In this chapter, we transitioned from thinking about LTP as a straightforward activity-dependent form of synaptic plasticity. We saw, for example, that LTP induction is subject to a great number of modulatory influences. Also, temporal integration mechanisms are key to regulating LTP induction. In addition to these issues, we discussed the fact that regulating membrane excitability, directly by modulating membrane ion channels and indirectly through local GABAergic circuits, can play a pronounced role in regulating LTP induction. Finally, we noted the existence of altered probability of action potential firing as a persisting effect superimposed upon synaptic potentiation. All these issues are key to thinking about the roles for LTP in memory formation in the behaving animal. The synapse integrates a wide variety of signals in order to make a biochemical decision whether to trigger lasting change. In the next three chapters we will take our analysis to the next level of detail and discuss the molecular mechanisms that allow for this complex physiologic information processing to occur.
1. Dawkins, R. (1986). The blind watchmaker, 1st American edn. New York: Norton.
2. Choi, S., Klingauf, J., and Tsien, R. W. (2000). "Postfusional regulation of cleft glutamate concentration during LTP at 'silent synapses'." Nat. Neurosci. 3:330-336.
3. Bolshakov, V. Y., Golan, H., Kandel, E. R., and Siegelbaum, S. A. (1997). "Recruitment of new sites of synaptic transmission during the cAMP-dependent late phase of LTP at CA3-CA1 synapses in the hippocampus." Neuron 19:635-651.
4. Nicoll, R. A., and Malenka, R. C. (1999). "Expression mechanisms underlying NMDA receptor-dependent long-term potentiation." Ann. NY Acad. Sci. 868:515-525.
6. Bekkers, J. M., and Stevens, C. F. (1990). "Presynaptic mechanism for long-term potentia-tion in the hippocampus." Nature 346:724-729.
7. Malinow, R. (1991). "Transmission between pairs of hippocampal slice neurons: quantal levels, oscillations, and LTP." Science 252:722-724.
8. Dolphin, A. C., Errington, M. L., and Bliss, T. V. (1982). "Long-term potentiation of the perforant path in vivo is associated with increased glutamate release." Nature 297:496-498.
9. Zakharenko, S. S., Zablow, L., and Siegelbaum, S. A. (2001). "Visualization of changes in presynaptic function during long-term synaptic plasticity." Nat. Neurosci. 4:711-717.
10. Malgaroli, A., Ting, A. E., Wendland, B., Bergamaschi, A., Villa, A., Tsien, R. W., and Scheller, R. H. (1995). "Presynaptic component of long-term potentiation visualized at individual hippocampal synapses." Science 268:1624-1628.
11. Bliss, T. V., and Lomo, T. (1973). "Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path." J. Physiol. 232:331-356.
12. Johnston, D., and Amaral, D. G. (1998). "Hippocampus." In: The synaptic organization of the brain edited by Shepherd GM, 4th ed. New York: Oxford University Press; 417-458.
13. McMahon, L. L., and Kauer, J. A. (1997). "Hip-pocampal interneurons express a novel form of synaptic plasticity." Neuron 18:295-305.
14. Lu, Y. M., Mansuy, I. M., Kandel, E. R., and Roder, J. (2000). "Calcineurin-mediated LTD of GABAergic inhibition underlies the increased excitability of CA1 neurons associated with LTP." Neuron 26:197-205.
15. Johnston, D., Hoffman, D. A., Colbert, C. M., and Magee, J. C. (1999). "Regulation of back-propagating action potentials in hippocampal neurons." Curr. Opin. Neurobiol.9:288-292.
16. Scharfman, H. E., and Sarvey, J. M. (1985). "Postsynaptic firing during repetitive stimulation is required for long-term potentiation in hippocampus." Brain Res. 331:267-274.
17. Linden, D. J. (1999). "The return of the spike: post-synaptic action potentials and the induction of LTP and LTD." Neuron 22:661-666.
18. Mott, D. D., and Lewis, D. V. (1991). "Facilitation of the induction of long-term potentiation by GABAB receptors." Science 252:1718-1720.
19. Chapman, C. A., Perez, Y., and Lacaille, J. C. (1998). "Effects of GABA(A) inhibition on the expression of long-term potentiation in CA1 pyramidal cells are dependent on tetanization parameters." Hippocampus 8:289-298.
