Long-term Potentiation Of Synaptic Responses Research Articles

Contribution of histone acetylation to the serotonin-mediated long-term synaptic plasticity in terrestrial snails.

Serotonin plays a decisive role in long-term synaptic plasticity and long-term memory in mollusks. Previously, we demonstrated that histone acetylation is a regulatory mechanism of long-term memory in terrestrial snail. At the behavioral level, many studies were done in Helix to elucidate the role of histone acetylation and serotonin. However, the impact of histone acetylation on long-term potentiation of synaptic efficiency in electrophysiological studies in Helix has been studied only in one paper. Here we investigated effects of serotonin, histone deacetylases inhibitors sodium butyrate and trichostatin A, and a serotonergic receptor inhibitor methiothepin on long-term potentiation of synaptic responses in vitro. We demonstrated that methiothepin drastically declined the EPSPs amplitudes when long-term potentiation was induced, while co-application either of histone deacetylase inhibitors sodium butyrate or trichostatin A with methiothepin prevented the weakening of potentiation. We showed that single serotonin application in combination with histone deacetylase blockade could mimic the effect of repeated serotonin applications and be enough for sustained long-lasting synaptic changes. The data obtained demonstrated that histone deacetylases blockade ameliorated deficits in synaptic plasticity induced by different paradigms (methiothepin treatment, the weak training protocol with single application of serotonin), suggesting that histone acetylation contributes to the serotonin-mediated synaptic plasticity.

Ингибитор гистондеацитилаз усиливает долговременную синаптическую потенциацию в нейронах виноградной улитки

Recently, substantial amount of data was accumulated in the literature suggesting an important role of epigenetics in formation of long-term synaptic plasticity - the main cellular mechanism of learning and memory. In this work, we studied the effect of inhibition of histone deacetylases, one of the types of epigenetic modifications, on the formation of long-term potentiation of synaptic responses in premotor (command) neurons of the avoidance behavior of the grape snail. Potentiation of synaptic inputs in these neurons underlies aversive memory in this animal. We showed that histone deacetylase inhibitor sodium butyrate increases the amplitude of long-term potentiation caused by five tetanizations of the sensory nerve, combined with application of serotonin. We also found that application of sodium butyrate by itself caused an increase in EPSP amplitude 4 hours after application. However, this increase cannot underlie the observed effect of long-term potentiation, which was observed throughout the experiment. Thus, in our work, we have demonstrated the role of histone modifications in long-term changes in synaptic plasticity.

Heterosynaptic plasticity induced by intracellular tetanization in layer 2/3 pyramidal neurons in rat auditory cortex

Associative Hebbian-type synaptic plasticity underlies the mechanisms of learning and memory; however, Hebbian learning rules lead to runaway dynamics of synaptic weights and lack mechanisms for synaptic competition.Heterosynaptic plasticity may solve these problems by complementing plasticity at synapses that were active during the induction, with opposite-sign changes at non-activated synapses. In visual cortex, a potential candidate mechanism for normalization is plasticity induced by a purely postsynaptic protocol, intracellular tetanization. Here we asked if intracellular tetanization can induce long-term plasticity in auditory cortex. We recorded excitatory postsynaptic potentials (EPSPs) of regular (n =76) and all-or-none (n =24) type in layer 2/3 pyramidal cells in slices from rat auditory cortex. After intracellular tetanization, 32 of 76 regular inputs (42%) showed long-term depression, 21 inputs (28%) showed potentiation and 23 inputs (30%) did not change. The direction of plasticity correlated with the initial release probability: inputs with initially low release probability tended to be potentiated, while inputs with high release probability tended to be depressed. Thus, intracellular tetanization had a normalizing effect on synaptic efficacy. Induction of plasticity by intracellular tetanization required a rise of intracellular [Ca(2+)], because it was impaired by chelating intracellular calcium with EGTA. The long-term changes induced by intracellular tetanization involved both pre and postsynaptic mechanisms. EPSP amplitude changes were correlated with changes of release indices: paired-pulse ratio and the inverse of the coefficient of variation (CV(-2)). Furthermore at some all-or-none synapses, changes of averaged response amplitude were correlated with a change of the failure rate, without a change of the synaptic potency, measured as averaged amplitude of successful responses. Presynaptic components of plastic changes were abolished in experiments with blockade of NO-synthesis and spread, indicating involvement of NO signalling. These results demonstrate that the ability of purely postsynaptic challenges to induce plasticity is a general property of pyramidal neurons of both auditory and visual cortices.

