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- Abbas, Abdul-Karim, 1959, et al.
(författare)
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Persistent LTP without triggered protein synthesis.
- 2009
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Ingår i: Neuroscience research. - : Elsevier BV. - 0168-0102. ; 63:1, s. 59-65
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Tidskriftsartikel (refereegranskat)abstract
- Protein synthesis is believed to be involved in stabilizing synaptic plasticity. Effects lasting longer than about 2-3h are considered to require synthesis of new proteins, implying a functional separation between early (E) and late (L) components. However, the issue of constitutive vs. new protein synthesis is still unclear, especially in young animals. Here, we examined the effects of two protein synthesis inhibitors, anisomycin and emetine, on long-term-potentiation (LTP) in CA1 area of hippocampal slices from 12- to 20-day-old rats. Either drug was applied from -30 min to +30 min with respect to LTP induction, a time window previously reported to be critical. However, the LTP remained stable under the entire recording period of 4h (anisomycin), or 8h (emetine). Proper preparation of emetine solution was evidenced by the fact that, in separate experiments, prolonged treatment with emetine gradually blocked baseline responses. Although no corresponding effect was observed with anisomycin, the drug was judged to be potent by its ability to inhibit yeast growth. The ability of anisomycin to inhibit protein synthesis was further confirmed by radiolabeling experiments assessing the degree of leucine incorporation. Our data suggest that LTP up to at least 8h is not dependent on triggered protein synthesis but can be attained by utilizing proteins already available at induction time.
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- Dozmorov, Mikhail, 1973, et al.
(författare)
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Contribution of AMPA and NMDA receptors to early and late phases of LTP in hippocampal slices.
- 2006
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Ingår i: Neuroscience research. - : Elsevier BV. - 0168-0102. ; 55:2, s. 182-8
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Tidskriftsartikel (refereegranskat)abstract
- Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor mediated responses were investigated in rat hippocampal slices under 4h of long-term potentiation (LTP) expression. A modified medium containing the NMDA receptor antagonist AP5 and low concentration of Mg(2+) was used to monitor isolated AMPA responses. NMDA components were determined from composite excitatory postsynaptic potentials (EPSPs) under brief (15-20 min) wash-out of AP5. LTP was induced in a medium with low concentration of AP5, resulting in an about two-fold larger increase of the AMPA component than of the NMDA component at both 1h and 4h after induction. Similar results were obtained if LTP was induced in "normal Mg(2+)" and the NMDA components were assessed at the end of experiment, from either composite or isolated NMDA EPSPs, with or without blockade of GABAergic inhibition. It is generally believed that LTP undergoes biochemical and/or structural conversions during the first few hours. Our study, however, shows constant expression of LTP, at least in terms of AMPA versus NMDA components, during this time. The data support the notion that LTP initiates as a predominant amplification of AMPA receptors and remains so for at least 4h.
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- Li, Rui, 1975
(författare)
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Chemical and stimulus-induced NMDA-dependent plasticity and the possible involved mechanisms
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Long-term potentiation (LTP) and long-term depression (LTD) are considered as the most important forms of synaptic plasticity involved in learning and memory. The traditional way to induce LTP and LTD is by electric stimulation leading to activation of NMDA-R. Later research also revealed a form of NMDA-dependent plasticity induced by direct application of NMDA. I have investigated the involvement of AMPA-R and NMDA-R in NMDA-induced LTD as well as their contribution to early and late phases of stimulus-induced LTP; examined the roles of different NMDA-R subunits in several forms of synaptic plasticity; and tried to elucidate the possible mechanisms underlying NMDA-induced plasticity. The experiments were performed in hippocampal slices, 400 ?m thick, from 12 to 20 days old Sprague-Dawley rats. Extracellular recording was used to study field excitatory postsynaptic potential (EPSPs) in the CA1 apical dendritic layer. Isolated AMPA EPSPs were obtained in standard solution or in low Mg2+ containing NMDA-R blocker AP5. Composite EPSPs were recorded in low Mg2+ whereas isolated NMDA EPSPs were expressed in low Mg2+ solution with AMPA-R blocker CNQX. LTP was elicited by HFS trains (100 impulses, 100 Hz) or in some cases theta-burst stimulation (10 times 4 impulses, 100 Hz, 200 ms interval). NMDA-induced LTD was achieved by brief (4 min) bath application of NMDA. The results showed that 20-50 ?M NMDA application persistently depressed both AMPA and NMDA responses to a nearly equal extent. In addition, a waveform prolongation of AMPA but not of NMDA EPSPs occurred 15-25 min after NMDA application. On the contrary, stimulus-induced LTP potentiated AMPA and NMDA responses to a different degree, with about two-fold larger increase of AMPA than NMDA component at both 1h and 4 h after induction. Different tests revealed noninvolvement of voltage dependent channels as well as GABAa-ergic inhibition in the NMDA-induced prolongation of AMPA EPSPs. However, EPSP prolongation was occluded by a similar change induced by AMPA-R modulator cyclothiazide (CTZ); and facilitated by AMPA-R modulator aniracetam. The comparison of NMDA-induced effects in pathways with and without prior LTP demonstrated a larger depression and smaller waveform change in the LTP pathway. LTP and NMDA-induced LTD, as well as a form of stimulus-induced LTD, were all largely prevented by NVP-AAM077, a blocker of NMDA receptors that contain subunits of type NR2A. However, the blockade in these cases could be counteracted by general amplification of NMDA responses by lowering the perfused Mg2+ concentration. Blockers of NR2B- containing NMDA receptors by Ro25-6981 or Ifenprodil had no effect on the two forms of LTD whereas LTP was partially blocked. It was found that subunits NR2A and NR2B contributed to about 80% and 20%, respectively, of isolated NMDA EPSPs. Our results demonstrate that NMDA applied on brain tissue induces multiple synaptic plasticity. Modifications underlying NMDA-induced LTD differ from those in LTP in several respects; however, these two forms of plasticity also interact, suggesting a possible relation. This is also supported by the fact that both LTP and NMDA-induced LTD require activation of NR2A containing NMDA receptors, and that both LTP and NMDA-induced waveform changes interact with AMPA receptor modulators. Notably, NR2A subunits play an essential role in all types of synaptic plasticity examined in this study whereas NR2B also contribute under certain circumstances. We therefore believe that the final magnitude and temporal pattern of Ca2+ influx in the spine is a key factor determining the induced synaptic plasticity.
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