolonged input specific potentiation. This potentiation was found only in disinhibited slices, its induction required cooperativity, and it was associated with an increase in the early part of the field excitatory postsynaptic potential initial slope. It was not affected by the L-type voltage-gated calcium channel blocker nifedipine, but it was reduced when o(-)-2-amino-5-phosphonopentanoic acid was supplemented with other N-methyl-D-aspartate receptor antagonists. The present study also examined a potentiation that was not restricted to the activated synapses and that was not associated with an increase in the early part of the field excitatory postsynaptic potential initial slope. This potentiation was blocked by the L-type voltage-gated calcium channel antagonist nifedipine.
Neuroscience, 1999
We investigated mechanisms involved in the modulation of long-term potentiation by low concentrations of N-methyl-d-aspartate in the CA1 region of rat hippocampal slices. When applied for 5 min prior to and during tetanic stimulation, 1 mM N-methyl-d-aspartate inhibited long-term potentiation induction. Studies examining paired-pulse facilitation of non-N-methyl-d-aspartate receptor-mediated synaptic responses suggest that the effects of N-methyl-d-aspartate result in part from a presynaptic mechanism. This conclusion is supported by the observation that 1 mM N-methyl-d-aspartate failed to diminish N-methyl-d-aspartate receptor-mediated synaptic currents and that agents that enhance glutamate release, including high extracellular concentrations of calcium and an adenosine A1 receptor antagonist, overcome the long-term potentiation inhibition. Furthermore, the calcineurin inhibitors, FK-506 and cyclosporin A, as well as the phosphatase 1 and 2A inhibitor, okadaic acid, blocked the effects of Nmethyl-d-aspartate on long-term potentiation suggesting a role for phosphatase activation in modulating the induction of long-term potentiation. These results show that the inhibition of long-term potentiation by untimely N-methyl-d-aspartate receptor activation is reversed by treatments that enhance glutamate release and suggest that adenosine release and diminished calcium influx during tetanic stimulation coupled with phosphatase activation contribute to the modulation of synaptic plasticity.
Slow presynaptic and fast postsynaptic components of compound long-term potentiation
The Journal of …, 2007
Long-term potentiation (LTP) mediates learning and memory in the mammalian hippocampus. Whether a presynaptic or postsynaptic neuron principally enhances synaptic transmission during LTP remains controversial. Acute hippocampal slices were made from transgenic mouse strains that express synaptopHluorin in neurons. SynaptopHluorin is an indicator of synaptic vesicle recycling; thus, we monitored functional changes in presynaptic boutons of CA3 pyramidal cells by measuring changes in synaptopHluorin fluorescence. Simultaneously, we recorded field excitatory postsynaptic potentials to monitor changes in the strength of excitatory synapses between CA3 and CA1 pyramidal neurons. We found that LTP consists of two components, a slow presynaptic component and a fast postsynaptic component. The presynaptic mechanisms contribute mostly to the late phase of compound LTP, whereas the postsynaptic mechanisms are crucial during the early phase of LTP. We also found that protein kinase A (PKA) and L-type voltage-gated calcium channels are crucial for the expression of the presynaptic component of compound LTP, and NMDA channels are essential for that of the postsynaptic component of LTP. These data are the first direct evidence that presynaptic and postsynaptic components of LTP are temporally and mechanistically distinct.
1997
The phenomenon of long-term potentiation is widely used as an experimental model of memory. An approach that has been used to study its underlying mechanisms is to analyse its interaction with presynaptic paired-pulse facilitation. Several studies found no evidence for an interaction in the CA1 hippocampal area, whereas other data, for example from quantal analysis, suggested that presynaptic mechanisms contribute to the maintenance of long-term potentiation. In the present study, initial slopes of field potentials in area CA1 were measured in rat hippocampal slices. ''Conventional'' long-term potentiation was induced by high-frequency (100 Hz) afferent tetanization of the testing input. ''Associative'' long-term potentiation was induced by combining lower frequency (40 Hz) tetanization of a testing input with high-frequency tetanization of a second input. The paired-pulse facilitation ratio decreased in the majority of experiments in which long-term potentiation was induced conventionally, but it decreased, increased or did not change after inducing associative potentiation. Decreases in the paired-pulse facilitation correlated inversely with the initial (pre-tetanic) facilitation ratio. A more detailed regression analysis suggests that this correlation results from two other correlations: (i) that between changes in paired-pulse facilitation and the magnitude of long-term potentiation, and (ii) that between initial paired-pulse facilitation and the magnitude of long-term potentiation. The first correlation prevailed during the initial 10 min following tetanization, while the second prevailed 40-60 min later.
Neuroscience, 1998
In the CA1 area of the hippocampus, low frequency and tetanic conditioning stimuli are known to trigger long-term depression and potentiation of synaptic responses respectively and to produce irreversible excitatory postsynaptic potential/spike potentiation, i.e. an increase of the probability of discharge of the neurons. Using simultaneous extracellular recordings in stratum radiatum and stratum pyramidale in the CA1 area of the rat hippocampus, brief application of the K + channel blocker tetraethylammonium resulted both in long-term potentiation of synaptic responses and in excitatory postsynaptic potential/spike potentiation that could be reversed by subsequent low frequency or tetanic stimuli. Excitatory postsynaptic potential/spike potentiation and its subsequent reversal by an electrical conditioning stimulus were found to have an N-methyl--aspartate receptor-independent component. We conclude that the reversal of excitatory postsynaptic potential/spike potentiation can occur and that it does not require the induction of long-term modification of synaptic responses. 1998 IBRO.
