Long-term Potentiation In Slices Research Articles

Dopamine favours the emergence of long-term depression versus long-term potentiation in slices of rat prefrontal cortex

In the present study, we have investigated possible interactions between dopamine and long-term changes in synaptic efficacy induced in layer V pyramidal cells by tetanization of afferents from layer I–II. In the absence of dopamine, we confirmed that high frequency stimulation of excitatory afferents induced long-term potentiation, long-term depression or no change. Inversely, in the presence of dopamine, we have found that the same tetanus led to long-term depression in synaptic transmission in a majority of cells, but no more long-term potentiation. These results suggest that in rat prefrontal cortex, dopamine may determine the direction of activity dependent changes in synaptic efficacy and therefore, plays a fundamental role in the physiology of this structure.

Roles of endogenous cholinergic neurons in the induction of long-term potentiation at hippocampal mossy fiber synapses

To evaluate the functional role of endogenous acetylcholine (ACh) in the induction of long-term potentiation (LTP) at mossy fiber-CA3 synapses, the influence of cholinergic hypofunction on it was investigated. Administration of a cholinergic neurotoxin, ethylcholine mustard aziridinium ion (AF64A; 5 nmol, i.c.v.), to guinea pigs one week prior to preparing slices resulted in a significant decrease in the magnitude of LTP, associated with a significant decrease in cholineacetyltransferase (ChAT) activity and the number of ChAT immunoreactive cells in the hippocampal slices. Bath-application of a cholinesterase inhibitor, physostigmine at 0.1 μM and 10 μM, attenuated and augmented, respectively, the magnitude of LTP in slices prepared from vehicle-treated animals (naive slices), whereas that in slices prepared from AF64A-treated animals (lesioned slices) was not significantly affected by physostigmine at any concentration tested. The induction of LTP in naive slices was inhibited or facilitated by a muscarinic M 1 antagonist pirenzepine (1 μM) and by an M 2 antagonist AF-DX 116 (1 μM) alone, respectively, whereas that in lesioned slices was not significantly changed by either of them. Furthermore, bath-applied carbachol (CCh) at 0.01–10 μM augmented the magnitude of LTP in lesioned slices, whereas the induction of LTP in naive slices was inhibited and facilitated by CCh at 0.01–0.1 μM and 1–10 μM, respectively, as reported previously. Such an augmentation of LTP by CCh was reversed by pirenzepine, but not by AF-DX 116. These observations suggest that AF64A induces the defect in ACh release and the hypofunction of M 2 receptors, but not of M 1, at least during the induction of LTP at mossy fiber-CA3 synapses. Thus, it is conceivable that endogenous ACh plays a facilitatory and inhibitory role through muscarinic M 1 and M 2 receptors in the induction of LTP in the mossy fiber-CA3 pathway.

Synaptic potentiation and depression in slices of mediorostral neostriatum-hyperstriatum complex, an auditory imprinting-relevant area in chick forebrain

Long-term potentiation, a tetanic stimulation-evoked, persistent increase in synaptic efficiency, is the most extensively studied form of synaptic plasticity. Intracellular correlates of long-term potentiation have been analysed in mammalian hippocampus and cortex, but not in bird cortical analogues. We present here studies on long-term potentiation in slices of the chick forebrain area mediorostral neostriatumhyperstriatum complex which receives thalamic afferents and is relevant for auditory filial imprinting. Following afferent tetanic stimulation, population spike potentiation was extracellularly recorded in 25% of the tested neurons for longer than 40 min. Using intracellular recordings, the membrane potential, the amplitude of excitatory postsynaptic potentials, the latency between the test stimulus and the evoked action potentials, and the cellular excitability (excitatory postsynaptic potential-spike relationship) were found to change after the tetanus. A long-term depression following the tetanus was also seen in some units in this area. Furthermore, the mechanisms underlying long-term potentiation were investigated. A large depolarization of resting membrane potential (approx. 36 mV) was characteristic after the tetanic stimulation. N-methyl- daspartate receptor channels are necessary for induction of this depolarization, as well as for long-term potentiation, as demonstrated by the effect of dl-2-amino-5-phosphonovaleric acid. After intracellular recordings, the cells were injected with Lucifer Yellow. The combination of electrophysiological characterization and morphological identification suggested that the potentiation came chiefly from type I neurons, which have the largest soma among the neuron types in this area and up to eight dendrites. The results demonstrate that the recognized major phenomena of long-term potentiation are found in an auditory imprinting-relevant area of the chick forebrain, and that this potentiation is dependent on N-methyl- d-aspartate receptor channels. It is noteworthy that behavioural imprinting was previously shown to induce a reduction of up to 47% of the spine frequency of type I neurons and a growth of the remaining spine synapses, all resembling a synaptic selection process. Therefore, the intriguing possibility emerges that mechanisms underlying long-term potentiation are instrumental for this selection process, which involves regressive and proliferative morphological changes.

