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PubMed2002

Neocortical long-term potentiation and long-term depression: site of expression investigated by infrared-guided laser stimulation.

The synaptic site of expression of long-term potentiation (LTP) and long-term depression (LTD) is still a matter of debate. To address the question of presynaptic versus postsynaptic expression of neocortical LTP and LTD in a direct approach, we measured the glutamate sensitivity of apical dendrites of layer 5 pyramidal neurons during LTP and LTD. We used infrared-guided laser stimulation to release glutamate from its "caged" form with high spatial and temporal resolution. Responses to photolytically released glutamate and synaptically evoked EPSPs were recorded with patch-clamp pipettes from the neuronal somata. LTP and LTD could be induced by electrical stimulation at the same synapses in succession. The NMDA receptor-dependent LTD was accompanied by a decrease in the dendritic glutamate sensitivity, suggesting a postsynaptic expression of neocortical LTD. In contrast, LTP was never accompanied by a change in the dendritic glutamate sensitivity. A possible explanation for this finding is a presynaptic expression of neocortical LTP. Another set of experiments corroborated these results: Photolytic application of glutamate with a frequency of 5 Hz caused a long-lasting Ca2+ and NMDA receptor-dependent decrease in the dendritic glutamate sensitivity. In contrast, LTP of dendritic glutamate sensitivity was never induced by photostimulation, despite several experimental modifications to prevent washout of the induction mechanism and to induce a stronger postsynaptic Ca2+ influx. In conclusion, our findings provide strong evidence for a postsynaptic expression of neocortical LTD and favor a primarily presynaptic locus of neocortical LTP.

Animals↗
PubMed1997

Long-term potentiation and long-term depression are induced through pharmacologically distinct NMDA receptors.

N-Methyl-D-aspartate (NMDA) receptor activation initiates both homosynaptic long-term depression (LTD) and long-term potentiation (LTP) in the CA1 region of the hippocampus. The mechanism by which two opposing forms of synaptic plasticity can be initiated through the activation of a single receptor is not known. We examined the effects of two competitive antagonists on the induction of LTP and LTD, D-2-amino-5-phosphonovaleric acid (D-AP5), a broad spectrum inhibitor of the NMDA receptor, and 3-((RS)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), an antagonist that binds with high affinity to conventional NMDA receptors subtypes, but not to atypical subtypes that are relatively independent of voltage-dependent Mg2+-blockade. As has previously been reported, LTP, LTD, and depotentiation were all blocked by applications of D-AP5. In contrast, only LTP, but not LTD or depotentiation, was blocked by CPP. These observations suggest that decreases and increases of synaptic strength are mediated by the activation of distinct NMDA receptor subpopulations.

2-Amino-5-phosphonovalerate↗
PubMed1999

Prior short-term synaptic disinhibition facilitates long-term potentiation and suppresses long-term depression at CA1 hippocampal synapses.

Long-term potentiation (LTP) and long-term depression (LTD) are two main forms of activity-dependent synaptic plasticity that have been extensively studied as the putative mechanisms underlying learning and memory. Current studies have demonstrated that prior synaptic activity can influence the subsequent induction of LTP and LTD at Schaffer collateral-CA1 synapses. Here, we show that prior short-term synaptic disinhibition induced by type A gamma-aminobutyric acid (GABA) receptor antagonist picrotoxin exhibited a facilitation of LTP induction and an inhibition of LTD induction. This effect lasted between 10 and 30 min after washout of picrotoxin and was specifically inhibited by the L-type voltage-operated Ca2+ channel (VOCC) blocker nimodipine, but not by the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphopentanoic acid (D-APV). Moreover, this picrotoxin-induced priming effect was mimicked by forskolin, an activator of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), and was blocked by the adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22536) and the PKA inhibitor Rp-adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS). It was also found that following picrotoxin application, CA1 neurons have a higher probability of synchronous discharge in response to a population of excitatory postsynaptic potential (EPSP) of fixed slope (EPSP/spike potentiation). However, picrotoxin treatment did not significantly affect paired-pulse facilitation (PPF). These findings suggest that a brief of GABAergic disinhibition can act as a priming stimulus for the subsequent induction of LTP and LTD at Schaffer collateral-CA1 synapses. The increase in Ca2+ influx through L-type VOCCs in turn triggering a cAMP/PKA signalling pathway is a possible molecular mechanism underlying this priming effect.

