Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-15T21:24:32.689Z Has data issue: false hasContentIssue false
  • English
  • Français

Genetic Approaches to the Study of Synaptic Plasticity and Memory Storage

Published online by Cambridge University Press:  07 November 2014

Ted Abel  and
Michael P. Kaplan
Get access Rights & Permissions [Opens in a new window]

Abstract

Long-term memory is believed to depend on long-lasting changes in the strength of synaptic transmission known as synaptic plasticity. Understanding the molecular mechanisms of long-term synaptic plasticity is one of the principle goals of neuroscience. Among the most powerful tools being brought to bear on this question are genetically modified mice with changes in the expression or biological activity of genes thought to contribute to these processes. This article reviews how strains of mice with alterations in the cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate-response element-binding protein signaling pathway have advanced our understanding of the biological basis of learning and memory.

Type
Review Article
Information
CNS Spectrums , Volume 8 , Issue 8: Genetically Altered Mice in the Study of Neuropsychiatrty , August 2003 , pp. 597 - 610
Copyright
Copyright © Cambridge University Press 2003

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Hebb, DO. Essay on Mind. Hillsdale NJ: Lawrence Erlbaum Associates; 1980.Google Scholar
2.Abel, T, Kandel, E. Positive and negative regulatory mechanisms that mediate long-term memory storage. Brain Res Rev. 1998;26:360–378.CrossRefGoogle ScholarPubMed
3.Abel, T, Nguyen, PV, Barad, M, Deuel, TAS, Kandel, ER, Bourtchouladze R Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory. Cell. 1997;88:615–626.CrossRefGoogle ScholarPubMed
4.Malleret, G, Haditsch, U, Genoux, D, et al.Inducible and reversible enhancement of learning, memory, and long-term potentiation by genetic inhibition of calcineurin. Cell. 2001;104:675–86.CrossRefGoogle ScholarPubMed
5.Winder, DG, Mansuy, IM, Osman, M, Moallem, TM, Kandel, ER. Genetic and pharmacological evidence for a novel, intermediate phase of long-term potentiation suppressed by calcineurin. Cell. 1998;92:25–37.CrossRefGoogle ScholarPubMed
6.Mansuy, IM, Mayford, M, Jacob, B, Kandel, ER, Bach, MERestricted and regulated overexpression reveals calcineurin as a key component in the transition from short-term to long-term memory. Cell. 1998;92:39–49.CrossRefGoogle ScholarPubMed
7.Allen, PB, Hvalby, O, Jensen, V, et al.Protein phosphatase-1 regulation in the induction of long-term potentiation: heterogeneous molecular mechanisms. J Neurosci. 2000;20:3537–3543.CrossRefGoogle ScholarPubMed
8.Genoux, D, Haditsch, U, Knobloch, M, Michalon, A, Storm, D, Mansuy, IM. Protein phosphatase 1 is a molecular constraint on learning and memory. Nature. 2002;418:970–975.CrossRefGoogle ScholarPubMed
9.Bourtchouladze, R, Frenguelli, B, Blendy, J, Cioffi, D, Schütz, G, Silva, AJ. Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell. 1994;79:59–68.CrossRefGoogle Scholar
10.Pittenger, C, Huang, YY, Paletzki, RF, et al.Reversible inhibition of CREB/ATF transcription factors in region CA1 of the dorsal hippocampus disrupts hippocampus-dependent spatial memory. Neuron. 2002;34:447–462.CrossRefGoogle ScholarPubMed