The suppression of long-term potentiation in rat hippocampus by inhibitors of nitric oxide synthase is temperature and age dependent

At room temperature (23°C–25°C), the induction of long-term potentiation (LTP) in area CA1 of slices from young male Sprague-Dawley rats was depressed by preincubation with the nitric oxide synthase inhibitors N G-nitro- l-arginine ( l-NA, 100 μM) and N G-nitro- l-arginine methyl ester ( l-NAME, 100 μM). The d isomers were ineffective under the same conditions. Hemoglobin (20 μM) reduced but did not completely block LTP. Neither l-NA (at concentrations up to 1 mM) nor hemoglobin (20 μM) had any significant effect on LTP in slices from adult rats at room temperature, or in young rats at 29°C–30°C. These results suggest that nitric oxide is unlikely to play a role in the induction of LTP under physiological conditions.

Benzodiazepines block long-term potentiation in slices of hippocampus and piriform cortex

The effects of two benzodiazepines, diazepam and triazolam, on long-term potentiation were tested in slices of hippocampus and piriform cortex. The drugs had little influence on baseline synaptic responses but both were very effective in blocking LTP elicited by theta pattern stimulation. The effects were fully reversible upon washout. Diazepam reduced the increase in burst responses that occurs during theta stimulation and thus appears to interfere with the initial triggering events for long-term potentiation. This may reflect the enhancing action of the drug on GABA-mediated inhibitory potentials. Triazolam did not detectably change the burst responses elicited by theta pattern stimulation. Experiments with slices of piriform cortex indicated that triazolam also failed to disrupt the development of long-term potentiation but instead caused the potentiation to decay back to baseline in 15–30 min. Triazolam thus seems to act on the mechanisms that stabilize long-term potentiation. These results provide a possible explanation for the amnestic effects of benzodiazepines in humans and animals and support the hypothesis that long-term potentiation contributes to memory encoding.

Investigation of β-adrenergic modulation of synaptic transmission and postsynaptic induction of associative LTP in layer V neurones in slices of rat sensorimotor cortex

Long-term potentiation (LTP) of synaptic transmission is considered to be a neuronal model of learning. Recently, the probability of induction of associative LTP in layer V cells in sensorimotor neocortex was shown to be much higher in the awake cat than in the slice preparation. We hypothesised that the loss of extrinsic noradrenergic activity in the slice might account for this difference, particularly since a β-adrenergic enhancement of field potentials has been seen in this preparation. We therefore bath-applied noradrenaline (NA) or the β 1-adrenergic agonist, isoprenaline (ISO) to elucidate the cellular basis of the enhancement of field potentials, and to see if the drugs increased the probability of induction of associative LTP in slices. We found that NA and ISO produced a dose-dependent, reversible reduction of spike accommodation and an increase in excitability but had no effect on the depolarizing slope or peak amplitude of sub-threshold EPSPs, and that drug application did not increase the probability of induction of LTP. We conclude that: (1) the enhancement of field potentials and late components of EPSPs (7) can be explained by the known actions of β-adrenergic drugs on membrane currents in layer V cells, and (2) the lower probability of induction of associative LTP in slices cf. the awake cat cannot be due solely to the loss of noradrenergic activity.