Adenine↗
PubMed2002

Long-term depression and long-term potentiation in horizontal connections of the barrel cortex.

Synaptic plasticity of horizontally orientated connections between barrels, in the barrel cortex of adult mice, was studied in slice preparations cut across rows of barrels. Field potentials were evoked in the middle of one barrel column (in layer IV or V) and recorded in the neighbouring barrel (in layer IV and V). In layer IV, long-term depression (LTD) by 26.5 +/- 5% was first induced by a low-frequency stimulation (2 Hz) applied for 10 min. After 30 min, theta-burst stimulation was delivered to previously depressed connections, resulting in long-term potentiation (LTP) by 28.8 +/- 11.8%. When theta-burst stimulation was delivered without an earlier low-frequency stimulation, no LTP was induced. Similar results were obtained in layer V connections (LTD: 40.6 +/- 12.5%; LTP: 26.9 +/- 12.5%). In layer IV, the application of 100 micro m d,l-2-amino-5-phosphonovaleric acid (APV), an antagonist of NMDA receptors, blocked the induction of both LTD and LTP. These experiments show that a potential for synaptic plasticity is retained in granular and infragranular layers of adult mice.

Animals↗
PubMed1994

Developmental shift from long-term depression to long-term potentiation at the mossy fibre synapses in the rat hippocampus.

During development, in the CA1 hippocampal region, long-term potentiation (LTP) starts appearing at postnatal (P) day 7 and reaches its maximal expression towards the end of the second postnatal week. However, LTP is often preceded by long-term depression (LTD), an activity-dependent and long-lasting reduction of synaptic strength. LTD can be induced by sustained, low-frequency stimulation of the afferent pathway and is dependent on activation of N-methyl-D-aspartate (NMDA) receptors. We report here that, in the CA3 hippocampal region, during a critical period of postnatal development, between P6 and P14, a high-frequency stimulation train (100 Hz, 1 s) to the mossy fibres in the presence of the NMDA receptor antagonist (+)-3-(2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid (CPP; 20 microM) induced LTD. The depression of the amplitude of the field excitatory postsynaptic potential (EPSP) was 28 +/- 7% (n = 21). This form of LTD was NMDA-independent and synapse-specific. When a tetanus was applied in the presence of CPP and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 microM), which blocked the field EPSP, it failed to induce LTD upon washout of CNQX. LTD was probably postsynaptic in origin since it did not affect paired-pulse facilitation. A rise in extracellular calcium concentration (from 2 to 4 mM) produced LTP instead of LTD. At the end of the second postnatal week, the same high-frequency stimulation train to the mossy fibres induced LTP as in adult neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Developmental shift from long-term depression to long-term potentiation in the rat medial vestibular nuclei: role of group I metabotropic glutamate receptors.

The effects of high frequency stimulation (HFS) of the primary vestibular afferents on synaptic transmission in the ventral part of the medial vestibular nuclei (vMVN) were studied during postnatal development and compared with the changes in the expression of the group I metabotropic glutamate receptor (mGluR) subtypes, mGluR1 and mGluR5. During the first stages of development, HFS always induced a mGluR5- and GABAA-dependent long-term depression (LTD) which did not require NMDA receptor and mGluR1 activation. The probability of inducing LTD decreased progressively throughout the development and it was zero at about the end of the second postnatal week. Conversely, long-term potentiation (LTP) appeared at the beginning of the second week and its occurrence increased to reach the adult value at the end of the third week. Of interest, the sudden change in the LTP frequency occurred at the time of eye opening, about the end of the second postnatal week. LTP depended on NMDA receptor and mGluR1 activation. In parallel with the modifications in synaptic plasticity, we observed that the expression patterns and localizations of mGluR5 and mGluR1 in the medial vestibular nuclei (MVN) changed during postnatal development. At the earlier stages the mGluR1 expression was minimal, then increased progressively. In contrast, mGluR5 expression was initially high, then decreased. While mGluR1 was exclusively localized in neuronal compartments and concentrated at the postsynaptic sites at all stages observed, mGluR5 was found mainly in neuronal compartments at immature stages, then preferentially in glial compartments at mature stages. These results provide the first evidence for a progressive change from LTD to LTP accompanied by a distinct maturation expression of mGluR1 and mGluR5 during the development of the MVN.

