CREB, memory enhancement and the treatment of memory disorders: Promises, pitfalls and prospects

Expert Opinion on Therapeutic Targets

Volumn 7, Issue 1, 2003, Pages 101-114

  Barco, Angel ^a   Pittenger, Christopher ^a   Kandel, Eric R ^a  

^a New York Presbyterian Columbia University Medical Center   (United States)

Author keywords

CREB; Learning and memory; Memory enhancement; Neurodegeneration; Transcription regulation

Indexed keywords

CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; GINKGO BILOBA EXTRACT; NICOTINE; TRANSCRIPTION FACTOR AP 1;

AGING; ALZHEIMER DISEASE; COGNITIVE DEFECT; DRUG TARGETING; HUMAN; LEARNING; LONG TERM MEMORY; MAMMAL; MEMORY; MEMORY DISORDER; MENTAL DEFICIENCY; MOLLUSC; NONHUMAN; PLASTICITY; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION;

AMINO ACID SEQUENCE; ANIMALS; ANIMALS, GENETICALLY MODIFIED; APOPTOSIS; CYCLIC AMP; CYCLIC AMP RESPONSE ELEMENT-BINDING PROTEIN; DRUG DESIGN; GENE EXPRESSION REGULATION; HUMANS; LEARNING; LEARNING DISORDERS; MEMORY; MEMORY DISORDERS; MICE; MODELS, BIOLOGICAL; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; NEURONS; NOOTROPIC AGENTS; PROTEIN CONFORMATION; SECOND MESSENGER SYSTEMS;

EID: 0037312865     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728222.7.1.101     Document Type: Review

References (111)

