Abstract
It is thought that activity-dependent changes in synaptic efficacy driven by biochemical pathways responsive to the action of the excitatory neuro-transmitter glutamate are critical components of the mechanisms responsible for memory formation. In particular, the early activation of the NMDA (rNMDA) and AMPA (rAMPA) subtypes of ionotropic glutamate receptors has been demonstrated to be a necessary event for the acquisition of several types of memory. In the rat, consolidation of the long-term memory for a one-trial, step-down inhibitory avoidance task is blocked by antagonists of the rNMDA and rAMPA infused into the CA1 region of the dorsal hippocampus early after training and is associated with a rapid and reversible increase in the total number of [3H]AMPA binding sites. The learning-induced increase in [3H]AMPA is accompanied by translocation of the GluR1 subunit of the rAMPA to the post-synaptic terminal together with its phosphorylation at Ser831. In addition, learning of the mentioned fear-motivated task induces the activation and rNMDA-dependent translocation of CaMKII to the post-synaptic density. Inhibition of this protein kinase as well as blockade of the rNMDA abolishes both learning-induced translocation of GluR1 and its phosphorylation.
Our data suggest that learning of an avoidance task enhances hippocampal rAMPA signaling through rNMDA and CaMKII-dependent mechanisms.
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References
Barria A, D Muller, V Derkach, L Griffith and T Soderling (1997) Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation.Science 276, 2042–2045.
Bayer K, P De Koninck, A Leonard, J Hell and H Schulman (2001) Interaction with the NMDA receptor locks CaMKII in an active conformation.Nature 411, 801–805.
Bevilaqua L, P Ardenghi, N Schroder, E Bromberg, PK Schmitz, E Schaeffer, J Quevedo, M Bianchin, R Walz, JH Medina and I Izquierdo (1997) Drugs acting upon the cyclic adenosine monophosphate/protein kinase A signalling pathway modulate memory consolidation when given late after training into rat hippocampus but not amygdala.Behav. Pharmacol. 8, 331–338.
Bevilaqua LR, M Cammarota, G Paratcha, ML de Stein, I Izquierdo and JH Medina (1999) Experience-dependent increase in cAMP-responsive element binding protein in synaptic and nonsynaptic mitochondria of the rat hippocampus.Eur. J. Neurosci. 11, 3753–3756.
Braun A and H Schulman (1995) The multifunctional Ca2+/calmod-ulin-dependent protein kinase, from form to function.Annu. Rev. Physiol. 57, 417–4452.
Brun V, K Ytterbo, R Morris, M Moser and E Moser (2001) Retrograde amnesia for spatial memory induced by NMDA receptor-mediated long-term potentiation.J. Neurosci. 21, 356–362.
Cammarota M, I Izquierdo, C Wolfman, M Levi de Stein, R Bernabeu, D Jerusalinsky and JH Medina (1995) Inhibitory avoidance training induces rapid and selective changes in [3H]AMPA receptor binding in the rat hippocampal formation.Neurobiol. Learn. Mem. 64, 257–264.
Cammarota M, G Paratcha, M Levi de Stein, R Bernabeu, I Izquierdo and JH Medina (1997). B-50/GAP-43 phosphorylation and PKC activity are increased in rat hippocampal synaptosomal membranes after an inhibitory avoidance training.Neurochem. Res. 22, 499–505.
Cammarota M, R Bernabeu, M Levi De Stein, I Izquierdo and JH Medina (1998) Learning-specific, time-dependent increases in hippocampal Ca2+/calmodulin-dependent protein kinase II activity and AMPA GluR1 subunit immunoreactivity.Eur. J. Neurosci. 10, 2669–2676.
Cammarota M, G Paratcha, LR Bevilaqua, M Levi de Stein, M Lopez, A Pellegrino de Iraldi, I Izquierdo and JH Medina (1999) Cyclic AMP-responsive element binding protein in brain mitochondria.J. Neurochem.72, 2272–2277.
Cammarota M, LR Bevilaqua, P Ardenghi, G Paratcha, M Levi de Stein, I Izquierdo and JH Medina (2000a) Learning-associated activation of nuclear MAPK, CREB and Elk-1, along with Fos production, in the rat hippocampus after a one-trial avoidance learning, abolition by NMDA receptor blockade.Brain Res. Mol. Brain Res. 76, 36–46.
Cammarota M, ML de Stein, G Paratcha, LR Bevilaqua, I Izquierdo and JH Medina (2000b) Rapid and transient learning-associated increase in NMDA NR1 subunit in the rat hippocampus.Neurochem. Res. 25, 567–572.
De Koninck P and H Schulman (1998) Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations.Science 279, 227–230.
Fukunaga K, L Stoppini, E Miyamoto and D Muller (1993) Long term potentiation is associated with an increased activity of Ca2+/calmodulin-dependent protein kinase II.J. Biol. Chem. 268, 7863–7867.
Fukunaga K, D Muller and E Miyamoto (1995) Increased phosphorylation of Ca2+/calmodulin-dependent protein kinase II and its endogenous substrates in the induction of long-term potentia-tion.J. Biol. Chem. 270, 6119–6124.
Fukunaga K, D Muller D and E Miyamoto (1996) CaM kinase II in long-term potentiation.Neurochem. Int. 28, 343–358.