11.Cajal, SR. La fine structure des centres nerveux. Proc R Soc Lond B Biol Sci. 1894;55:444–468.Google Scholar
12.Frost, WN, Castelucci, VF, Hawkins, RD, Kandel, ER. Monosynaptic connections made by the sensory neurons of the gill and siphon withdrawal reflex in Aplysia participate in the storage of long-term memory for sensitization. Proc Natl Acad Sci U S A. 1985;82:8266–8269.CrossRefGoogle Scholar
13.Bartsch, D, Casadio, A, Karl, KA, Serodio, P, Kandel, ER. CREB1 encodes a nuclear activator, a repressor, and a cytoplasmic modulator that form a regulatory unit critical for long-term facilitation. Cell. 1998;95:211–223.CrossRefGoogle Scholar
14.Antonov, I, Kandel, ER, Hawkins, RD. The contribution of facilitation of monosynaptic PSPs to dishabituation and sensitization of the Aplysia siphon withdrawal reflex. J Neurosci. 1999;19:10438–450.CrossRefGoogle ScholarPubMed
15.Montarolo, PG, Goelet, P, Castellucci, VF, Morgan, J, Kandel, ER, Schacher, S. A critical period for macronuclear synthesis in long-term heterosynaptic facilitation in Aplysia. Science. 1986;234:1249–1254.CrossRefGoogle Scholar
16.Dash, P, Hochner, B, Kandel, ER. Injection of the cAMP-responsive element into the nucleus of Aplysia sensory neurons blocks long-term facilitation. Nature. 1990;345:718–721.CrossRefGoogle ScholarPubMed
17.Mayr, B, Montminy, M. Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat Rev Mol Cell Biol. 2001;2:599–609.CrossRefGoogle ScholarPubMed
18.Lonze, B, Ginty, D. Function and regulation of CREB family transcription factors in the nervous system. Neuron. 2002;35:605–623.CrossRefGoogle ScholarPubMed
19.Guan, Z, Giustetto, M, Lomvardas, S, et al.Integration of long-term-memory-related synaptic plasticity involves bidirectional regulation of gene expression and chromatin structure. Cell. 2002;111:483–493.CrossRefGoogle ScholarPubMed
20.Weiner, J. Time, Love, Memory: A Great Biologist and His Quest for the Origins of Behavior. New York, NY: Alfred A. Knopf; 1999.Google Scholar
21.Tully, T. Drosophila learning: behavior and biochemistry. Behav Genet. 1984;14:527–557.CrossRefGoogle ScholarPubMed
22.Dubnau, J, Tully, T. Gene discovery in Drosophila: new insights for learning and memory. Annu Rev Neurosci. 1998;21:407–444.CrossRefGoogle ScholarPubMed
23.Livingstone, MS, Sziber, PP, Quinn, WG. Loss of calcium/calmodulin responsiveness in adenylate cyclase of rutabaga, a Drosophila learning mutant. Cell. 1984;37:205–215.CrossRefGoogle ScholarPubMed
24.Levin, LR, Han, PL, Hwang, PM, Feinstein, PG, Davis, RL, Reed, RR. The Drosophila learning and memory gene rutabaga encodes a Ca2+/Calmodulin-responsive adenylyl cyclase. Cell. 1992;68:479–489.CrossRefGoogle ScholarPubMed
25.Byers, D, Davis, RL, Kiger, JA Jr.Defect in cyclic AMP phosphodiesterase due to the dunce mutation of learning in Drosophila melanogaster. Nature. 1981;289:79–81.CrossRefGoogle Scholar
26.Chen, CN, Denome, S, Davis, RLMolecular analysis of cDNA clones and the corresponding genomic coding sequences of the Drosophila dunce+ gene, the structural gene for cAMP phosphodiesterase. Proc Nad Acad Sci U S A 1986;83:9313–9317.CrossRefGoogle ScholarPubMed
27.Dudai, Y, Jan, YN, Byers, D, Quinn, WG, Benzer, S. Dunce, a mutant of Drosophila deficient in learning. Proc Natl Acad Sci U S A. 1976;73:1684–1688.CrossRefGoogle ScholarPubMed
