38,956 research outputs found

    Long-Term Potentiation: One Kind or Many?

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    Do neurobiologists aim to discover natural kinds? I address this question in this chapter via a critical analysis of classification practices operative across the 43-year history of research on long-term potentiation (LTP). I argue that this 43-year history supports the idea that the structure of scientific practice surrounding LTP research has remained an obstacle to the discovery of natural kinds

    Synaptic tagging and capture in the living rat

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    In isolated hippocampal slices, decaying long-term potentiation can be stabilized and converted to late long-term potentiation lasting many hours, by prior or subsequent strong high-frequency tetanization of an independent input to a common population of neurons—a phenomenon known as ‘synaptic tagging and capture’. Here we show that the same phenomenon occurs in the intact rat. Late long-term potentiation can be induced in CA1 during the inhibition of protein synthesis if an independent input is strongly tetanized beforehand. Conversely, declining early long-term potentiation induced by weak tetanization can be converted into lasting late long-term potentiation by subsequent strong tetanization of a separate input. These findings indicate that synaptic tagging and capture is not limited to in vitro preparations; the past and future activity of neurons has a critical role in determining the persistence of synaptic changes in the living animal, thus providing a bridge between cellular studies of protein synthesis-dependent synaptic potentiation and behavioural studies of memory persistence

    Long-Term Potentiation and Memory

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    One of the most significant challenges in neuroscience is to identify the cellular and molecular processes that underlie learning and memory formation. The past decade has seen remarkable progress in understanding changes that accompany certain forms of acquisition and recall, particularly those forms which require activation of afferent pathways in the hippocampus. This progress can be attributed to a number of factors including well-characterized animal models, well-defined probes for analysis of cell signaling events and changes in gene transcription, and technology which has allowed gene knockout and overexpression in cells and animals. Of the several animal models used in identifying the changes which accompany plasticity in synaptic connections, long-term potentiation (LTP) has received most attention, and although it is not yet clear whether the changes that underlie maintenance of LTP also underlie memory consolidation, significant advances have been made in understanding cell signaling events that contribute to this form of synaptic plasticity. In this review, emphasis is focused on analysis of changes that occur after learning, especially spatial learning, and LTP and the value of assessing these changes in parallel is discussed. The effect of different stressors on spatial learning/memory and LTP is emphasized, and the review concludes with a brief analysis of the contribution of studies, in which transgenic animals were used, to the literature on memory/learning and LTP

    Melatonin and Its Effect on Learning and Memory

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    Melatonin is a neurohormone produced by the pineal gland and secreted into the body in a circadian rhythm. Melatonin is known to be involved in many vital body functions, including sleep, reproduction, and immune response. Exogenous melatonin, sold as over the counter natural supplements in drugstores, is commonly taken by many people to help cure various ailments. Melatonin also plays a role in the hippocampus. This paper investigates the effects of melatonin on long-term potentiation in the hippocampus. Long-term potentiation, described as a long-lasting strengthening of synapses between nerve cells, is thought to be responsible for long-term memory retention. It is found that melatonin has a negative effect on long-term potentiation, inhibiting its magnitude. As long-term potentiation is related to some forms of learning and memory, melatonin inhibits learning and memory too. The practice of taking melatonin supplements causes one’s long-term potentiation to be inhibited to a greater degree than it would be under normal conditions and can significantly impact one’s learning and memory. In conclusion, although more studies need to be conducted, one should be wary and display caution before using melatonin supplements with any regularity

    Tonic and phasic nitric oxide signals in hippocampal long-term potentiation

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    Nitric oxide ( NO) participates in long-term potentiation (LTP) and other forms of synaptic plasticity in many different brain areas but where it comes from and how it acts remain controversial. Using rat and mouse hippocampal slices, we tested the hypothesis that tonic and phasic NO signals are needed and that they derive from different NO synthase isoforms. NMDA increased NO production in a manner that was potently inhibited by three different neuronal NO synthase ( nNOS) inhibitors. Tonic NO could be monitored after sensitizing guanylyl cyclase-coupled NO receptors, allowing the very low ambient NO concentrations to be detected by cGMP measurement. The levels were unaffected by inhibition of NMDA receptors, nNOS, or the inducible NO synthase ( iNOS). iNOS was also undetectable in protein or activity assays. Tonic NO was susceptible to agents inhibiting endothelial NO synthase ( eNOS) and was missing in eNOS knock-out mice. The eNOS knock-out sexhibited a deficiency in LTP resembling that seen in wild-types treated with a NO synthase inhibitor. LTP in the knock-outs could be fully restored by supplying a low level of NO exogenously. Inhibition of nNOS also caused a major loss of LTP, particularly of late-LTP. Again, exogenous NO could compensate, but higher concentrations were needed compared with those restoring LTP in the eNOS knock-outs. It is concluded that tonic and phasic NO signals are both required for hippocampal LTP and the two are generated, respectively, by eNOS and nNOS, the former in blood vessels and the latter in neurons

