Point number 6 begins a transition. Thus far, we have been discussing the mechanisms for regulating postsynaptic calcium and its immediate effectors, mechanism that determine if an LTP-inducing level of calcium is reached. Point 6 transitions us into the mechanisms whereby this triggering level of calcium is converted into a persisting signal that maintains LTP. As described in the beginning of the chapter, the details of these mechanisms are dealt with in Chapter 7 (for E-LTP) and Chapter 8 (for L-LTP). In addition in those chapters, we will discuss the targets of the persisting signals that result in the expression of LTP physiologically.
VIII. SUMMARY—MODELS FOR BIOCHEMICAL INFORMATION PROCESSING IN LTP INDUCTION
In this chapter, we have discussed five categories of molecular components and processes that are involved in LTP induction. It is very important not to think of
these in isolation from each other—they are functional categories to help organize the complex biochemical machinery of LTP induction, not compartmentalized biochemical processes in the cell! It is a useful intellectual exercise to think up ways to mix and match the categories and allow them to interact. The interactions of these various processes are what allow the synapse to serve in its role as a molecular decision maker.
We need to begin to think of the synapse as an immensely complicated information processing machine. It integrates a plethora of biochemical signals and computes, based on a number of molecular inputs, whether to trigger a lasting molecular change. This model of synaptic function allows for the necessary sophistication required for triggering memory formation in the animal in vivo. By way of providing a summary and overview for this chapter, I will finish up with a specific example of how these processes might interact. Please keep in mind that this example is illustrative and somewhat speculative.
This example is a combination of the NMDA receptor in its classical role, the cAMP gate, PKC activation of ERK, and potassium channel regulation by ERK. CaMKII activation is taken for our purposes as necessary for LTP induction, as we will discuss in the next chapter. The model is actually not even a far-fetched idea; it draws directly from data published by Manny Landau and colleagues (1, 79), Danny Winder and his collaborators (3), Tom O'Dell's group (2), and several of my colleagues (32-35). The model is schematized in Figure 8.
Imagine that LTP is going to be triggered by a back-propagating action potential (bpAP), caused in response to strong firing at a distal synapse, coupled with local synaptic glutamate. As we have discussed, this is because NMDA receptor activation is going to require bpAP-associated membrane depolarization coupled with synaptic glutamate at the synapse of interest. In addition, imagine that Kv4.2 channels would limit the capacity of the bpAP to reach the synapse and thus depolarize the NMD A receptor, except that a PLC/ PKC-coupled muscarinic ACh receptor has activated ERK and down-regulated these channels. Thus, the muscarinic receptor has gated the bpAP and allowed it to enter the relevant dendritic region. Let's say there's modest NMDA receptor activation and the calcium influx through the NMDA receptor would be insufficient to cause robust CaMKII activation (and hence LTP), except that the cAMP gate has been opened in the vicinity due to local beta-adrenergic receptor activation by NE. This amplification allows robust CaMKII activation and LTP induction.
In this example, a strong synaptic input, plus a weak synaptic input and two neuro-modulatory inputs, has uniquely triggered lasting synaptic plasticity: four-way coincidence detection. It is a molecular analogue of a common behavioral situation: an aroused animal (NE) receiving a salient environmental cue (strong synaptic input) at the peak of the theta rhythm (ACh) coupled with a second sensory signal (weak synaptic input). The resulting increase in synaptic strength might contribute to the animal forming an associative memory for the event.
It's also completely straightforward to construct a five-way coincidence detection system. All that you have to do is add one more of the components described in this chapter—synergistic activation of ERK by two receptors, BDNF modulation of presynaptic glutamate release, or Ephrin modulation of NMDA receptor function via src. With longer-lasting extracellular signals like the Ephrins or reelin or BDNF, it is easy to construct a temporal component to the model so that the synapse can determine its set-point for LTP based on its recent history, or the recent history of other nearby neurons.