28.Yin, JC, Wallach, JS, Del Vecchio, M, et al.Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila. Cell. 1994;79:49–58.CrossRefGoogle ScholarPubMed
29.Yin, JCP, Del Vecchio, M, Zhou, H, Tully, T. CREB as a memory modulator: Induced expression of a dCREB2 activator isoform enhances long-term memory in Drosophila. Cell. 1995;81:107–115.CrossRefGoogle ScholarPubMed
30.Milner, B, Scoville, WB. Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry. 1957;20:11–21.Google Scholar
31.Milner, B, Squire, LR, Kandel, ER. Cognitive neuroscience and the study of memory. Neuron. 1998;20:445–468.CrossRefGoogle Scholar
32.Morris, RGM, Garrud, P, Rawlins, JNP, O'Keefe, J. Place navigation impaired in rats with hippocampal lesions. Nature. 1982;297:681–683.CrossRefGoogle ScholarPubMed
33.Logue, SF, Paylor, R, Wehner, JM. Hippocampal lesions cause learning deficits in inbred mice in the Morris water maze and conditioned fear task. Behav Neurosci. 1997;111:104–113.CrossRefGoogle ScholarPubMed
34.Bliss, TV, Lomo, T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol. 1973;232:331–356.CrossRefGoogle ScholarPubMed
35.Huang, Y-Y, Nguyen, PV, Abel, T, Kandel, ER. Long-lasting forms of synaptic potentiation in the mammalian hippocampus. Learn Mem. 1996;3:74–85.CrossRefGoogle ScholarPubMed
36.Martin, SJ, Grimwood, PD, Morris, RG. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci. 2000;23:649–711.CrossRefGoogle ScholarPubMed
37.Matynia, A, Kushner, SA, Silva, AJ. Genetic approaches to molecular and cellular cognition. Ann Rev Genet. 2002;36:687–720.CrossRefGoogle ScholarPubMed
38.Bliss, TV, Collingridge, GL.. A synaptic model of memory: Long-term potentiation in the hippocampus. Nature. 1993;361:31–39.CrossRefGoogle ScholarPubMed
39.Frey, U, Krug, M, Reymann, KG, Matthies, H. Anisomycin, an inhibitor of protein synthesis, blocks late phase of LTP phenomena in the hippocampal CA1 region in vitro. Brain Res. 1988;452:57–65.CrossRefGoogle ScholarPubMed
40.Frey, U, Huang, Y-Y, Kandel, ER. Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. Science. 1993;260:1661–1664.CrossRefGoogle ScholarPubMed
41.Huang, Y-Y, Kandel, ERRecruitment of long-lasting and protein kinase A-dependent long-term potentiation in the CA1 region of hippocampus requires repeated tetanization. Learn Mem. 1994;1:74–82.CrossRefGoogle ScholarPubMed
42.Huang, Y-Y, Li, X-C, Kandel, ER. cAMP contributes to mossy fiber LTP by initiating both a covalently-mediated early phase and a macromolecular synthesis-dependent late phase. Cell. 1994;79:69–80.CrossRefGoogle Scholar
43.Nguyen, PV, Abel, T, Kandel, ER. Requirement for a critical period of transcription for induction of a late phase of LTP. Science. 1994;265:1104–1107.CrossRefGoogle ScholarPubMed
44.Duffy, SN, Craddock, KJ, Abel, T, Nguyen, PV. Environmental enrichment modifies the PKA-dependence of hippocampal LTP and improves hippocampus-dependent memory. Learn Mem. 2001;8:26–34.CrossRefGoogle ScholarPubMed
45.Duffy, SN, Nguyen, PV. Postsynaptic application of a peptide inhibitor of cAMP-dependent protein kinase blocks expression of long-lasting synaptic potentiation in hippocampal neurons. J Neurosci. 2003;23:1142–1150.CrossRefGoogle ScholarPubMed
46.Woo, NH, Duffy, SN, Abel, T, Nguyen, PV. Temporal spacing of synaptic stimulation critically modulates the dependence of LTP on cyclic AMP-dependent protein kinase. Hippocampus. 2003;13:251–258.CrossRefGoogle ScholarPubMed