Hanson P and H Schulman (1992) Neuronal Ca2+/calmodulin-dependent protein kinases.Annu. Rev. Biochem. 61, 559–601.
Hanson P, T Meyer, L Stryer and H Schulman (1994) Dual role of calmodulin in autophosphorylation of multifunctional CaM kinase may underlie decoding of calcium signals.Neuron 12, 943–956.
Hayashi Y, S Shi, J Esteban, A Piccini, J Poncer and R Malinow (2000) Driving AMPA receptors into synapses by LTP and CaMKII, requirement for GluR1 and PDZ domain interaction.Science 287, 2262–2267.
Hinds H, S Tonegawa and R Malinow (1998) CA1 long-term potentiation is diminished but present in hippocampal slices from aCaMKII mutant mice.Learn. Mem. 5, 344–354.
Holscher C (1999) Synaptic plasticity and learning and memory, LTP and beyond.J. Neurosci. Res. 58, 62–75.
Isaac JT, RA Nicoll and RC Malenka (1995) Evidence for silent synapses, implications for the expression of LTP.Neuron 15, 427–434.
Isaac JT, SH Oliet, GO Hjelmstad, RA Nicoll and RC Malenka (1996) Expression mechanisms of long-term potentiation in the hippocampus.Physiol. (Paris) 90, 299–303.
Liao D, R Scannevin and R Huganir (2001) Activation of silent synapses by rapid activity-dependent synaptic recruitment of AMPA receptors.J. Neurosci. 21, 6008–6017.
Lin B, FA Brucher, LL Colgin and G Lynch (2002) Long-term potentiation alters the modulator pharmacology of AMPA-type glutamate receptors.J. Neurophysiol. 87, 2790–2800.
Lisman J, H Schulman and H Cline (2002) The molecular basis of CaMKII function in synaptic and behavioural memory.Nat. Rev. Neurosci. 3, 175–190.
Lledo P, G Hjelmstad, S Mukherfi, T Soderling, R Malenka and R Nicoll (1995) Ca2+/calmodulin-dependent protein kinase II and long-term potentiation enhance synaptic transmission by the same mechanism.Proc. Natl. Acad. Sci. USA 92, 11175–11179.
Malenka RC and RA Nicoll (1993) NMDA-receptor-dependent synaptic plasticity, multiple forms and mechanisms.Trends Neurosci. 16, 521–527.
Mammen A, K Kameyama, K Roche and R Huganir (1997) Phosphorylation of the ?-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit by calcium/calmodulin-dependent kinase II.J. Biol. Chem. 272, 32528–32533.
Martin S, P Grimwood and R Morris (2000) Synaptic plasticity and memory, an evaluation of the hypothesis.Annu. Rev. Neurosci. 23, 649–711.
Nicoll RA and RC Malenka (1999) Expression mechanisms underlying NMDA receptor-dependent long-term potentiation.Ann. NY Acad. Sci. 868, 515–525.
Otmakhov N, L Griffith and J Lisman (1997) Postsynaptic inhibitors of Ca2+/calmodulin-dependent protein kinase type II block induction but not maintenance of pairing induced long-term potentiation.J. Neurosci. 17, 5357–5365.
Ouyang Y, A Rosenstein, G Kreiman, E Schuman and M Kennedy (1999) Tetanic stimulation leads to increased accumulation of Ca2+/calmodulin-dependent protein kinase II via dendritic protein synthesis in hippocampal neurons.J. Neurosci. 19, 7823–7833.
Paratcha G, M Furman, L Bevilaqua, M Cammarota, M Vianna, ML de Stein, I Izquierdo and JH Medina (2000) Involvement of hippocampal PKCbetaI isoform in the early phase of memory formation of an inhibitory avoidance learning.Brain Res. 855, 199–205.
Paxinos G and C Watson (1986)The Rat in Stereotaxic Coordinates (Academic Press, San Diego, USA).
Sacchetti B, C Lorenzini, E Baldi, C Bucherelli, M Roberto, G Tassoni and M Brunelli (2001) Long-lasting hippocampal poten-tiation and contextual memory consolidation.Eur. J. Neurosci. 13, 2291–2298.
Shi S, Y Hayashi, R Petralia, S Zaman, R Wenthold, K Svoboda and R Malinow (1999) Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation.Science 284, 1811–1816.
Soderling TR and VA Derkach (2000) Postsynaptic protein phosphorylation and LTP.Trends Neurosci. 23, 75–80.
Strack S and R Colbran (1998) Autophosphorylation-dependent targeting of calcium/calmodulin-dependent protein kinase II by the NR2B subunit of theN-methyl-D-aspartate receptor.J. Biol. Chem. 273, 20689–20692.
Tan S, R Wenthold and T Soderling (1994) Phosphorylation of AMPA-type glutamate receptors by calcium/calmodulin-depend-ent protein kinase II and protein kinase C in cultured hippocam-pal neurons.J. Neurosci. 14, 1123–1129.
Wang J and P Kelly (1995) Postsynaptic injection of Ca2+/calmod-ulin induces synaptic potentiation requiring CaMKII and PKC activity.Neuron 15, 443–452.
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Cammarota, M., Bevilaqua, L.R.M., Bonini, J.S. et al. Hippocampal glutamate receptors in fear memory consolidation. neurotox res 6, 205–211 (2004). https://doi.org/10.1007/BF03033222
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DOI: https://doi.org/10.1007/BF03033222