The point of these examples is to illustrate how the molecular complexity of LTP induction can require that a precise and multifactorial set of conditions be met in order to trigger plasticity. This allows for sophisticated information processing at the synaptic level. It allows for complex decision making at the molecular and cellular level. The complex biochemical machinery of the synapse allows for a complicated logic to operate in determining whether a persisting effect is triggered in the CNS. Moreover, while we have focused on hippocampal LTP specifically, these issues and mechanisms are almost certainly involved in hippocampus-dependent learning in the intact animal and at a variety of sites outside the hippocampus, for example the cortex and amygdala. We will return to this issue in Chapter 9.
As a final parting comment, I will note that in my estimation the Hebb model concerning activity-dependent synap-tic plasticity in the CNS is inadequate. Strengthening of synaptic connections simply based upon repetitive firing is insufficient to account for memory formation in my opinion. This line of thought comes out of considering all the many processes we have discussed in this chapter. The molecular complexity of LTP induction has implications for thinking about memory formation in general terms. The synapse is a complex signal integration machine. To integrate information and decide whether to change its state, it responds to multiple signals, and its recent history. It's not just static and it's not just Hebbian. I posit that, in the functioning hippocampus, one presynaptic terminal merely consistently or repeatedly participating in the firing of a postsynaptic neuron typically is not enough to trigger plasticity—many more factors come into play, factors that are critical in allowing the synapse sufficient computational power to perform sophisticated information processing.
1. Brown, G. P., Blitzer, R. D., Connor, J. H., Wong, T., Shenolikar, S., Iyengar, R., and Landau, E. M.
(2000). "Long-term potentiation induced by theta frequency stimulation is regulated by a protein phosphatase-1-operated gate." J. Neurosci. 20:7880-7887.
2. Watabe, A. M., Zaki, P. A., and O'Dell, T. J. (2000). "Coactivation of beta-adrenergic and cholinergic receptors enhances the induction of long-term potentiation and synergistically activates mitogen-activated protein kinase in the hippocam-pal CA1 region." J. Neurosci. 20:5924-5931.
3. Winder, D. G., Martin, K. C., Muzzio, I. A., Rohrer, D., Chruscinski, A., Kobilka, B., and Kandel, E. R. (1999). "ERK plays a regulatory role in induction of LTP by theta frequency stimulation and its modulation by beta-adrenergic receptors." Neuron 24:715-726.
4. Raymond, L. A., Tingley, W. G., Blackstone, C. D., Roche, K. W., and Huganir, R. L. (1994). "Glutamate receptor modulation by protein phosphorylation." J. Physiol. Paris 88:181-192.
5. Suzuki, T., and Okumura-Noji, K. (1995). "NMDA receptor subunits epsilon 1 (NR2A) and epsilon 2 (NR2B) are substrates for Fyn in the postsynaptic density fraction isolated from the rat brain." Biochem. Biophys. Res. Commun. 216:582-588.
6. Zheng, F., Gingrich, M. B., Traynelis, S. F., and Conn, P. J. (1998). "Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc inhibition." Nat. Neurosci. 1:185-191.
7. Lu, Y. M., Roder, J. C., Davidow, J., and Salter, M. W. (1998). "Src activation in the induction of long-term potentiation in CA1 hippocampal neurons." Science 279:1363-1367.
8. Huang, Y., Lu, W., Ali, D. W., Pelkey, K. A., Pitcher, G. M., Lu, Y. M., Aoto, H., Roder, J. C., Sasaki, T., Salter, M. W., and MacDonald, J. F.
(2001). "CAKbeta/Pyk2 kinase is a signaling link for induction of long-term potentiation in CA1 hippocampus." Neuron 29:485-496.
9. Grosshans, D. R., and Browning, M. D. (2001). "Protein kinase C activation induces tyrosine phosphorylation of the NR2A and NR2B subunits of the NMDA receptor." J. Neurochem. 76:737-744.
10. Takasu, M. A., Dalva, M. B., Zigmond, R. E., and Greenberg, M. E. (2002). "Modulation of NMDA receptor-dependent calcium influx and gene expression through EphB receptors." Science 295:491-495.