2-Amino-5-phosphonovalerate↗
PubMed1994

Neural analogue of long-term sensitization training produces long-term (24 and 48 h) facilitation of the sensory-to-motor neuron connection in Aplysia.

1. An in vitro analogue of long-term sensitization training was used to gain insights into the mechanisms and time course of the memory for long-term sensitization in Aplysia. The analogue, consisting of four blocks of shocks, was delivered to peripheral nerves of the isolated pleural-pedal ganglia, which contain the sensory neurons and motor neurons that mediate the tail withdrawal reflex. 2. Long-term facilitation of the connections between the sensory neurons and motor neurons was produced by the conjoint stimulation of two peripheral nerves, P8 and P9. Long-term facilitation, however, was not observed after conjoint stimulation of three nerves, P7, P8, and P9. 3. The preparation was viable and stable (no changes in the amplitudes of excitatory postsynaptic potentials (EPSPs) and membrane properties in controls) for at least 48 h. Moreover, the long-term facilitation persisted for at least 48 h. 4. We observed no significant long-term changes in the resting membrane potentials of the sensory and motor neurons or in the input resistance of the motor neurons 24 and 48 h after the conjoint stimulation of nerves P8 and P9. Thus changes in these biophysical properties do not appear to contribute to the expression of long-term facilitation. 5. The finding that conjoint stimulation of three nerves, P7, P8, and P9, produced no long-term facilitation raised the possibility that stimulation of nerve P7 alone might produce long-term inhibition that opposes the facilitatory effects induced by conjoint stimulation of nerves P8 and P9. Stimulation of nerve P7 alone, however, had no long-term inhibitory effect on the EPSPs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Dopamine and cAMP-regulated phosphoprotein 32 kDa controls both striatal long-term depression and long-term potentiation, opposing forms of synaptic plasticity.

A complex chain of intracellular signaling events, critically important in motor control, is activated by the stimulation of D1-like dopamine (DA) receptors in striatal neurons. At corticostriatal synapses on medium spiny neurons, we provide evidence that the D1-like receptor-dependent activation of DA and cyclic adenosine 3',5' monophosphate-regulated phosphoprotein 32 kDa is a crucial step for the induction of both long-term depression (LTD) and long-term potentiation (LTP), two opposing forms of synaptic plasticity. In addition, formation of LTD and LTP requires the activation of protein kinase G and protein kinase A, respectively, in striatal projection neurons. These kinases appear to be stimulated by the activation of D1-like receptors in distinct neuronal populations.

Action Potentials↗
PubMed2003

Long-term potentiation and long-term depression induced by local application of ATP to hippocampal CA1 neurons of the guinea pig.

The present study has investigated the role of ATP in the induction of synaptic plasticity, using local application of ATP by picopump administration into the stratum radiatum of guinea pig hippocampal region CA1. Excitatory postsynaptic currents (EPSCs) evoked by stimulation of Schaffer collateral/commissural afferents synapsing on CA1 pyramidal cells of hippocampal slices were monitored in voltage-clamp mode, using whole-cell recording. Brief local application of ATP (1 mM) induced an inward current, usually consisting of early- and late-phase components. Because the late-phase component of an ATP-induced current was largely inhibited by Ca2+-free solution, this component is supposed to depend on extracellular Ca2+. After local application of ATP, long-term synaptic modification of EPSCs was induced: LTP was detected in neurons exhibiting a small late Ca2+ current, while LTD was obtained from recordings showing a large late Ca2+ current in response to ATP application. There was a statistically significant correlation between the magnitude of long-term plastic changes and the size of Ca2+ currents in response to ATP application. Furthermore, there was significant difference between the average size of the Ca2+ current in the LTP group and the size in the LTD group. These results suggest that a small Ca2+ influx in response to ATP application induces LTP, whereas a large one induces LTD in guinea pig hippocampal CA1 neurons.