Locus Ceruleus Activation Suppresses Feedforward Interneurons and Reduces β-γ Electroencephalogram Frequencies While It Enhances θ Frequencies in Rat Dentate Gyrus

The locus ceruleus is activated by novel stimuli, and its activation promotes learning and memory. Phasic activation of locus ceruleus neurons by glutamate enhances the dentate gyrus population spike amplitude and results in long-term potentiation of synaptic responses recorded after 24 h. Cholinergic activation of locus ceruleus neurons increases hippocampal . At the level of the cellular network, it is not clear how the potentiating effects of norepinephrine are mediated. Previous studies show that exogenous norepinephrine enhances inhibitory interneuron firing in the dentate gyrus. This finding appears at odds with evidence for potentiation. In this study, natural release of norepinephrine was induced by glutamate activation of locus ceruleus while we recorded EEGs and physiologically identified interneurons in the dentate gyrus of urethane-anesthetized rats. Feedforward neurons were inhibited (approximately 1-2 min) by locus ceruleus activation. Feedback interneurons showed both increased and decreased activity, whereas granule cells increased firing as predicted by evoked potential studies. EEG results replicated an increase in power (4-8 Hz) with locus ceruleus activation, but the effect with glutamatergic locus ceruleus activation was transient (approximately 1-2 min). Beta-gamma Frequencies were also transiently suppressed. Together, the data suggest that locus ceruleus activation enhances the throughput of concomitant sensory input by reducing feedforward inhibitory interneuron activity, which may reduce "binding" in existing cell assemblies, and enhances the conditions for synaptic plasticity through disinhibition, promotion of 4-8 Hz , and noradrenergic potentiation to facilitate the building of new representations.

Reversal of excitatory postsynaptic potential/spike potentiation in the CA1 area of the rat hippocampus

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- d-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.

Non-involvement of the redox site of NMDA receptors in bidirectional synaptic plasticity in the CA1 area of the rat hippocampus in vitro

We have examined the effects of the redox reagent 5,5′-dithiobis-2-nitrobenzoic acid (DTNB) on synaptic potentials recorded extracellularly from the CA1 area in hippocampal slices following low frequency stimulation (LFS) and tetanic stimulation (TS). Application of DTNB (200 μM) neither changed synaptic responses, nor prevented the expression of TS-induced long-term potentiation of synaptic responses and their depotentiation by LFS. Conversely, in naive slices, LFS still induced long-term depression of synaptic responses following application of DTNB. This depression could be subsequently reversed with a TS. It is concluded that the redox state of N-methyl- d-aspartate receptors does not affect the expression of long-term potentiation and depression of synaptic responses.

Long-term potentiation of synaptic responses in the rat dentate gyrus is due to increased quantal content

Long-term potentiation (LTP) of synaptic responses in the dentate gyrus neurons of the rat hippocampus was studied in in vitro slices with the use of intracellular recordings. The goal of the study was to determine if the expression of LTP is pre- or postsynaptic. LTP was induced by tetanic stimulation of the perforant pathway in the presence of bicuculline. The expression of potentiation was measured during low-intensity stimulation at 1–5 Hz. It was found that a 104% (S.E.M. ±35, n = 5) increase in the amplitude of evoked synaptic potentials was associated with a reduction in the number of transmission failures to 38% (S.E.M. ±15, n = 5) of the control values. The size of quantal responses was determined on the basis of asynchronous release from stimulated synapses. The average size of the quanta remained unchanged during LTP. The evident increase of quantal content suggests a presynaptic locus for expression of LTP.

A simple method for organotypic cultures of nervous tissue

Hippocampal slices prepared from 2–23-day-old neonates were maintained in culture at the interface between air and a culture medium. They were placed on a sterile, transparent and porous membrane and kept in petri dishes in an incubator. No plasma clot or roller drum were used. This method yields thin slices which remain 1–4 cell layers thick and are characterized by a well preserved organotypic organization. Pyramidal neurons labelled by extra- and intracellular application of horse radish peroxidase resemble by the organization and complexity of their dendritic processes those observed in situ at a comparable developmental stage. Excitatory and inhibitory synaptic potentials can easily be analysed using extra- or intracellular recording techniques. After a few days in culture, long-term potentiation of synaptic responses can reproducibly be induced. Evidence for a sprouting response during the first days in culture or following sections is illustrated. This technique may represent an interesting alternative to roller tube cultures for studies of the developmental changes occurring during the first days or weeks in culture.

Chronic administration of a thiol-proteinase inhibitor blocks long-term potentiation of synaptic responses

It has been proposed that activation of a calcium-sensitive protease (calpain) is a crucial step in the induction of long-term potentiation (LTP). To test this hypothesis, we used chronic recording techniques to measure the effects of intraventricular infusion of leupeptin, a calpain inhibitor, on LTP in the hippocampus. Rats implanted bilaterally with stimulating electrodes in the Schaffer-commissural system and one recording electrode in the apical dentrites of field CA1 were fitted with osmotic mini-pumps delivering either leupeptin (20 mg/ml) or saline at a rate of 0.5 μl/h into the lateral ventricle. Short bursts of high-frequency stimulation with the bursts delivered at 5/s were used to induce LTP in those animals which had stable responses for several days. Rats in the saline group ( n = 11) exhibited an immediate LTP effect that remained in place over successive days of testing, while only 3 of 13 leupeptin treated animals showed evidence of LTP 24 h after high-frequency stimulation, and in only one of those was a sizeable effect recorded over several days. The average change in responses at the 24-h test point was +33% for the controls and +4% for the leupeptin group ( P < 0.01). The block of LTP induction was reversible, since high-frequency stimulation applied after disconnecting the pumps led to a robust LTP effect that lasted for several days in 6 of 7 animals tested. There were no detectable differences in baseline responses in the presence and absence of leupeptin.

Cooperativity among afferents for the induction of long-term potentiation in the CA1 region of the hippocampus

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.