11. Grunwald, I. C., Korte, M., Wolfer, D., Wilkinson, G. A., Unsicker, K., Lipp, H. P., Bonhoeffer, T., and Klein, R. (2001). "Kinase-Independent Requirement of EphB2 Receptors in Hippocampal Synaptic Plasticity." Neuron 32:1027-1040.
12. Henderson, J. T., Georgiou, J., Jia, Z., Robertson, J., Elowe, S., Roder, J. C., and Pawson, T. (2001). "The Receptor Tyrosine Kinase EphB2 Regulates
NMDA-Dependent Synaptic Function." Neuron 32:1041-1056.
13. Shanley, L. J., Irving, A. J., and Harvey, J. (2001). "Leptin enhances NMDA receptor function and modulates hippocampal synaptic plasticity." J. Neurosci. 21:RC186.
14. Yaka, R., Thornton, C., Vagts, A. J., Phamluong, K., Bonci, A., and Ron, D. (2002). "NMDA receptor function is regulated by the inhibitory scaffolding protein, RACK1." Proc. Natl. Acad. Sci. USA 99:5710-5715.
15. Liao, G. Y., Kreitzer, M. A., Sweetman, B. J., and Leonard, J. P. (2000). "The postsynaptic density protein PSD-95 differentially regulates insulin-and Src-mediated current modulation of mouse NMDA receptors expressed in Xenopus oocytes." J. Neurochem. 75:282-287.
16. Logan, S. M., Rivera, F. E., and Leonard, J. P. (1999). "Protein kinase C modulation of recombinant NMDA receptor currents: roles for the C-terminal C1 exon and calcium ions." J. Neurosci. 19:974-986.
17. Liao, G. Y., Wagner, D. A., Hsu, M. H., and Leonard, J. P. (2001). "Evidence for direct protein kinase-C mediated modulation of N-methyl-D-aspartate receptor current." Mol. Pharmacol. 59:960-964.
18. Ben-Ari, Y., Aniksztejn, L., and Bregestovski, P. (1992). "Protein kinase C modulation of NMDA currents: an important link for LTP induction." Trends Neurosci. 15:333-339.
19. Westphal, R. S., Tavalin, S. J., Lin, J. W., Alto, N. M., Fraser, I. D., Langeberg, L. K., Sheng, M., and Scott, J. D. (1999). "Regulation of NMDA receptors by an associated phosphatase-kinase signaling complex." Science 285:93-96.
20. Fischer, A., Sananbenesi, F., Schrick, C., Spiess, J., and Radulovic, J. (2002). "Cyclin-dependent kinase 5 is required for associative learning." J. Neurosci. 22:3700-3707.
21. Li, B. S., Sun, M. K., Zhang, L., Takahashi, S., Ma, W., Vinade, L., Kulkarni, A. B., Brady, R. O., and Pant, H. C. (2001). "Regulation of NMDA receptors by cyclin-dependent kinase-5." Proc. Natl. Acad. Sci. USA 98:12742-12747.
22. Choi, Y. B., Tenneti, L., Le, D. A., Ortiz, J., Bai, G., Chen, H. S., and Lipton, S. A. (2000). "Molecular basis of NMDA receptor-coupled ion channel modulation by S-nitrosylation." Nat. Neurosci. 3:15-21.
23. Choi, Y. B., and Lipton, S. A. (2000). "Redox modulation of the NMDA receptor." Cell. Mol. Life Sci. 57:1535-1541.
24. Traynelis, S. F., Hartley, M., and Heinemann, S. F. (1995). "Control of proton sensitivity of the NMDA receptor by RNA splicing and polyamines." Science 268:873-876.
25. Gallagher, M. J., Huang, H., Grant, E. R., and Lynch, D. R. (1997). "The NR2B-specific interactions of polyamines and protons with the N-methyl-D-aspartate receptor." J. Biol. Chem. 272:24971-24979.
26. Lieberman, D. N., and Mody, I. (1999). "Casein kinase-II regulates NMDA channel function in hippocampal neurons." Nat. Neurosci. 2:125-132.
27. Charriaut-Marlangue, C., Otani, S., Creuzet, C., Ben-Ari, Y., Loeb, J. (1991). "Rapid activation of hippocampal casein kinase II during long-term potentiation." Proc. Natl. Acad. Sci. USA 88:10232-10236.