47.Frey, U, Frey, S, Schollmeier, F, Krug, M. Influence of actinomycin D, a RNA synthesis inhibitor, on long-term potentiation in rat hippocampal neurons in vivo and in vitro. J Physiol (Lond). 1996;490(pt 3):703–711.CrossRefGoogle ScholarPubMed
48.Davis, HP, Squire, LR. Protein synthesis and memory: A review. Psychol Bull. 1984;96:518–559.CrossRefGoogle ScholarPubMed
49.Bourtchouladze, R, Abel, T, Berman, N, Gordon, R, Lapidus, K, Kandel, ER. Different training procedures for contextual memory in mice can recruit either one or two critical periods for memory consolidation that require protein synthesis and PKA. Learn Mem. 1998;5:365–374.CrossRefGoogle ScholarPubMed
50.Sanes, JR, Lichtman, JW. Can molecules explain long-term potentiation? Nat Neurosci. 1999;2:597–604.CrossRefGoogle ScholarPubMed
51.Malenka, RC, Nicoll, RA. Long-term potentiation—a decade of progress? Science. 1999;285:1870–1874.CrossRefGoogle ScholarPubMed
52.Impey, S, Mark, M, Villacres, EC, Poser, S, Chavkin, C, Storm, DR. Induction of CRE-mediated gene expression by stimuli that generate long-lasting LTP in area CA1 of the hippocampus. Neuron. 1996;16:973–982.CrossRefGoogle ScholarPubMed
53.Impey, S, Smith, DM, Obrietan, K, Donahue, R, Wade, C, Storm, DR. Stimulation of cAMP response element (CRE)-mediated transcription during contextual learning. Nat Neurosci. 1998;1:595–601.CrossRefGoogle ScholarPubMed
54.Frey, U, Morris, RGM. Synaptic tagging and long-term potentiation. Nature. 1997;385:533–536.CrossRefGoogle ScholarPubMed
55.Frey, U, Morris, RG. Synaptic tagging: implications for late maintenance of hippocampal long- term potentiation. Trends Neurosci. 1998;21:181–8.CrossRefGoogle ScholarPubMed
56.Barco, A, Alarcon, JM, Kandel, ER. Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture. Cell. 2002;108:689–703.CrossRefGoogle ScholarPubMed
57.Smith, WB, Aakalu, G, Schuman, EM. Local protein synthesis in neurons. Curr Biol. 2001;11:R901–R903.CrossRefGoogle ScholarPubMed
58.Steward, O, Schuman, EM. Protein synthesis at synaptic sites on dendrites. Annu Rev Neurosci. 2001;24:299–325.CrossRefGoogle ScholarPubMed
59.Tang, SJ, Reis, G, Kang, H, Gingras, AC, Sonenberg, N, Schuman, EM. A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus. Proc Natl Acad Sci U S A. 2002;99:467–472.CrossRefGoogle ScholarPubMed
60.Blendy, JA, Kaestner, KH, Schmid, W, Gass, P, Schutz, G. Targeting of the CREB gene leads to up-regulation of a novel CREB mRNA isoform. EMBO J. 1996;151098-1106.Google Scholar
61.Amieux, PS, Cummings, DE, Motamed, K, et al.Compensatory regulation of Rlalpha protein levels in protein kinase A mutant mice. J Biol Chem. 1997;272:3993–3999.CrossRefGoogle Scholar
62.Howe, DG, Wiley, JC, McKnight, GS. Molecular and behavioral effects of a null mutation in all PKA C beta isoforms. Mol Cell Neurosci. 2002;20:515–524.CrossRefGoogle Scholar
63.Gass, P, Wolfer, DP, Balschun, D, et al.Deficits in memory tasks of mice with CREB mutations depend on gene dosage. Learn Mem. 1998;5:274–288.CrossRefGoogle ScholarPubMed
64.Graves, L, Dalvi, A, Lucki, I, Blendy, JA, Abel, T. Behavioral analysis of CREB alphadelta mutation on a B6/129 F1 hybrid background. Hippocampus. 2002;12:18–26.CrossRefGoogle ScholarPubMed
65.Mansuy, IM, Bujard, H. Tetracycline-regulated gene expression in the brain. Curr Opin Neurobiol. 2000;10:593–596.CrossRefGoogle ScholarPubMed
