Showing papers on "Long-term potentiation published in 1994"
TL;DR: Consistent with models claiming a role for long-term potentiation (LTP) in memory, LTP in hippocampal slices from CREB mutants decayed to baseline 90 min after tetanic stimulation, however, paired-pulse facilitation and posttetanic potentiation are normal.
1,832 citations
TL;DR: Direct evidence is presented that NMDA receptors exist in rat neocortex as heteromeric complexes of considerable heterogeneity, some containing both NR2A and NR2B subunits.
Abstract: ACTIVATION of the N-methyl-d-aspartate (NMDA) receptor is important for certain forms of activity-dependent synaptic plasticity, such as long-term potentiation (reviewed in ref. 1), and the patterning of connections during development of the visual system (reviewed in refs 2, 3). Several subunits of the NMDA receptor have been cloned: these are NMDAR1 (NR1), and NMDAR2A, 2B, 2C and 2D (NR2A-D)4–8. Based on heterologous co-expression studies, it is inferred that NR1 encodes an essential subunit of NMDA receptors and that functional diversity of NMDA receptors in vivo is effected by differential incorporation of subunits NR2A–NR2D5–8. Little is known, however, about the actual subunit composition or heterogeneity of NMDA receptors in the brain. By co-immunoprecipitation with subunit-specific antibodies, we present here direct evidence that NMDA receptors exist in rat neocortex as heteromeric complexes of considerable heterogeneity, some containing both NR2A and NR2B subunits. A progressive alteration in subunit composition seen postnatally could contribute to NMDA-receptor variation and changing synaptic plasticity during cortical development.
1,328 citations
TL;DR: A new form of synaptic plasticity, homosynaptic long-term depression (LTD) has also recently been documented, which, like LTP, requires Ca2+ entry through the NMDA receptor, and current work suggests that this LTD is a reversal ofLTP, and that the mechanisms of LTP and LTD may converge at the level of specific phosphoproteins.
1,300 citations
TL;DR: A signalling pathway in which calcineurin dephosphorylates and inactivates inhibitor-1 increases PP1 activity and contributes to the generation of LTD, which is suggested to be an activity-dependent decrease in synaptic efficacy.
Abstract: Long-term potentiation (LTP) is a synaptic mechanism thought to be involved in learning and memory Long-term depression (LTD), an activity-dependent decrease in synaptic efficacy, may be an equally important mechanism which permits neural networks to store information more effectively One form of LTD that has been observed in the hippocampus requires activation of postsynaptic NMDA (N-methyl-D-aspartate) receptors, a change in postsynaptic calcium concentration, and activation of postsynaptic serine/threonine protein phosphatase 1 (PP1) or 2A (PP2A) The mechanism by which PP1 or PP2A is regulated by synaptic activity is unclear because these protein phosphatases are not directly influenced by calcium concentration LTD induction may require activation of a more complex protein phosphatase cascade consisting of the Ca2+/calmodulin-dependent protein phosphatase, calcineurin, its phosphoprotein substrate, inhibitor-1, and PP1 We tested this hypothesis using calcineurin inhibitors as well as different forms of inhibitor-1 loaded into postsynaptic cells Our results suggest a signalling pathway in which calcineurin dephosphorylates and inactivates inhibitor-1 This in turn increases PP1 activity and contributes to the generation of LTD
1,063 citations
TL;DR: It was found that the induction of L-LTP was selectively prevented when transcription was blocked immediately after tetanization or during application of cAMP, suggesting that the late phase of LTP in the CA1 region requires transcription during a critical period.
Abstract: Repeated high-frequency trains of stimuli induce long-term potentiation (LTP) in the CA1 region that persists for up to 8 hours in hippocampal slices and for days in intact animals. This long time course has made LTP an attractive model for certain forms of long-term memory in the mammalian brain. A hallmark of long-term memory in the intact animal is a requirement for transcription, and thus whether the late phase of LTP (L-LTP) requires transcription was investigated here. With the use of different inhibitors, it was found in rat hippocampal slices that the induction of L-LTP [produced either by tetanic stimulation or by application of the cyclic adenosine monophosphate (cAMP) analog Sp-cAMPS (Sp-cyclic adenosine 3',5'-monophosphorothioate)] was selectively prevented when transcription was blocked immediately after tetanization or during application of cAMP. As with behavioral memory, this requirement for transcription had a critical time window. Thus, the late phase of LTP in the CA1 region requires transcription during a critical period, perhaps because cAMP-inducible genes must be expressed during this period.