28. Ingi, T., Worley, P. F., and Lanahan, A. A. (2001) "Regulation of SSAT expression by synaptic activity." Eur. J. Neurosci. 13:1459-1463.
29. Stuart, G. J., and Sakmann, B. (1994). "Active propagation of somatic action potentials into neocortical pyramidal cell dendrites." Nature 367:69-72.
30. Spruston, N., Schiller, Y., Stuart, G., and Sakmann, B. (1995). "Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites." Science 268:297-300.
31. Magee, J. C., and Johnston, D. (1995). "Synaptic activation of voltage-gated channels in the dendrites of hippocampal pyramidal neurons." Science 268:301-304.
32. Hoffman, D. A., Magee, J. C., Colbert, C. M., and Johnston, D. (1997). "K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons." Nature 387:869-875.
33. Yuan, L. L., Adams, J. P., Swank, M., Sweatt, J. D., and Johnston, D. (2002). "Protein kinase modulation of dendritic K+ channels in hippocampus involves a mitogen-activated protein kinase pathway." J. Neurosci. 22:4860-4868.
34. Watanabe, S., Hoffman, D. A., Migliore, M., and Johnston, D. (2002). "Dendritic K+ channels contribute to spike-timing dependent long-term potentiation in hippocampal pyramidal neurons." Proc. Natl. Acad. Sci. USA 99:8366-8371.
35. Adams, J. P., Anderson, A. E., Varga, A. W., Dineley, K. T., Cook, R. G., Pfaffinger, P. J., and Sweatt, J. D. (2000). "The A-type potassium channel Kv4.2 is a substrate for the mitogen-activated protein kinase ERK." J. Neurochem. 2000, 75:2277-2287.
36. Magee, J. C. (1998). "Dendritic hyperpolarization-activated currents modify the integrative properties of hippocampal CA1 pyramidal neurons." J. Neurosci. 18:7613-7624.
37. Colbert, C. M., and Johnston, D. (1998). "Protein kinase C activation decreases activity-dependent attenuation of dendritic Na+ current in hippocam-pal CA1 pyramidal neurons." J. Neurophysiol. 79:491-495.
38. Tsubokawa, H. (2000). "Control of Na+ spike backpropagation by intracellular signaling in the pyramidal neuron dendrites." Mol. Neurobiol. 22:129-141.
39. Andreasen, M., and Nedergaard, S. (1996). "Dendritic electrogenesis in rat hippocampal CA1 pyramidal neurons: functional aspects of Na+ and Ca2+ currents in apical dendrites." Hippocampus 6:79-95.
40. Martin, K. H., Slack, J. K., Boerner, S. A., Martin, C. C., and Parsons, J. T. (2002). "Integrin connections map: to infinity and beyond." Science 296:1652-1653.
41. Davis, R., and Weeber, E. J. (2001): Personal Communication.
42. Lauri, S. E., Kaukinen, S., Kinnunen, T., Ylinen, A., Imai, S., Kaila, K., Taira, T., and Rauvala, H. (1999). "Regulatory role and molecular interactions of a cell-surface heparan sulfate proteoglycan (N-syndecan) in hippocampal long-term potentiation." J. Neurosci. 19:1226-1235.
43. Bliss, T., Errington, M., Fransen, E., Godfraind, J. M., Kauer, J. A., Kooy, R. F., Maness, P. F., and Furley, A. J. (2000). "Long-term potentiation in mice lacking the neural cell adhesion molecule L1." Curr. Biol. 10:1607-1610.
44. Holst BD, Vanderklish PW, Krushel LA, Zhou W, Langdon RB, McWhirter JR, Edelman GM, Crossin KL: "Allosteric modulation of AMPA-type glutamate receptors increases activity of the promoter for the neural cell adhesion molecule, N-CAM." Proc. Natl. Acad. Sci. USA 1998, 95:2597-2602.
45. Luthl, A., Laurent, J. P., Figurov, A., Muller, D., and Schachner, M. (1994). "Hippocampal long-term potentiation and neural cell adhesion molecules L1 and NCAM." Nature 372:777-779.