Adenosine Triphosphate↗
PubMed1993

Long-term potentiation and long-term depression of primary afferent neurotransmission in the rat spinal cord.

Synaptic transmission between dorsal root afferents and neurons in the superficial laminae of the spinal dorsal horn (laminae I-III) was examined by intracellular recording in a transverse slice preparation of rat spinal cord. Brief high-frequency electrical stimulation (300 pulses at 100 Hz) of primary afferent fibers produced a long-term potentiation (LTP) or a long-term depression (LTD) of fast (monosynaptic and polysynaptic) EPSPs in a high proportion of dorsal horn neurons. Both the AMPA and the NMDA receptor-mediated components of synaptic transmission at the primary afferent synapses with neurons in the dorsal horn can exhibit LTP and LTD of the synaptic responses. In normal and neonatally capsaicin-treated rats, the induction of LTP requires the activation of NMDA receptor-gated conductances. The induction of LTP or LTD, however, was not abolished in the presence of bicuculline, a GABAA receptor antagonist. The results demonstrate that distinct and long-lasting modulation in synaptic efficiency can be induced at primary afferent synapses with neurons in the superficial laminae of spinal dorsal horn by high-frequency stimulation of dorsal root afferents and that these changes may be physiologically relevant for transmission and integration of sensory information, including pain.

Animals↗
PubMed2001

Gamma-aminobutyric acid type A receptors modulate cAMP-mediated long-term potentiation and long-term depression at monosynaptic CA3-CA1 synapses.

cAMP induces a protein-synthesis-dependent late phase of long-term potentiation (LTP) at CA3-CA1 synapses in acute hippocampal slices. Herein we report cAMP-mediated LTP and long-term depression (LTD) at monosynaptic CA3-CA1 cell pairs in organotypic hippocampal slice cultures. After bath application of the membrane-permeable cAMP analog adenosine 3',5'-cyclic monophosphorothioate, Sp isomer (Sp-cAMPS), synaptic transmission was enhanced for at least 2 h. Consistent with previous findings, the late phase of LTP requires activation of cAMP-dependent protein kinase A and protein synthesis. There is also an early phase of LTP induced by cAMP; the early phase depends on protein kinase A but, in contrast to the later phase, does not require protein synthesis. In addition, the cAMP-induced LTP is associated with a reduction of paired-pulse facilitation, suggesting that presynaptic modification may be involved. Furthermore, we found that Sp-cAMPS induced LTD in slices pretreated with picrotoxin, a gamma-aminobutyric acid type A (GABA(A)) receptor antagonist. This form of LTD depends on protein synthesis and protein phosphatase(s) and is accompanied by an increased ratio of failed synaptic transmission. These results suggest that GABA(A) receptors can modulate the effect of cAMP on synaptic transmission and thus determine the direction of synaptic plasticity.

Animals↗
PubMed1996

Long-term potentiation and long-term depression of horizontal connections in rat motor cortex.

This paper reviews studies that investigate conditions resulting in long-lasting modifications of synaptic efficacy in horizontal connections within layers II/III of adult rat motor cortex using the in vitro slice preparation. Long-term potentiation (LTP) was induced by high frequency theta burst stimulation (TBS) when local synaptic inhibition was transiently suppressed by bicuculline methiodide application at the recording site immediately prior to TBS of the horizontal pathway. Without bicuculline, TBS failed to produce LTP. LTP could also be induced without Bic application by conjoint TBS of horizontal and vertical (ascending) inputs. By contrast, long-term depression (LTD) of horizontal transmission was induced by 10 min of 2 Hz stimulation. Depressed horizontal connections nevertheless retained the capability for synaptic strength increases. These studies indicate that synaptic modification across horizontally connected neurones is regulated both by the arrangement of their intrinsic circuits and by the availability of mechanisms for modification at individual synapses. Activity dependent forms of synaptic plasticity operating within horizontal connections may form a spatial substrate and mechanism for experience-dependent regulation of cortical representations.