66.Sauer, B. Inducible gene targeting in mice using the Cre/lox system. Methods. 1998;14:381–392.CrossRefGoogle ScholarPubMed
67.Abel, T, Lattal, KM. Molecular mechanisms of memory acquisition, consolidation and retrieval. Curr Opin Neurobiol. 2001;11:180–187.CrossRefGoogle ScholarPubMed
68.Scott, JD, Soderling, TRSerine/threonine protein kinases. Curr Opin Neurobiol. 1992;2:289–295.CrossRefGoogle ScholarPubMed
69.Beebe, SJ. The cAMP-dependent protein kinase and cAMP signal transduction. Sem Cancer Biology. 1994;5:285–294.Google ScholarPubMed
70.Brandon, EP, Idzerda, RL, McKnight, GS. PKA isoforms, neural pathways, and behaviour: making the connection. Curr Opin Neurobiol. 1997;7:397–403.CrossRefGoogle ScholarPubMed
71.Huang, Y-Y, Kandel, ER, Varshavsky, L, et al.A genetic test of the effect of mutations in PKA on mossy fiber LTP and its relation to spatial and contextual learning. Cell. 1995;83:1211–1222.CrossRefGoogle ScholarPubMed
72.Qi, M, Zhuo, M, Skälhegg, BS, et al.Impaired hippocampal plasticity in mice lacking the Cb1 catalytic subunit of cAMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1996;93:1571–1576.CrossRefGoogle Scholar
73.Mayford, M, Baranes, D, Podsypanina, K, Kandel, ER. The 3' untranslated region of CaMKIIa in a cis-acting signal for the localization and translation of mRNA in dendrites. Proc Natl Acad Sci U S A. 1996;93:13250–13255.CrossRefGoogle Scholar
74.Scharf, MT, Woo, NH, Lattal, KM, Young, JZ, Nguyen, PV, Abel, T. Protein synthesis is required for the enhancement of long-term potentiation and long-term memory by spaced training. J Neurophysiol. 2002;87:2770–2777.CrossRefGoogle ScholarPubMed
75.Woo, NH, Duffy, SN, Abel, T, Nguyen, PV. Genetic and pharmacological demonstration of differential recruitment of cAMP-dependent protein kinases by synaptic activity. J Neurophysiol. 2000;84:2739–2745.CrossRefGoogle ScholarPubMed
76.Reisel, D, Bannerman, DM, Schmitt, WB, et al.Spatial memory dissociations in mice lacking GluR1. Nat Neurosci. 2002;5:868–873.CrossRefGoogle ScholarPubMed
77.LeDoux, JE. Emotion circuits in the brain. Annu Rev Neurosci. 2000;23:155–184.CrossRefGoogle ScholarPubMed
78.Maren, S. Auditory fear conditioning increases CS-elicited spike firing in lateral amygdala neurons even after extensive overtraining. Eur J Neurosci. 2000;124047-4054.Google Scholar
79.Rotenberg, A, Abel, T, Hawkins, RD, Kandel, ER, Muller, RU. Parallel instabilities of long-term potentiation, place cells, and learning caused by decreased protein kinase A activity. J Neurosci. 2000;20:8096–8102.CrossRefGoogle ScholarPubMed
80.Wong, ST, Athos, J, Figueroa, XA, et al.Calcium-stimulated adenylyl cyclase activity is critical for hippocampus-dependent long-term memory and late phase LTP. Neuron. 1999;23:787–798.CrossRefGoogle ScholarPubMed
81.Winder, DG, Sweatt, JD. Roles of serine/threonine phosphatases in hippocampal synaptic plasticity. Nat Rev Neurosci. 2001;2:461–474.CrossRefGoogle ScholarPubMed
82.Mansuy, IM, Winder, DG, Moallem, TM, et al.Inducible and reversible gene expression with the rtTA system for the study of memory. Neuron. 1998;21:257–265.CrossRefGoogle Scholar
83.Barnes, CA. Memory deficits associated with senescence: A neurophysiological and behavioral study in the rat. J Comp Physiol Psychol. 1979;93:74–104.CrossRefGoogle ScholarPubMed