20. Davies, C. H., Starkey, S. J., Pozza, M. F., and Collingridge, G. L. (1991). "GABA autoreceptors regulate the induction of LTP." Nature 349:609-611.
21. Roberson, E. D., English, J. D., and Sweatt, J. D. (1996). "A biochemist's view of long-term potentiation." Learn. Mem. 3:1-24.
22. Winder, D. G., Mansuy, I. M., Osman, M., Moallem, T. M., and Kandel, E. R. (1998). "Genetic and pharmacological evidence for a novel, intermediate phase of long-term potentiation suppressed by calcineurin." Cell. 92:25-37.
23. Shulz, P: Personal communication.
24. Malinow, R., Madison, D. V., and Tsien, R. W. (1988). "Persistent protein kinase activity underlying long-term potentiation." Nature 335:820-824.
25. Kamondi, A., Acsady, L., and Buzsaki, G. (1998). "Dendritic spikes are enhanced by cooperative network activity in the intact hippocampus." J. Neurosci. 18:3919-3928.
26. Malinow, R., Schulman, H., and Tsien, R. W. (1989) "Inhibition of postsynaptic PKC or CaMKII blocks induction but not expression of LTP." Science 245:862-866.
27. Malenka, R. C., Kauer, J. A., Perkel, D. J., Mauk, M. D., Kelly, P. T., Nicoll, R. A., and Waxham, M. N. (1989). "An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation." Nature 340:554-557.
28. Levenson, J., Weeber, E., Selcher, J. C., Kategaya, L. S., Sweatt, J. D., and Eskin A. (2002). "Long-term potentiation and contextual fear conditioning increase neuronal glutamate uptake." Nat. Neurosci. 5:155-161.
29. Renger, J. J., Egles, C., and Liu, G. (2001). "A developmental switch in neurotransmitter flux enhances synaptic efficacy by affecting AMPA receptor activation." Neuron 29:469-484.
30. Lee, H. K., Kameyama, K., Huganir, R. L., and Bear, M. F. (1998). "NMDA induces long-term synaptic depression and dephosphorylation of the GluR1 subunit of AMPA receptors in hippocampus." Neuron 21:1151-1162.
31. Lee, H. K., Barbarosie, M., Kameyama, K., Bear, M. F., and Huganir, R. L. (2000). "Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity." Nature 405:955-959.
32. Kemp, N., McQueen, J., Faulkes, S., and Bashir, Z. I. (2000). "Different forms of LTD in the CA1 region of the hippocampus: role of age and stimulus protocol." Eur. J. Neurosci. 12:360-366.
33. Thomas, M. J., Moody, T. D., Makhinson, M., and O'Dell, T. J. (1996). "Activity-dependent beta-adrenergic modulation of low frequency stimulation induced LTP in the hippocampal CA1 region." Neuron 17:475-482.
34. Lu, B., and Chow, A. (1999). "Neurotrophins and hippocampal synaptic transmission and plasticity." J. Neurosci. Res. 58:76-87.
35. Gottschalk, W., Pozzo-Miller, L. D., Figurov, A., and Lu, B. (1998). "Presynaptic modulation of synaptic transmission and plasticity by brain-derived neurotrophic factor in the developing hippocampus." J. Neurosci. 18:6830-6839.
36. Xu, B., Gottschalk, W., Chow, A., Wilson, R. I., Schnell, E., Zang, K., Wang, D., Nicoll, R. A., Lu, B., and Reichardt, L. F. (2000). "The role of brain-derived neurotrophic factor receptors in the mature hippocampus: modulation of long-term potentiation through a presynaptic mechanism involving TrkB." J. Neurosci. 20:6888-6897.
37. Schafe, G. E., Atkins, C. M., Swank, M. W., Bauer, E. P., Sweatt, J. D., and LeDoux, J. E. (2000). "Activation of ERK/MAP kinase in the amygdala is required for memory consolidation of pavlovian fear conditioning." J. Neurosci. 20:8177-8187.
LTP Induction Biochemistry J. David Sweatt, Acrylic on canvas, 2002
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