905 citations
TL;DR: This analysis is focused on the feedforward pathways from the entorhinal cortex to the dentate gyrus (DG) and region CA3 and finds that Hebbian synaptic modification facilitates completion but reduces separation, unless the strengths of synapses from inactive presynaptic units to active postsynaptic units are reduced (LTD).
Abstract: The hippocampus and related structures are thought to be capable of 1) representing cortical activity in a way that minimizes overlap of the representations assigned to different cortical patterns (pattern separation); and 2) modifying synaptic connections so that these representations can later be reinstated from partial or noisy versions of the cortical activity pattern that was present at the time of storage (pattern completion). We point out that there is a trade-off between pattern separation and completion and propose that the unique anatomical and physiological properties of the hippocampus might serve to minimize this trade-off. We use analytical methods to determine quantitative estimates of both separation and completion for specified parameterized models of the hippocampus. These estimates are then used to evaluate the role of various properties and of the hippocampus, such as the activity levels seen in different hippocampal regions, synaptic potentiation and depression, the multi-layer connectivity of the system, and the relatively focused and strong mossy fiber projections. This analysis is focused on the feedforward pathways from the entorhinal cortex (EC) to the dentate gyrus (DG) and region CA3. Among our results are the following: 1) Hebbian synaptic modification (LTP) facilitates completion but reduces separation, unless the strengths of synapses from inactive presynaptic units to active postsynaptic units are reduced (LTD). 2) Multiple layers, as in EC to DG to CA3, allow the compounding of pattern separation, but not pattern completion. 3) The variance of the input signal carried by the mossy fibers is important for separation, not the raw strength, which may explain why the mossy fiber inputs are few and relatively strong, rather than many and relatively weak like the other hippocampal pathways. 4) The EC projects to CA3 both directly and indirectly via the DG, which suggests that the two-stage pathway may dominate during pattern separation and the one-stage pathway may dominate during completion; methods the hippocampus may use to enhance this effect are discussed.
856 citations
TL;DR: It is argued that loss of function of PrPc may contribute to the early synaptic loss3 and neuronal degeneration seen in Creutzfeldt–Jakob disease and scrapie and bovine spongiform encephalopathy in animals.
Abstract: THE prion diseases are neurodegenerative conditions, transmissible by inoculation, and in some cases inherited as an autosomal dominant disorder. They include Creutzfeldt–Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. The prion consists principally of a post-translationally modified form of a host-encoded glycoprotein (PrPc), designated PrPSc (ref. 1); the normal cellular function of PrPc is, however, unknown. Although PrP is highly conserved among mammals and widely expressed in early embryogenesis, mice homozygous for disrupted PrP genes appear developmentally and behaviourally normal2. PrP is a protein anchored to the neuronal surface by glycosylphosphatidylinositol, suggesting a role in cell signalling or adhesion. Here we report that hippocampal slices from PrP null mice have weakened GABAA (γ-aminobutyric acid type A) receptor-mediated fast inhibition and impaired long-term potentiation. This impaired synaptic inhibition may be involved in the epileptiform activity seen in Creutzfeldt–Jakob disease and we argue that loss of function of PrPc may contribute to the early synaptic loss3 and neuronal degeneration seen in these diseases.
803 citations
TL;DR: The free radical gas nitric oxide is a recently identified neuronal messenger that carries out diverse signaling tasks in both the central and peripheral nervous systems and can bypass normal signal transduction routes involving interactions with synaptic membrane receptors.