46. Huntley, G. W., Gil, O., and Bozdagi, O. (2002). "The cadherin family of cell adhesion molecules: multiple roles in synaptic plasticity." Neuroscientist 8:221-233.
47. Sheng, M., and Pak, D. T. (2000). "Ligand-gated ion channel interactions with cytoskeletal and signaling proteins." Annu. Rev. Physiol. 62:755-778.
48. Sheng, M. (2001). "Molecular organization of the postsynaptic specialization." Proc. Natl. Acad. Sci. USA 98:7058-7061.
49. Migaud, M., Charlesworth, P., Dempster, M., Webster, L. C., Watabe, A. M., Makhinson, M., He, Y., Ramsay, M. F., Morris, R. G., Morrison, J. H., O'Dell, T. J., and Grant, S. G. (1998). "Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein." Nature 396:433-439.
50. Sprengel, R., Suchanek, B., Amico, C., Brusa, R., Burnashev, N., Rozov, A., Hvalby, O., Jensen, V., Paulsen, O., Andersen, P., Kim, J. J., Thompson, R. F., Sun, W., Webster, L. C., Grant, S. G., Eilers, J., Konnerth, A., Li, J., McNamara, J. O., and Seeburg, P. H. (1998). "Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo." Cell. 92:279-289.
51. Passafaro, M., Piech, V., and Sheng, M. (2001). "Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons." Nat. Neurosci. 4:917-926.
52. Sweatt, J. D. (2001). "Protooncogenes subserve memory formation in the adult CNS." Neuron 31:671-674.
53. Vetter, I. R., and Wittinghofer, A. (2001). "The guanine nucleotide-binding switch in three dimensions." Science 294:1299-1304.
54. Colledge, M., Dean, R. A., Scott, G. K., Langeberg, L. K., Huganir, R. L., and Scott, J. D. (2000). "Targeting of PKA to glutamate receptors through a MAGUK-AKAP complex." Neuron 27:107-119.
55. Coghlan, V. M., Perrino, B. A., Howard, M., Langeberg, L. K., Hicks, J. B., Gallatin, W. M., and Scott, J. D. (1995). "Association of protein kinase A and protein phosphatase 2B with a common anchoring protein." Science 267:108-111.
56. Dodge, K., and Scott, J. D. (2000). "AKAP79 and the evolution of the AKAP model." FEBS Lett. 476:58-61.
57. Tavalin, S. J., Colledge, M., Hell, J. W., Langeberg, L. K., Huganir, R. L., and Scott, J. D. (2002). "Regulation of GluR1 by the A-kinase anchoring protein 79 (AKAP79) signaling complex shares properties with long-term depression." J. Neurosci. 22:3044-3051.
58. Sabatini, B. L., Oertner, T. G., and Svoboda, K. (2002). "The life cycle of Ca(2+) ions in dendritic spines." Neuron 33:439-452.
59. Wheeler, D. B., Randall, A., and Tsien, R. W. (1994). "Roles of N-type and Q-type Ca2+ channels in supporting hippocampal synaptic transmission." Science 264:107-111.
60. Huang, Y. Y., and Malenka, R. C. (1993). "Examination of TEA-induced synaptic enhancement in area CA1 of the hippocampus: the role of voltage-dependent Ca2+ channels in the induction of LTP." J. Neurosci. 13:568-576.
61. Morgan, S. L., and Teyler, T. J. (1999). "VDCCs and NMDARs underlie two forms of LTP in CA1 hippocampus in vivo." J. Neurophysiol. 82:736-740.
62. Ito, K., Miura, M., Furuse, H., Zhixiong, C., Kato, H., Yasutomi, D., Inoue, T., Mikoshiba, K., Kimura, T., Sakakibara, S., and Miyakawa, H. (1995). "Voltage-gated Ca2+ channel blockers, omega-AgaIVA and Ni2+, suppress the induction of theta-burst induced long-term potentiation in guinea-pig hippocampal CA1 neurons." Neurosci. Lett. 183:112-115.