    Ovarian Hormones, Aging and Stress on Hippocampal Synaptic Plasticity

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    The ovarian steroid hormones estradiol and progesterone regulate a wide variety of non-reproductive functions in the central nervous system by interacting with molecular and cellular processes. A growing literature from studies using rodent models suggests that 17β-estradiol, the most potent of the biologically relevant estrogens, enhances synaptic transmission and the magnitude of long-term potentiation recorded from in vitro hippocampal slices. In contrast, progesterone has been shown to decrease synaptic transmission and reduce hippocampal long-term potentiation in this model system. Hippocampal long-term depression, another form of synaptic plasticity, occurs more prominently in slices from aged rats. A decrease in long-term potentiation magnitude has been recorded in hippocampal slices from both adult and aged rats behaviorally stressed just prior to hippocampal slice tissue preparation and electrophysiological recording. 17β-estradiol modifies synaptic plasticity in both adult and aged rats, whether behaviorally stressed or not by enhancing long-term potentiation and attenuating long-term depression. The studies discussed in this review provide an understanding of new approaches used to investigate the protective effects of ovarian hormones against aging and stress, and how these hormones impact age and stress-related learning and memory dysfunction

    Long-Term Potentiation in Isolated Dendritic Spines

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    BACKGROUND:In brain, N-methyl-D-aspartate (NMDA) receptor (NMDAR) activation can induce long-lasting changes in synaptic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor (AMPAR) levels. These changes are believed to underlie the expression of several forms of synaptic plasticity, including long-term potentiation (LTP). Such plasticity is generally believed to reflect the regulated trafficking of AMPARs within dendritic spines. However, recent work suggests that the movement of molecules and organelles between the spine and the adjacent dendritic shaft can critically influence synaptic plasticity. To determine whether such movement is strictly required for plasticity, we have developed a novel system to examine AMPAR trafficking in brain synaptosomes, consisting of isolated and apposed pre- and postsynaptic elements. METHODOLOGY/PRINCIPAL FINDINGS:We report here that synaptosomes can undergo LTP-like plasticity in response to stimuli that mimic synaptic NMDAR activation. Indeed, KCl-evoked release of endogenous glutamate from presynaptic terminals, in the presence of the NMDAR co-agonist glycine, leads to a long-lasting increase in surface AMPAR levels, as measured by [(3)H]-AMPA binding; the increase is prevented by an NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP5). Importantly, we observe an increase in the levels of GluR1 and GluR2 AMPAR subunits in the postsynaptic density (PSD) fraction, without changes in total AMPAR levels, consistent with the trafficking of AMPARs from internal synaptosomal compartments into synaptic sites. This plasticity is reversible, as the application of AMPA after LTP depotentiates synaptosomes. Moreover, depotentiation requires proteasome-dependent protein degradation. CONCLUSIONS/SIGNIFICANCE:Together, the results indicate that the minimal machinery required for LTP is present and functions locally within isolated dendritic spines

    State based model of long-term potentiation and synaptic tagging and capture

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    Recent data indicate that plasticity protocols have not only synapse-specific but also more widespread effects. In particular, in synaptic tagging and capture (STC), tagged synapses can capture plasticity-related proteins, synthesized in response to strong stimulation of other synapses. This leads to long-lasting modification of only weakly stimulated synapses. Here we present a biophysical model of synaptic plasticity in the hippocampus that incorporates several key results from experiments on STC. The model specifies a set of physical states in which a synapse can exist, together with transition rates that are affected by high- and low-frequency stimulation protocols. In contrast to most standard plasticity models, the model exhibits both early- and late-phase LTP/D, de-potentiation, and STC. As such, it provides a useful starting point for further theoretical work on the role of STC in learning and memory
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