Abstract: The free radical gas nitric oxide (NO) is a recently identified neuronal messenger that carries out diverse signaling tasks in both the central and peripheral nervous systems. Whereas most neurotransmitters are packaged in synaptic vesicles and secreted in a Ca2+-dependent manner from specialized nerve endings, NO is an unconventional transmitter which is not packaged in vesicles, but rather diffuses from its site of production in the absence of any specialized release machinery. The lack of a requirement for release apparatus raises the possibility that NO can be released from both pre- and postsynaptic neuronal elements. In addition, because NO is gaseous and extremely membrane permeant, it can bypass normal signal transduction routes involving interactions with synaptic membrane receptors. Although the targets of NO have not yet been completely described, it is known that NO can bind to the iron contained in heine groups, leading to conformational changes in associated proteins, such as guanylyl cyclase.
799 citations
TL;DR: Mice deficient in mGluRl have severe motor coordination and spatial learning deficits, and show impaired cerebellar long-term depression and hippocampal mossy fibre long- term potentiation, and should be valuable models for studying synaptic plasticity.
Abstract: Metabotropic glutamate receptor 1 (mGluR1) is a member of a large family of G-protein-coupled glutamate receptors, the physiological functions of which are largely unknown. Mice deficient in mGluR1 have severe motor coordination and spatial learning deficits. They have no gross anatomical or basic electrophysiological abnormalities in either the cerebellum or hippocampus, but they show impaired cerebellar long-term depression and hippocampal mossy fibre long-term potentiation. mGluR1-deficient mice should therefore be valuable models for studying synaptic plasticity.
739 citations
TL;DR: This minireview will provide an update on the cellular mechanisms of LTP and distinguish those mechanisms that are firmly established from those that remain contentious.
672 citations
TL;DR: It is proposed that mGluR1 is not "in line" in LTP production, but rather modulates the plasticity process, and hence affects context-specific associative learning.
TL;DR: It is proposed that calcium entry into the presynaptic terminal may activate Ca(2+)-calmodulin-sensitive adenylyl cyclase I which, through protein kinase A, causes a persistent enhancement of evoked glutamate release.
Abstract: Repetitive activation of hippocampal mossy fibers evokes a long-term potentiation (LTP) of synaptic responses in pyramidal cells in the CA3 region that is independent of N-methyl-D-aspartate receptor activation. Previous results suggest that the site for both the induction and expression of this form of LTP is presynaptic. Experimental elevation of cyclic adenosine 3',5'-monophosphate (cAMP) both mimics and interferes with tetanus-induced mossy fiber LTP, and blockers of the cAMP cascade block mossy fiber LTP. It is proposed that calcium entry into the presynaptic terminal may activate Ca(2+)-calmodulin-sensitive adenylyl cyclase I which, through protein kinase A, causes a persistent enhancement of evoked glutamate release.
TL;DR: It is suggested that L1 and NCAM modulate the develop-ment or the stabilization of LTP, a sustained-use-dependent increase in synaptic efficacy that has been impli-cated in learning and memory.
Abstract: Synaptic membranes express cell adhesion molecules. Here we investigate the role of the neural cell adhesion molecules L1 and NCAM in hippocampal long-term potentiation (LTP), a sustained-use-dependent increase in synaptic efficacy that has been implicated in learning and memory. L1 and NCAM mediate cell interactions during neural development and are strongly expressed in the hippocampus. They cooperate to strengthen L1-dependent cell adhesion and are coupled to second messenger pathways. We show that LTP in CA1 neurons of rat hippocampal slices was reduced by application of various L1 and NCAM antibodies, recombinant L1 fragments, and upon dissociation of the L1/NCAM complex through oligomannosidic carbohydrates and NCAM peptides. Neither the activation of NMDA (N-methyl-D-aspartate) receptors nor the maintenance of LTP was affected. These results suggest that L1 and NCAM modulate the development or the stabilization of LTP.
TL;DR: Experiments show that activity of CaM kinase II is increased for long periods of time after induction of long-term potentiation, that enhanced activity mimics long- term potentiated activity, and that enzyme activity is necessary for induction ofLong-Term potentiation.
