A possible correlate of the postsynaptic condition for long-lasting potentiation in the guinea pig hippocampus in vitro (original) (raw)
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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.
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...
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.