Animals↗
PubMed1983

An inhalation method for testing the toxicity of volatile compounds in small laboratory animals. A study on short-term and long-term toluene inhalation in rats.

A coupola-shaped Plexiglass inhalation chamber (volume 190 I) with continuous infusion of toxicant and air flow was constructed for small laboratory animals. The method guarantees an even distribution of vapourized toxicant to 16 animals at the same time, and is convenient both in short-term and long-term experiments. As a volatile toxicant, toluene was used. The short-term and long-term effects of toluence on rats were studied using psychomotor tests, blood glucose, serum ALAT and ASAT values as well as hematocrit. Short-term exposure, but not long-term, impaired the performance in psychomotor tests, elevated blood glucose and serum ALAT and ASAT levels, and slightly increased hematocrit. Body weight decreased as compared to controls in short-term toluene exposure, but showed no difference in long-term treatment between toluene-and control groups at the end of exposure. The differences between the two exposures are probably due to the development of tolerance during long-term exposure either on receptor or metabolic level.

Alanine Transaminase↗
PubMed1996

Involvement of silent synapses in the induction of long-term potentiation and long-term depression in neocortical and hippocampal neurons.

Changes in the latency of small excitatory postsynaptic potentials were observed in association with induction of long-term modifications of synaptic transmission in slices of rat neocortex and guinea-pig hippocampus. After potentiation response latency decreased in 3/10 cases in the neocortex and in 6/24 cases in the hippocampus, and increased after depression in 4/8 cases in the neocortex. These latency changes could not be attributed to changes in presynaptic fibre excitability, monosynaptic inhibition, release kinetics or activation kinetics of postsynaptic ion channels. We conclude therefore that potentiation led to the activation of previously silent synapses of fast-conducting afferents and depression to the inactivation of previously functional synapses. Thus, neocortical and hippocampal synapses can be in a non-functional state, and regimes that induce long-term potentiation and depression not only change the efficacy of synapses but also alter their functional state.

Animals↗
PubMed2006

Interlaboratory evaluation of Hyalella azteca and Chironomus tentans short-term and long-term sediment toxicity tests.

Methods for assessing the long-term toxicity of sediments to Hyalella azteca and Chironomus tentans can significantly enhance the capacity to assess sublethal effects of contaminated sediments through multiple endpoints. Sublethal tests allow us to begin to understand the relationship between short-term and long-term effects for toxic sediments. We present an interlaboratory evaluation with long-term and 10-d tests using control and contaminated sediments in which we assess whether proposed and existing performance criteria (test acceptability criteria [TAC]) could be achieved. Laboratories became familiar with newly developed, long-term protocols by testing two control sediments in phase 1. In phase 2, the 10-d and long-term tests were examined with several sediments. Laboratories met the TACs, but results varied depending on the test organism, test duration, and endpoints. For the long-term tests in phase 1, 66 to 100% of the laboratories consistently met the TACs for survival, growth, or reproduction using H. azrteca, and 70 to 100% of the laboratories met the TACs for survival and growth, emergence, reproduction, and hatchability using C. tentans. In phase 2, fewer laboratories participated in long-term tests: 71 to 88% of the laboratories met the TAC for H. azteca, whereas 50 to 67% met the TAC for C. tentans. In the 10-d tests with H. azteca and C. tentans, 82 and 88% of the laboratories met the TAC for survival, respectively, and 80% met the TAC for C. tentans growth. For the 10-d and long-term tests, laboratories predicted similar toxicity. Overall, the interlaboratory evaluation showed good precision of the methods, appropriate endpoints were incorporated into the test protocols, and tests effectively predicted the toxicity of sediments.

Animals↗