TL;DR: It is found that mossy Fiber LTP also has phases, and although Schaffer collateral and mossy fiber pathways use very different mechanisms for early phase, both use a cAMP-mediated mechanism for late phase.
TL;DR: Results suggest that NO production and its extracellular movement may be links in the pathway from NMDA receptor activation to changes in chemical signaling in surrounding synaptic terminals in the cerebral cortex.
Abstract: L-Glutamate and norepinephrine are examples of a major excitatory neurotransmitter and a neuromodulator in the cerebral cortex, respectively. Little is known of how chemical signaling between the anatomically distinct chemical pathways occurs. Specific activation of the N-methyl-D-aspartate (NMDA) class of glutamate receptor in synaptosomal preparations from guinea pig cerebral cortex caused release of both of these chemicals, and this release was blocked by agents that inhibit nitric oxide (NO) production or remove NO from the extracellular space. Furthermore, neurotransmitter release correlated with cortical NO production after NMDA receptor stimulation. These results suggest that NO production and its extracellular movement may be links in the pathway from NMDA receptor activation to changes in chemical signaling in surrounding synaptic terminals in the cerebral cortex.
TL;DR: The results indicate that the two mechanistically distinctive forms of LTP, a transient, early component (E-LTP) and a more enduring form (L- LTP), can be recruited selectively by changing the number of conditioning tetanic trains.
Abstract: To study how the late phase of long-term potentiation (LTP) in hippocampus arises, we examined the resulting LTP for its time course and its dependence on protein synthesis and different second-messenger kinases by applying various conditioning tetani. We find that one high-frequency train (100 Hz) produces a form of LTP that lasts longer than 1 hr but less than 3 hr (the early phase of LTP, or E-LTP). It is blocked by inhibitors of calcium/calmodulin kinase II (Cam kinase II) but is not affected by an inhibitor of cAMP-dependent protein kinase [protein kinase A (PKA) and the protein synthesis inhibitor anisomycin] nor is it occluded by the cAMP activator forskolin. In contrast, when three high-frequency trains are used, the resulting potentiation persists for at least 6-10 hr. The L-LTP induced by three trains differs from the E-LTP in that it requires new protein synthesis, is blocked by an inhibitor of cAMP-dependent protein kinase, and is occluded by forskolin. These results indicate that the two mechanistically distinctive forms of LTP, a transient, early component (E-LTP) and a more enduring form (L-LTP), can be recruited selectively by changing the number of conditioning tetanic trains. Repeated tetani induce a PKA and protein synthesis-dependent late component that adds to the amplitude and duration of the potentiation induced by a single tetanus.
TL;DR: The induction of LTD in hippocampal CA1 pyramidal neurons in neonatal rats is shown to depend on postsynaptic calcium ion entry through L-type voltage-gated calcium channels paired with the activation of metabotropic glutamate receptors, suggesting that LTD is likely to require the production of a retrograde messenger.
Abstract: Long-term depression (LTD) is an activity-dependent decrease in synaptic efficacy that together with its counterpart, long-term potentiation, is thought to be an important cellular mechanism for learning and memory in the mammalian brain. The induction of LTD in hippocampal CA1 pyramidal neurons in neonatal rats is shown to depend on postsynaptic calcium ion entry through L-type voltage-gated calcium channels paired with the activation of metabotropic glutamate receptors. Although induced postsynaptically, LTD is due to a long-term decrease in transmitter release from presynaptic terminals. This suggests that LTD is likely to require the production of a retrograde messenger.
TL;DR: This review shall examine the opposite phenomenon, use-dependent decreases in synaptic strength, or long-term depression, which is a broad term that is used to describe synaptic depression according to several different learning rules and in a wide variety of brain structures.
TL;DR: It is reported here that an inhibitor of guanylyl cyclase blocks the induction of LTP in the CA1 region of hippocampal slices, and activity-dependent long-lasting enhancement of the excitatory postsyn-aptic potential is produced.