Neurophysiological analysis of long-term potentiation in mammalian brain
Behavioural Brain Research, 1995
Long-term potentiation (LTP) is a persistent increase in postsynaptic response following a high-frequency presynaptic activation. Characteristic LTP features, including input specificity and associativity, make it a popular model to study memory mechanisms. Mechanisms of LTP induction and maintenance are briefly reviewed. Increased intracellular Ca 2+ concentration is shown to be critical for LTP induction. This increase is believed to be based on Ca 2 + influx secondary to activation of N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Existence of other sources of Ca 2 + increase and other critical factors is now becoming evident. They include voltage-dependent Ca 2 + channels, Ca 2 + intracellular stores, metabotropic glutamate receptors, 'modulatory' transmitters. An example of an involvement of voltage-dependent Ca 2 ÷ channels is potentiation induced by intracellular depolarizing pulses. LTP can be divided into decremental earlier (E-LTP) and non-decremental late (L-LTP) phases which explains some inconsistencies in studies of LTP mechanisms. E-LTP is suggested to be based on a transient increase in presynaptic release probabilities. A hypothesis is considered which explains L-LTP by suggesting that Ca 2 + activates structural changes leading to an increase in the synaptic gap resistance. This enhances positive synaptic electrical feedback and augments release probability. The hypothesis predicts specific morphological changes, synchronous transmitter release of two or several quanta in some central synapses and the amplification of such synchronization following LTP induction. Data are discussed which maintain these predictions.
Onset Characteristics of Long-Term Potentiation in the Guinea-Pig Hippocampal CA1 Region in Vitro
European Journal of Neuroscience, 1989
The temporal development of long-term potentiation (LTP) was examined in the CA1 region of the hippocampal slice preparation (bath temperature 3OOC). LTP was evoked by a single brief afferent tetanus (3 -40 impulses at 50 Hz) given in the presence of picrotoxin (to facilitate LTP induction). Short-lasting potentiation processes unrelated to LTP were excluded by comparing the potentiation obtained in picrotoxin solution with that obtained in normal solution or in the presence of the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovalerate. LTP was also evoked by pairing single test volleys with brief (2 -3 impulses) heterosynaptic tetani in picrotoxin solution. Both methods showed no significant rise of LTP until about 3 s after the induction event. LTP thereafter developed almost linearly towards a peak within 20 -25 s after the tetanus, the time course being practially independent of the induction method and of the relative amount of LTP evoked. The latency and rise time of LTP depended on bath temperature, being about twice as long at 25OC as at 3OOC. Following the peak, LTP rapidly decayed to less than half its peak value in 8 min, the decay tending to be less with longer trains. The LTP component reaching its peak 20 -25 s after a tetanus was practically occluded after a saturating homosynaptic tetanization, and was only partially recovered 1 h afterwards. The latency to the onset of LTP suggests an indirect coupling between the calcium influx, presumed to trigger the potentiation, and the expression of LTP. The independence of the early time course with respect to the induction strength indicates that the intervening system@) operates in a linear manner.
The role of inhibitory mechanisms in hippocampal long-term potentiation
Neuroscience Letters, 1984
The role of inhibitory processes in long-term potentiation (LTP) was investigated in hippocampal slices of the rat. GABAergic inhibition, tested by double shock experiments and by intracellular recording of inhibitory postsynaptic potentials, was not reduced in CA 1 pyramidal neurones after the induction of LTP. In cells recorded with caesium chloride-filled electrodes LTP could not be elicited. A reduction of intrinsic potassium-dependent inhibition may thus be responsible for LTP.
A prolonged post-tetanic hyperpolarization in rat hippocampal pyramidal cells in vitro
Brain Research, 1990
The post-tetanic sequelae of trains of synaptic stimuli (50 pulses at 5 or 10 Hz) were studied with intraceUular recordings from rat hippocampal neurons in vitro. In a large proportion of CA1 neurons, stimulation of afferent fibers was followed by a prolonged membrane hyperpolarization (peak amplitude approximately 6 mV) that was associated with a decrease in neuronal input resistance (approximately 33%) that lasted from tens of seconds to over 1 min. Antidromic stimulation or activation of cells with intracellular current injection did not elicit this post-tetanic hyperpolarization (PTH). The PTH could be elicited in chloride (Cl-)-loaded cells, its null potential shifted in response to changes in extracellular potassium ([K+]o), and it was significantly reduced by 5-10 mM extracellular cesium (Cs+). The K+-dependent PTH may also be calcium (Ca 2+) dependent as its amplitude and associated conductance increase were sensitive to changes in [Ca 2+]o. The PTH was enhanced by treatments that increase Ca 2+ entry into cells including perfusion with elevated [Ca2+]o, with picrotoxin or with tetraethylammonium ion (TEA). The K ÷ conductance blocker 4-AP had no consistent effect on the PTH. The PTH was potently blocked by the membrane-permeant forms of cAMP, dibutyryl-and 8-bromo-cAMP. However, phorbol esters that activate protein kinase C and carbachol, which usually block the same potential that is blocked by cAMP, did not depress the PTH. The cardiac glycosides dihydro-ouabain and strophanthidin had only small and variable effects on the PTH. We suggest that prolonged synaptic stimulation activates a novel K + conductance that may be important in regulating the membrane potential during periods of repetitive neuronal firing in many hippocampal neurons.
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