84.Mulkey, RM, Herron, CE, Malenka, RC. An essential role for protein phosphatases in hippocampal long-term depression. Science. 1993;261:1051–1055.CrossRefGoogle ScholarPubMed
85.Mulkey, RM, Endo, S, Shenolikar, S, Malenka, RC. Involvement of a calcineurin/inhibitor-1 phosphatase cascade in hippocampal long-term depression. Nature. 1994;369:486–488.CrossRefGoogle ScholarPubMed
86.Ingebritsen, TS, Cohen, P. Protein phosphatases: properties and role in cellular regulation. Science. 1983;221:331–338.CrossRefGoogle ScholarPubMed
87.Woo, NH, Abel, T, Nguyen, PV. Genetic and pharmacological demonstration of a role for cyclic AMP-dependent protein kinase-mediated suppression of protein phosphatases in gating the expression of late LTP. Eur J Neurosci. 2002;16:1871–1876.CrossRefGoogle ScholarPubMed
88.Woo, NH, Nguyen, PV. “Silent” metaplasticity of the late phase of long-term potentiation requires protein phosphatases. Learn Mem. 2002;9:202–213.CrossRefGoogle ScholarPubMed
89.Lisman, J. A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory. Proc Natl Acad Sci U S A. 1989;86:9574–9578.CrossRefGoogle ScholarPubMed
90.Blitzer, RD, Wong, T, Nouranifar, R, Iyengar, R, Landau, EM. Postsynaptic cAMP pathway gates early LTP in hippocampal CA1 region. Neuron. 1995;15:1403–1414.CrossRefGoogle ScholarPubMed
91.Blitzer, RD, Connor, JH, Brown, GP, et al.Gating of CaMKII by cAMP-regulated protein phosphatase activity during LTP. Science. 1998;280:1940–1942.CrossRefGoogle ScholarPubMed
92.Barbas, H, Gustafson, EL, Greengard, P. Comparison of the immunocytochemical localization of DARPP-32 and I-1 in the amygdala and hippocampus of the rhesus monkey. J Comp Neurol. 1993;334:1–18.CrossRefGoogle ScholarPubMed
93.Gustafson, EL, Girault, JA, Hemmings, HC, Jr, Nairn, AC, Greengard, P. Immunocytochemical localization of phosphatase inhibitor-1 in rat brain. J Comp Neurol. 1991;310:170–188.CrossRefGoogle ScholarPubMed
94.Lowenstein, PR, Shering, AF, MacDougall, LK, Cohen, P. Immunolocalisation of protein phosphatase inhibitor-1 in the cerebral cortex of the rat, cat, and ferret. Brain Res. 1995;676:80–92.CrossRefGoogle Scholar
95.Sakagami, H, Ebina, K, Kondo, H. Localization of phosphatase inhibitor-1 mRNA in the developing and adult rat brain in comparison with that of protein phosphatase-1 mRNAs. Brain Res Mol Brain Res. 1994;25:7–18.CrossRefGoogle ScholarPubMed
96.Hemmings, HCJ. Darpp32, inhibits ppl only when it is phospho. Nature. 1984;310:503–505.CrossRefGoogle Scholar
97.Alberini, CM, Ghirardi, M, Metz, R, Kandel, ER. C/EBP is an immediate early gene required for the consolidation of long-term facilitation in Aplysia. Cell. 1994;76:1099–1114.CrossRefGoogle ScholarPubMed
98.Silva, AJ, Kogan, JH, Frankland, PW, Kida, S. CREB and memory. Annu Rev Neurosci. 1998;21:127–148.CrossRefGoogle ScholarPubMed
99.Hummler, E, Cole, TJ, Blendy, JA, et al.Targeted mutation of the cAMP response element binding protein (CREB) gene: compensation within the CREB/ATF family of transcription factors. Proc Natl Acad Sci U S A. 1994;91:5647–5651.CrossRefGoogle ScholarPubMed
100.Kogan, JH, Frankland, PW, Blendy, JA, et al.Spaced training induces normal long-term memory in CREB mutant mice. Curr Biol. 1997;7:1–11.CrossRefGoogle ScholarPubMed