Abstract: Several lines of evidence suggest that cyclic GMP might be involved in long-term potentiation (LTP) in the hippocampus. Arachidonic acid, nitric oxide and carbon monoxide, three molecules that have been proposed to act as retrograde messengers in LTP, all activate soluble guanylyl cyclase. We report here that an inhibitor of guanylyl cyclase blocks the induction of LTP in the CA1 region of hippocampal slices. Conversely, cGMP analogues produce long-lasting enhancement of the excitatory postsynaptic potential if they are applied at the same time as weak tetanic stimulation of the presynaptic fibres. The enhancement is spatially restricted, is not blocked by valeric acid (APV), nifedipine, or picrotoxin, and partially occludes LTP. This synaptic enhancement may be mediated by the cGMP-dependent protein kinase (PKG). Inhibitors of PKG block the induction of LTP, and activators of PKG produce activity-dependent long-lasting enhancement. These results suggest that guanylyl cyclase and PKG contribute to LTP, possibly as activity-dependent presynaptic effectors of retrograde messengers.
TL;DR: It is concluded that the mechanism of early LTP expression includes at least the presynaptic locus, and increases in the number of release sites and the probability of neurotransmitter release alone would not appear to account for the findings.
Abstract: Long-term potentiation (LTP) is a use-dependent form of synaptic plasticity that is of great interest as a potential cellular substrate underlying memory. It is important to determine the pre- and/or postsynaptic locus of LTP expression in order to study its underlying mechanisms. Despite intensive investigation, however, its locus of expression remains uncertain. It has been hypothesized that if LTP expression includes a presynaptic locus then it may alter the expression of another presynaptically mediated form of potentiation like paired-pulse facilitation (PPF), which is an increase in a second population excitatory postsynaptic potential when it is elicited shortly after a first. Previous authors have found no change in PPF in association with LTP. We re-examined the hypothesis, however, to reconcile the negative PPF data with other data that have suggested presynaptic involvement in LTP. Extracellular recordings were made in area CA1 of the rat hippocampal slice preparation. Surprisingly, PPF both increased and decreased significantly in association with LTP. The changes in PPF occurred in a predictable way, however. They correlated inversely with initial PPF magnitude so that a larger initial PPF was associated with a decrease in PPF with LTP while a smaller initial PPF was associated with an increase. Because PPF increased or decreased in individual slices in association with LTP, the average PPF of all slices did not change, in agreement with previous studies. The changes in PPF were also specific to LTP; that is, they were input specific, were not due to changes in inhibition or nonspecific effects of high-frequency stimulation, were not due to active postsynaptic currents or their nonlinear summation, and PPF changed with the same time course as LTP. We conclude that the mechanism of early LTP expression includes at least the presynaptic locus. Two hypotheses regarding the presynaptic mechanism underlying LTP expression, which are consistent with finding both increases and decreases in PPF with LTP, are (1) that there is an increase in the number of release sites with LTP or (2) that there is an increase in both the number of release sites and the probability of neurotransmitter release. Increases in the probability of neurotransmitter release alone would not appear to account for our findings since such increases have been associated only with decreases in PPF. Our findings do not exclude additional postsynaptic involvement.(ABSTRACT TRUNCATED AT 400 WORDS)
TL;DR: Immunocytochemical studies indicate that in the nNOS- mice as in wild-type mice, the endothelial form of NOS (eNOS) is expressed in CA1 neurons, suggesting that eNOS generates NO within the postsynaptic cell during LTP, suggesting the importance of NO in hippocampal synaptic plasticity.
Abstract: Long-term potentiation (LTP) is a persistent increase in synaptic strength implicated in certain forms of learning and memory In the CA1 region of the hippocampus, LTP is thought to involve the release of one or more retrograde messengers from the postsynaptic cell that act on the presynaptic terminal to enhance transmitter release One candidate retrograde messenger is the membrane-permeant gas nitric oxide (NO), which in the brain is released after activation of the neuronal-specific NO synthase isoform (nNOS) To assess the importance of NO in hippocampal synaptic plasticity, LTP was examined in mice where the gene encoding nNOS was disrupted by gene targeting In nNOS- mice, LTP induced by weak intensity tetanic stimulation was normal except for a slight reduction in comparison to that in wild-type mice and was blocked by NOS inhibitors, just as it was in wild-type mice Immunocytochemical studies indicate that in the nNOS- mice as in wild-type mice, the endothelial form of NOS (eNOS) is expressed in CA1 neurons These findings suggest that eNOS, rather than nNOS, generates NO within the postsynaptic cell during LTP
TL;DR: The role of mGluRs in the induction of LTP is fundamentally different from that of NMDA receptors and this work shows that the molecular switch is a new feature of LTB which has fundamental consequences for the understanding of synaptic plastic mechanisms.