Agonists of cholinergic and noradrenergic receptors facilitate synergistically the induction of long-term potentiation in slices of rat visual cortex

Acetylcholine (ACh) and noradrenaline (NA) have been shown to facilitate experience-dependent modifications of synaptic connectivity during postnatal development of the kitten visual cortex. To further investigate the mechanisms of this facilitation we studied the effects of these neuromodulators in an in vitro model of use-dependent synaptic plasticity. We have chosen long-term potentiation (LTP) in rat visual cortex slices because it shares several features with the in vivo model. In both cases induction of synaptic modifications requires that postsynaptic activation reaches a critical threshold and in both cases changes are induced more easily in young animals and when N-methyl- d-aspartate (NMDA) receptor-gated conductances are activated. Intracellular recordings were obtained from regular spiking cells in supragranular layers of rat visual cortex and LTP was induced by tetanic stimulation of the underlying white matter. Both cholinergic and noradrenergic agonists raised the probability that tetanic stimuli induced LTP and as in vivo they acted synergistically. These effects were mediated by agonists of muscarinic and β-receptors, respectively. The agonists of both receptor systems enhanced the depolarizing response to the tetanus and increased NMDA receptor-gated conductances during this response. We suggest that this mode of action also accounts for the facilitatory effects which ACh and NA have on use-dependent synaptic plasticity in the developing visual cortex.

A facilitatory role of endogenous somatostatin in long-term potentiation of the mossy fiber-CA3 system in guinea-pig hippocampus

To estimate the functional role of endogenous somatostatin in the production of long-term potentiation (LTP) in mossy fiber-CA3 system, an influence of depletion of somatostatin on the magnitude of it was examined in guinea-pig hippocampal slices. Administration of cysteamine (200 mg/kg, s.c.), a depletor of somatostatin, to guinea-pigs 13 h prior to preparing slices resulted in a significant decrease in the magnitude of LTP of population spikes in mossy fiber-CA3 system, being associated with a significant depletion of the content of somatostatin in the hippocampus. Furthermore, bath-applied somatostatin (1–14) at a concentration, at which the substance did not influence LTP in slices prepared from saline-treated animals, significantly augmented LTP in slices from cysteamine-treated animals. Cyclo-somatostatin (0.32 and 3.2 μM), a putative antagonist of somatostatin receptors, failed to affect the magnitude of LTP of mossy fiber-CA3 system when applied alone; however, the combined application of cyclo-somatostatin with somatostatin (0.32 μM) significantly inhibited the augmenting action of somatostatin on LTP. From these observations, it is suggested that endogenous somatostatin plays a facilitatory role in the production of LTP in mossy fiber-CA3 system in guinea-pig hippocampus.

Effects of thyrotropin-releasing hormone and a related analog, CNK-602A, on long-term potentiation in the mossy fiber-CA3 pathway of guinea pig hippocampal slices

The effects of thyrotropin-releasing hormone (TRH) and a related analog, CNK-602A, that induces the release of catecholamines, on long-term potentiation (LTP) of the population spike in mossy fiber-CA3 pathways were investigated in guinea pig hippocampal slices. TRH augmented LTP of the population spike at concentrations of 10(-6)-10(-5) M. CNK-602A also augmented LTP at concentrations of 10(-6)-10(-5) M in a dose-dependent manner. LTP in slices of the hippocampus obtained from animals given 6-hydroxydopamine (6-OHDA) intraventricularly was significantly lower than that in non-treated animals. However, both TRH and CNK-602A (10(-6) M) augmented LTP in slices from 6-OHDA-treated animals. These findings suggest that TRH and CNK-602A augment LTP in the mossy fiber-CA3 pathway without activating noradrenergic and/or dopaminergic fibers.

Effects of isoproterenol, a β-adrenergic agent, on susceptibility to undergo long-term potentiation in slices from the adult rat visual cortex

Effects of isoproterenol, a β-adrenergic agent, on susceptibility to undergo long-term potentiation in slices from the adult rat visual cortex

A 1-heteroaryl-4-piperidinyl-methyl pyrrolidinone, BMY 21502, delays the decay of hippocampal synaptic potentiation in vitro

The effects of the substituted pyrrolidinone, BMY 21502, on the properties of cell membranes, synaptic transmission and synaptic plasticity, were assessed in area CA 1 of hippocampal slices from the rat. Application of the compound to the bath had no consistent direct effects on parameters of the cell membrane or evoked synaptic potentials, at concentrations of less than 30 μM. In a blind experimental design, BMY 21502 at 1.0 and 10 μM, but not 25 μM, significantly delayed the decay of long-term potentiation in slices obtained from young animals; in slices obtained from very old rats (2.5–3.2 yr), 10 μM BMY 21502 significantly delayed decay of long-term potentiation. Therefore BMY 21502 was active in a physiological model that may predict of cognitive enhancement.