101.Silva, AJ, Simpson, EM, Joseph, S, et al.Mutant mice and neuroscience: recommendations concerning genetic background. Neuron. 1997;19:755–759.CrossRefGoogle Scholar
102.Bucan, M, Abel, T. The mouse: genetics meets behaviour. Nat Rev Genet. 2002;3:114–123.CrossRefGoogle ScholarPubMed
103.Balschun, D, Mantamadiotis, T, Gass, P, Frey, J-U, Shütz, G. Normal neuronal plasticity in CREB-deficient mouse strains. Paper presented at: Annual Meeting of the Society for Neuroscience; November 5, 2000; New Orleans, La.Google Scholar
104.Walton, KM, Rehfuss, RP, Chrivia, JC, Lochner, JE, Goodman, RH. A dominant repressor of cyclic adenosine 3', 5'-monophosphate (cAMP)-regulated enhancer-binding protein activity inhibits the cAMP-mediated induction of the somatostatin promoter in vivo. Mol Endocrinol. 1992;6:647–655.Google ScholarPubMed
105.Mayford, M, Bach, ME, Huang, YY, Wang, L, Hawkins, RD, Kandel, ER. Control of memory formation through regulated expression of a CaMKII transgene. Science. 1996;274:1678–1683.CrossRefGoogle ScholarPubMed
106.Kandel, E, Schwartz, JH, Jessel, TM. Principles of Neural Science. 4th ed. New York, NY: McGraw-Hill; 2000:414.Google Scholar
107.Aaron, GB, Dichter, MA. Excitatory synapses from CA3 pyramidal cells onto neighboring pyramidal cells differ from those onto inhibitory interneurons. Synapse. 2001;42:199–202.CrossRefGoogle ScholarPubMed
108.Shumyatsky, GP, Tsvetkov, E, Malleret, G, et al.Identification of a signaling network in lateral nucleus of amygdala important for inhibiting memory specifically related to learned fear. Cell. 2002;111:905–918.CrossRefGoogle ScholarPubMed
109.Kida, S, Josselyn, SA, de Ortiz, SP, et al.CREB required for the stability of new and reactivated fear memories. Nature Neurosci. 2002;5:348–35.CrossRefGoogle ScholarPubMed
110.McGuire, SE, Le, PT, Davis, RL. The role of Drosophila mushroom body signaling in olfactory memory.[comment]. Science. 2001;293:1330–1333.CrossRefGoogle ScholarPubMed
111.Dubnau, J, Grady, L, Kitamoto, T, Tully, T. Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory [comment]. Nature. 2001;411:476–480.CrossRefGoogle Scholar
112.Hubel, DH, Wiesel, TN, Levay, S. Plasticity of ocular dominance columns in monkey striate cortex. Philos Trans R Soc Land B Biol Sci. 1977;278:377–409.Google ScholarPubMed
113.Gross, C, Zhuang, X, Stark, K, et al.Serotonin 1A receptor acts during development to establish normal anxiety-like behaviour in the adult [comment]. Nature. 2002;416:396–400.CrossRefGoogle Scholar
114.Jones, KL. Smith's Recognizable Patterns of Human Malformation. 4th ed. Philadelphia, PA: W.B. Saunders; 1997.Google Scholar
115.Oike, Y, Hata, A, Mamiya, T, et al.Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice: implications for a dominant-negative mechanism. Hum Mol Genet. 1999;8:387–396.CrossRefGoogle ScholarPubMed
116.Tully, T, Bourtchouladze, R, Scott, R, Tallman, J. Targeting the CREB pathway for memory enhancers. Nat Rev Drug Discov. 2003;2:266–277.CrossRefGoogle ScholarPubMed
117.Small, SA, Wu, EX, Bartsch, D, et al.Imaging physiologic dysfunction of individual hippocampal subregions in humans and genetically modified mice. Neuron. 2000;28:653–664.CrossRefGoogle ScholarPubMed
118.Trachtenberg, JT, Chen, BE, Knott, GW, et al.Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex [comment]. Nature. 2002;420:788–794.CrossRefGoogle ScholarPubMed