Abstract: Pharmacological studies of long-term potentiation (LTP) in the hippocampus are starting to provide a molecular understanding of synaptic plastic processes which are believed to be important for learning and memory in vertebrates. In the CA1 region of the hippocampus, the synaptic activation of glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype is necessary for the induction of LTP under most experimental conditions. The synaptic activation of metabotropic glutamate receptors (mGluRs) is also needed for the induction of LTP. We now show that the role of mGluRs in the induction of LTP is fundamentally different from that of NMDA receptors. NMDA receptors initiate a molecular event that needs to be triggered each time a tetanus is delivered to induce LTP. In contrast, mGluRs activate a molecular switch which then negates the need for mGluR stimulation during the induction of LTP. This mGluR-activated switch is input-specific and can be turned off by a train of low-frequency stimulation. The molecular switch is a new feature of LTP which has fundamental consequences for our understanding of synaptic plastic mechanisms.
TL;DR: It is discovered in slices of rat visual cortex that reliable long-term potentiation (LTP) of synaptic responses in layer III could be elicited by theta burst stimulation delivered to a site in the middle of the cortical thickness, corresponding mainly to layer IV.
Abstract: We discovered in slices of rat visual cortex that reliable long-term potentiation (LTP) of synaptic responses in layer III could be elicited by theta burst stimulation delivered to a site in the middle of the cortical thickness, corresponding mainly to layer IV. This synaptic plasticity was reflected in the extracellular field potentials and intracellular EPSPs in layer III, but was not observed in the intracellular responses of layer V neurons, suggesting a preferential involvement of synapses on layer III neurons. Tetanus-induced LTP in this preparation was input specific, and was blocked by application of an NMDA receptor antagonist (but not by an antagonist of nitric oxide synthase). In addition, LTP of layer IV-evoked responses could also be produced reliably by pairing low-frequency synaptic stimulation (approximately 100 pulses at 1 Hz) with strong intracellular depolarization of layer III neurons. Thus, LTP in this circuit satisfies the definition of a "Hebbian" modification. Tetanic stimulation of the white matter, in sharp contrast, consistently failed to elicit LTP in layer III unless a GABAA receptor antagonist was applied to the slice. Analysis indicated that the critical difference between layer IV and white matter stimulation was not the magnitude of the responses to single stimuli delivered to the two sites, but that it might lie in the postsynaptic response during high-frequency stimulation. Consistent with this idea, "associative" LTP could be elicited from white matter when converging but independent inputs from the white matter and layer IV simultaneously received tetanic conditioning stimulation. A hypothetical model is presented to account for the differences between layer IV and white matter stimulation. According to this "plasticity gate hypothesis," inhibitory circuitry in layer IV normally acts as a sort of band-pass filter that constrains the types of activity patterns that can gain access to the modifiable synapses in layer III. By stimulating in layer IV, we have bypassed this filter and therefore do not need to block GABAA receptors to achieve the threshold for LTP in layer III.
TL;DR: A positive correlation between the magnitude of hippocampal LTP and a form of learning that depends on the hippocampus is revealed and a neural basis for sex differences in hippocampus-dependent learning tasks is suggested.
TL;DR: It is demonstrated that persistent changes in the functional interactions of cortical neurons can arise by activity-dependent mechanisms within the local horizontal connections and suggest a likely mechanism to recognize cortical representation patterns.
Abstract: 1. Field potential recordings were used in rat motor cortex (MI) slice preparations to investigate the potential for activity-dependent modifications in the effectiveness of synaptic connections fo...