63. Dudek, S. M., and Fields, R. D. (2001). "Mitogen-activated protein kinase/extracellular signal-regulated kinase activation in somatoden-dritic compartments: roles of action potentials, frequency, and mode of calcium entry." J. Neurosci. 21:RC122.
64. Magee, J. C., and Johnston, D. (1997). "A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons." Science 275:209-213.
65. Chetkovich, D. M., Gray, R., Johnston, D., and Sweatt, J. D. (1991). "N-methyl-D-aspartate receptor activation increases cAMP levels and voltage-gated Ca2+ channel activity in area CA1 of hippocampus." Proc. Natl. Acad. Sci. USA 88:6467-6471.
66. Johenning, F. W., and Ehrlich, B. E. (2002). "Signaling microdomains: InsP(3) receptor localization takes on new meaning." Neuron 34:173-175.
67. Emptage, N., Bliss, T. V., and Fine, A. (1999). "Single synaptic events evoke NMDA receptor-mediated release of calcium from internal stores in hip-pocampal dendritic spines." Neuron 22:115-124.
68. Behnisch, T., and Reymann, K. G. (1995). "Thapsigargin blocks long-term potentiation induced by weak, but not strong tetanisation in rat hippocampal CA1 neurons." Neurosci. Lett. 192:185-188.
69. Harvey, J., and Collingridge, G. L. (1992). "Thapsigargin blocks the induction of long-term potentiation in rat hippocampal slices." Neurosci. Lett. 139:197-200.
70. Balschun, D., Wolfer, D. P., Bertocchini, F., Barone, V., Conti, A., Zuschratter, W., Missiaen, L., Lipp, H. P., Frey, J. U., and Sorrentino, V. (1999). "Deletion of the ryanodine receptor type 3 (RyR3) impairs forms of synaptic plasticity and spatial learning." Embo.J. 18:5264-5273.
71. Shimuta, M., Yoshikawa, M., Fukaya, M., Watanabe, M., Takeshima, H., and Manabe, T. (2001). "Postsynaptic modulation of AMPA receptor-mediated synaptic responses and LTP by the type 3 ryanodine receptor." Mol. Cell. Neurosci. 17:921-930.
72. Nishiyama, M., Hong, K., Mikoshiba, K., Poo, M. M., and Kato, K. (2000). "Calcium stores regulate the polarity and input specificity of synaptic modification." Nature 408:584-588.
73. Futatsugi, A., Kato, K., Ogura, H., Li, S. T., Nagata, E., Kuwajima, G., Tanaka, K., Itohara, S., and Mikoshiba, K. (1999). "Facilitation of NMDAR-independent LTP and spatial learning in mutant mice lacking ryanodine receptor type 3." Neuron 24:701-713.
74. Fujii, S., Matsumoto, M., Igarashi, K., Kato, H., and Mikoshiba, K. (2000). "Synaptic plasticity in hippocampal CA1 neurons of mice lacking type 1 inositol-1,4,5-trisphosphate receptors." Learn. Mem. 7:312-320.
75. Weeber, E. J., Levy, M., Sampson, M. J., Anflous, K., Armstrong, D. L., Brown, S. E., Sweatt, J. D., and Craigen, W. J. (2002). "The role of mitochondrial porins and the permeability transition pore in learning and synaptic plasticity." J. Biol. Chem. 277:18891-18897.
76. Levy, M. (2002). Personal Communication.
77. Blitzer, R. D., Connor, J. H., Brown, G. P., Wong, T., Shenolikar, S., Iyengar, R., and Landau, E. M. (1998). "Gating of CaMKII by cAMP-regulated protein phosphatase activity during LTP." Science 280:1940-1942.
78. Winder, D. G., and Sweatt, J. D. (2001). "Roles of serine/threonine phosphatases in hippocampal synaptic plasticity." Nat. Rev. Neurosci. 2:461-474.