Different voltage-dependent thresholds for inducing long-term depression and long-term potentiation in slices of rat visual cortex

In the hippocampus and neocortex, high-frequency (tetanic) stimulation of an afferent pathway leads to long-term potentiation (LTP) of synaptic transmission. In the hippocampus it has recently been shown that long-term depression (LTD) of excitatory transmission can also be induced by certain combinations of synaptic activation. In most hippocampal and all neocortical pathways studied so far, the induction of LTP requires the activation of N-methyl-D-aspartate (NMDA) receptor-gated conductances. Here we report that LTD can occur in neurons of slices of the rat visual cortex and that the same tetanic stimulation can induce either LTP or LTD depending on the level of depolarization of the postsynaptic neuron. By applying intracellular current injections or pharmacological disinhibition to modify the depolarizing response of the postsynaptic neuron to tetanic stimulation, we show that the mechanisms of induction of LTD and LTP are both postsynaptic. LTD is obtained if postsynaptic depolarization exceeds a critical level but remains below a threshold related to NMDA receptor-gated conductances, whereas LTP is induced if this second threshold is reached.

Long-term potentiation in slices from subcortically deafferented hippocampi

Long-term potentiation (LTP) can be initiated in CA1, but not in the dentate, region of slices from rats with bilateral subcortical deafferentation at 8 week survival time. At about one week survival time, LTP is present in the CA1 region of all and also in the dentate of about 50% of slices. The results suggest that subcortical cholinergic and catecholaminergic inputs are not required for the LTP in the CA1 area of the rat hippocampus.

Facilitation of hippocampal long-term potentiation in slices perfused with high concentrations of calcium

The effect of increased extracellular calcium on long-term potentiation (LTP) of synaptic transmission has been examined in the CA1 region of guinea pig hippocampal slice preparation using extracellular recordings from the dendritic layer. The application of high calcium (4 mM) led to an increase in the initial slope of the field potential that reserved following return to control (2 mM calcium) solution. The magnitude of the field potential change was unaffected by prior induction of LTP, and inputs tetanized after return to control solution showed the same amount of LTP as those tetanized before the high calcium application. These results suggest that the calcium application by itself did not induce LTP. Inputs tetanized in the high calcium solution showed a greater amount of potentiation than in control solution, any given train producing about twice as much potentiation. However, using long trains (40 impulses) at high strength (2x test strength) gave similar LTP values in the two solutions. The facilitatory effect of high calcium on LTP was completely blocked by raising extracellular magnesium from 2 to 4 mM. As in control solution, LTP evoked in the high calcium solution was blocked by 2-amino-5-phosphono-valerate. The results support the view that calcium influx through postsynaptic N-methyl- d-aspartate receptor channels is directly involved in the induction of LTP.

Facilitated induction of hippocampal long-term potentiation in slices perfused with low concentrations of magnesium

The generation of long-term potentiation of synaptic transmission in area CA1 of hippocampal slices of the guinea-pig has been examined in solutions containing low concentrations of magnesium ions. It was found that the induction of long-term potentiation is greatly facilitated in slices perfused with 0.1 mM magnesium but much less so with 0.5 mM magnesium solution. The long-term potentiation evoked by brief tetanization in 0.1 mM magnesium was prevented following application of the N-methyl- d-aspartate receptor antagonist 2-amino-5-phosphonovalerate. Moreover, the response to tetanization, recorded in the dendritic layer, contained a much greater than normal component blocked by 2-amino-5-phosphonovalerate. The latter represents current through postsynaptic N-methyl- d-aspartate receptor channels, suggesting that the facilitation of long-term potentiation is related to a facilitated opening of these channels. The results support the notion that the generation of long-term potentiation is related to current through N-methyl- d-aspartate receptor channels which is under the control of extracellular magnesium ions.

Organization of visual pathways in normal and visually deprived cats.

Organization of visual pathways in normal and visually deprived cats.