TL;DR: It is found that LTP increases synaptic reliability, and LTD decreases it, both without a change in the size of those postsynaptic currents that do occur, thus LTD is a functional inverse of LTP.
Abstract: SYNAPTIC transmission in the hippocampus is rather unreliable, with many presynaptic action potentials failing to release neurotransmitter1–4. How is this unreliability affected by the alterations in synaptic strength seen in long-term potentiation (LTP)5 and long-term depression6,7 (LTD)? We find that LTP increases synaptic reliability, and LTD decreases it, both without a change in the size of those postsynaptic currents that do occur. Thus LTD is a functional inverse of LTP.
TL;DR: It is found that facilitation, augmentation and potentiation are caused by the continuing action of residual Ca2 + acting at a separate site fromfacilitation, and these sites are different from the molecular target triggering neurosecretion.
Abstract: At many synapses, the amount of transmitter released by action potentials increases progressively during a train of spikes. This enhancement of evoked transmitter release grows during tetanic stimulation with several time constants, each bearing a different name (facilitation: tens to hundreds of milliseconds; augmentation: several seconds; potentiation: several minutes), and the enhancement of release to test spikes after a tetanus decays with similar time constants. All these processes depend on presynaptic Ca2+ influx during the conditioning tetanus. It has often been proposed that these forms of synaptic plasticity are due to residual Ca2+ present in nerve terminals following conditioning activity. We tested this idea directly by using photolabile Ca2+ chelators to reduce residual Ca2+ following conditioning stimulation or to generate an artificial elevation in Ca2+ concentration, and observed the effects on synaptic transmission at crayfish neuromuscular junctions. We found that facilitation, augmentation and potentiation are caused by the continuing action of residual Ca2+. Augmentation and potentiation seem to arise from Ca2+ acting at a separate site from facilitation, and these sites are different from the molecular target triggering neurosecretion.
TL;DR: The data presented here indicate that long-term potentiation can be communicated between synapses on neighboring neurons by means of a diffusible messenger, which provides a mechanism for the cooperative strengthening of proximal synapses and may underlie a variety of plastic processes in the nervous system.
Abstract: The long-lasting increase in synaptic strength known as long-term potentiation has been advanced as a potential physiological mechanism for many forms of both developmental and adult neuronal plasticity. In many models of plasticity, intercellular communication has been proposed to account for observations in which simultaneously active neurons are strengthened together. The data presented here indicate that long-term potentiation can be communicated between synapses on neighboring neurons by means of a diffusible messenger. This distributed potentiation provides a mechanism for the cooperative strengthening of proximal synapses and may underlie a variety of plastic processes in the nervous system.
TL;DR: The data indicate that many neurons in each subfield of the hippocampus contain NMDAR-1 protein, although the intensity and distribution of immunoreactivity varied across regions, strata, and cellular compartments.
Abstract: The regional, cellular, and subcellular distributions of N-methyl-D-aspartate (NMDA) receptor subunit 1, NMDAR-1, were investigated in monkey hippocampus by using a monoclonal antibody directed against a fusion protein corresponding to aa 660-811 of NMDAR-1. The data indicate that many neurons in each subfield of the hippocampus contain NMDAR-1 protein, although the intensity and distribution of immunoreactivity varied across regions, strata, and cellular compartments. In stratum lucidum of CA3, mossy fiber axons were immunoreactive for NMDAR-1, which may correspond to previously hypothesized presynaptic receptors. NMDAR-1-labeled postsynaptic profiles were present in stratum radiatum of CA3 but were largely absent from stratum lucidum. Such intraneuronal segregation of glutamate receptor subunits or classes may be spatially correlated with afferent systems that exhibit laminar segregation and terminate in different portions of the postsynaptic dendritic tree. For example, in CA3 pyramidal cells, NMDA receptors are postsynaptic in distal apical dendrites (stratum radiatum) where NMDA-dependent long-term potentiation in rats is mediated by associational/commissural afferents, and are absent from proximal apical dendrites (stratum lucidum), where NMDA-independent long-term potentiation is mediated by the mossy fiber input.