79. Giovannini, M. G., Blitzer, R. D., Wong, T., Asoma, K., Tsokas, P., Morrison, J. H., Iyengar, R., and Landau, E. M. (2001). "Mitogen-activated protein kinase regulates early phosphorylation and delayed expression of Ca2+/calmodulin-dependent protein kinase II in long-term potentiation." J. Neurosci. 21:7053-7062.
80. 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.
81. Malleret, G., Haditsch, U., Genoux, D., Jones, M. W., Bliss, T. V., Vanhoose, A. M., Weitlauf, C., Kandel, E. R., Winder, D. G., and Mansuy, I. M. (2001). "Inducible and reversible enhancement of learning, memory, and long-term potentiation by genetic inhibition of calcineurin." Cell. 104:675-686.
82. Gerendasy, D. D., and Sutcliffe, J. G. (1997). "RC3/ neurogranin, a postsynaptic calpacitin for setting the response threshold to calcium influxes." Mol. Neurobiol. 15:131-163.
83. Ramakers, G. M., Pasinelli, P., van Beest, M., van der Slot, A., Gispen, W. H., and De Graan, P. N. (2000). "Activation of pre- and postsynaptic protein kinase C during tetraethylammonium-induced long-term potentiation in the CA1 field of the hippocampus." Neurosci. Lett. 286:53-56.
84. Chen, S. J., Sweatt, J. D., and Klann, E. (1997). "Enhanced phosphorylation of the postsynaptic protein kinase C substrate RC3/neurogranin during long-term potentiation." Brain Res. 749:181-187.
85. Ramakers, G. M., Gerendasy, D. D., and de Graan, P. N. (1999). "Substrate phosphorylation in the protein kinase Cgamma knockout mouse." J. Biol. Chem. 274:1873-1874.
86. Krucker, T., Siggins, G. R., McNamara, R. K., Lindsley, K. A., Dao, A., Allison, D. W.,
De Lecea, L., Lovenberg, T. W., Sutcliffe, J. G., and Gerendasy, D. D. (2002). "Targeted disruption of RC3 reveals a calmodulin-based mechanism for regulating metaplasticity in the hippocampus." J. Neurosci. 22:5525-5535.
87. Wu, J., Li, J., Huang, K. P., and Huang, F. L. (2002). "Attenuation of protein kinase C and cAMP-dependent protein kinase signal transduction in the neurogranin knockout mouse." J. Biol. Chem. 277:19498-19505.
88. Wang, J. H., and Kelly, P. T. (1995). "Postsynaptic injection of CA2+/CaM induces synaptic potentiation requiring CaMKII and PKC activity." Neuron 15:443-452.
89. Pak, J. H., Huang, F. L., Li, J., Balschun, D., Reymann, K. G., Chiang, C., Westphal, H., and Huang, K. P. (2000). "Involvement of neurogranin in the modulation of calcium/calmodulin-dependent protein kinase II, synaptic plasticity, and spatial learning: a study with knockout mice." Proc. Natl. Acad. Sci. USA 97:11232-11237.
90. Husi, H., Ward, M. A., Choudhary, J. S., Blackstock, W. P., and Grant, S. G. (2000). "Proteomic analysis of NMDA receptor-adhesion protein signaling complexes." Nat. Neurosci. 3:661-669.
91. Husi, H., and Grant, S. G. (2001). "Proteomics of the nervous system." Trends Neurosci. 2001, 24:259-266.
92. Adams, J. P., and Sweatt, J. D. (2002). "Molecular psychology: roles for the ERK MAP kinase cascade in memory." Annu. Rev. Pharmacol. Toxicol. 42:135-163.
93. Sweatt, J. D. (2001). "Memory mechanisms: the yin and yang of protein phosphorylation." Curr. Biol. 11:R391-394.
94. Weeber, E. J., and Sweatt, J. D. (2002). "Molecular neurobiology of human cognition." Neuron 33:845-848.
Autonomous Kinases in the PSD J. David Sweatt, Acrylic on canvas, 2002
Was this article helpful?
A course in techniques and skills for mentalists, magicians and students. For students, improve your grades with less effort! But this book is also.... The ideal for any stage mentalist or magician by establishing credibility of amazing skills with an easy to follow instructional book on using the amazing power of your memory.