1. HABENER JF, MILLER CP, VALLEJO M: cAMP-dependent regulation of gene transcription by cAMP response element-binding protein and cAMP response element modulator. Vitam. Horm. (1995) 51:1-57.
2. MONTMINY M: Transcriptional regulation by cyclic AMP. Ann. Rev. Biochem. (1997) 66:807-822.
3. DE CESARE D, SASSONE-CORSI P: Transcriptional regulation by cyclic AMP-responsive factors. Prog. Nucleic Acid Res. Mol. Biol. (2000) 64:343-369.
4. MAYR B, MONTMINY M: Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat. Rev. Mol. Cell. Biol. (2001) 2(8):599-609.
5. LONZE BE, GINTY DD: Function and regulation of CREB family transcription factors in the nervous system. Neuron (2002) 35(4):605-623.
6. MONTMINY MR, BILEZIKJIAN LM: Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene. Nature (1987) 328(6126):175-178.
7. MARTIN SJ, GRIMWOOD PD, MORRIS RG: Synaptic plasticity and memory: an evaluation of the hypothesis. Ann. Rev. Neurosci. (2000) 23:649-711.
8. PITTENGER C, KANDEL E: A genetic switch for long-term memory. C. R. Acad. Sci. III (1998) 321(2-3):91-96.
9. NAKAGAWA S, KIM JE, LEE R et al.: Regulation of neurogenesis in adult mouse hippocampus by cAMP and the cAMP response element-binding protein. J. Neurosci. (2002) 22(9):3673-3682.
10. WALTON MR, DRAGUNOW I: Is CREB a key to neuronal survival? Trends Neurosci. (2000) 23(2):48-53.
11. DAWSON TM, GINTY DD: CREB family transcription factors inhibit neuronal suicide. Nat. Med. (2002) 8(5):450-451.
12. PHAM TA, IMPEY S, STORM DR, STRYKER MP: CRE-mediated gene transcription in neocortical neuronal plasticity during the developmental critical period [published erratum appears in Neuron (1999) 22(3):635]. Neuron (1999) 22(1):63-72.
13. NESTLER EJ: Molecular basis of long-term plasticity underlying addiction. Nat. Rev. Neurosci. (2001) 2(2):119-128.
14. GAU D, LEMBERGER T, VON GALL C et al.: Phosphorylation of CREB Ser142 regulates light-induced phase shifts of the circadian clock. Neuron (2002) 34(2):245-253.
15. NESTLER EJ, BARROT M, DILEONE RJ, EISCH AJ, GOLD SJ, MONTEGGIA LM: Neurobiology of depression. Neuron (2002) 34(1):13-25.
16. RADHAKRISHNAN I, PEREZ-ALVARADO GC, PARKER D, DYSON HJ, MONTMINY MR, WRIGHT PE: Solution structure of the KIX domain of CBP bound to the transactivation domain of CREB: a model for activator:coactivator interactions. Cell (1997) 91(6):741-752.
17. PARKER D, JHALA US, RADHAKRISHNAN I et al.: Analysis of an activator:coactivator complex reveals an essential role for secondary structure in transcriptional activation. Mol. Cell (1998) 2(3):353-359.
18. SCHUMACHER MA, GOODMAN RH, BRENNAN RG: The structure of a CREB bZIP.somatostatin CRE complex reveals the basis for selective dimerization and divalent cation-enhanced DNA binding. J. Biol. Chem. (2000) 275(45):35242-35247.
19. DEISSEROTH K, TSIEN RW: Dynamic multiphosphorylation passwords for activity-dependent gene expression. Neuron (2002) 34(2):179-182.
20. HAGIWARA M, ALBERTS A, BRINDLE P et al.: Transcriptional attenuation following cAMP induction requires PP-1-mediated dephosphorylation of CREB. Cell (1992) 70(1):105-113.
21. WADZINSKI BE, WHEAT WH, JASPERS S et al.: Nuclear protein phosphatase 2A dephosphorylates protein kinase A-phosphorylated CREB and regulates CREB transcriptional stimulation. Mol. Cell. Biol. (1993) 13(5):2822-2834.
22. (2+)- and stimulus duration-dependent switch for hippocampal gene expression. Cell (1996) 87(7):1203-1214.
23. SALA C, RUDOLPH-CORREIA S, SHENG M: Developmentally regulated NMDA receptor-dependent dephosphorylation of cAMP response element-binding protein (CREB) in hippocampal neurons. J. Neurosci. (2000) 20(10):3529-3536.
24. HARDINGHAM GE, FUKUNAGA Y, BADING H: Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat. Neurosci. (2002) 5(5):405-414.
25. MERINO A, BUCKBINDER L, MERMELSTEIN FH, REINBERG D: Phosphorylation of cellular proteins regulates their binding to the cAMP response element. J. Biol. Chem. (1989) 264(35):21266-21276.
26. NICHOLS M, WEIH F, SCHMID W et al.: Phosphorylation of CREB affects its binding to high and low affinity sites: implications for cAMP induced gene transcription. EMBO J. (1992) 11(9):3337-3346.
27. RICHARDS JP, BACHINGER HP, GOODMAN RH, BRENNAN RG: Analysis of the structural properties of cAMP-responsive element-binding protein (CREB) and phosphorylated CREB. J. Biol. Chem. (1996) 271(23):13716-13723.
28. WEIH F, STEWART AF, BOSHART M, NITSCH D, SCHUTZ G: In vivo monitoring of a cAMP-stimulated DNA-binding activity. Genes Dev. (1990) 4(8):1437-1449.
29. MAYALL TP, SHERIDAN PL, MONTMINY MR, JONES KA: Distinct roles for P-CREB and LEF-1 in TCR alpha enhancer assembly and activation on chromatin templates in vitro. Genes Dev. (1997) 11(7):887-899.
30. WOLFL S, MARTINEZ C, MAJZOUB JA: Inducible binding of cyclic adenosine 3′,5′-monophosphate (cAMP)-responsive element binding protein (CREB) to a cAMP-responsive promoter in vivo. Mol. Endocrinol. (1999) 13(5):659-669.
31. IGUCHI-ARIGA SM, SCHAFFNER W: CpG methylation of the cAMP-responsive enhancer/promoter sequence TGACGTCA abolishes specific factor binding as well as transcriptional activation. Genes Dev. (1989) 3(5):612-619.
32. CRAIG JC, SCHUMACHER MA, MANSOOR SE, FARRENS DL, BRENNAN RG, GOODMAN RH: Consensus and variant cAMP-regulated enhancers have distinct CREB-binding properties. J. Biol. Chem. (2001) 276(15):11719-11728.
33. CHRIVIA JC, KWOK RP, LAMB N, HAGIWARA M, MONTMINY MR, GOODMAN RH: Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature (1993) 365(6449):855-859.
34. ARIAS J, ALBERTS AS, BRINDLE P et al.: Activation of cAMP and mitogen responsive genes relies on a common nuclear factor. Nature (1994) 370(6486):226-229.
35. KWOK RP, LUNDBLAD JR, CHRIVIA JC et al.: Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature (1994) 370(6486):223-226.
36. PARKER D, FERRERI K, NAKAJIMA T et al.: Phosphorylation of CREB at Ser-133 induces complex formation with CREB-binding protein via a direct mechanism. Mol. Cell. Biol. (1996) 16(2):694-703.
37. CARDINAUX JR, NOTIS JC, ZHANG Q et al.: Recruitment of CREB binding protein is sufficient for CREB-Mediated gene activation. Mol. Cell. Biol. (2000) 20(5):1546-1552.
38. KORNHAUSER JM, COWAN CW, SHAYWITZ AJ et al.: CREB transcriptional activity in neurons is regulated by multiple, calcium-specific phosphorylation events. Neuron (2002) 34(2):221-233.
39. IMPEY S, FONG AL, WANG Y et al.: Phosphorylation of CBP mediates transcriptional activation by neural activity and CaM kinase IV. Neuron (2002) 34(2):235-244.
40. XU W, CHEN H, DU K et al.: A transcriptional switch mediated by cofactor methylation. Science (2001) 294(5551):2507-2511.
41. FIMIA GM, DE CESARE D, SASSONE-CORSI P: CBP-independent activation of CREM and CREB by the LIM-only protein ACT. Nature (1999) 398(6723):165-169.
42. HARDINGHAM GE, ARNOLD FJ, BADING H: Nuclear calcium signaling controls CREB-mediated gene expression triggered by synaptic activity. Nat. Neurosci. (2001) 4(3):261-267.
43. BRUNELLI M, CASTELLUCCI V, KANDEL ER: Synaptic facilitation and behavioral sensitization in Aplysia: possible role of serotonin and cyclic AMP. Science (1976) 194(4270):1178-1181.
44. SCHACHER S, CASTELLUCCI VF, KANDEL ER: cAMP evokes long-term facilitation in Aplysia sensory neurons that requires new protein synthesis. Science (1988) 240(4859):1667-1669.
45. DUDAI Y. JAN YN, BYERS D, QUINN WG, BENZER S: dunce, a mutant of Drosophila deficient in learning. Proc. Natl. Acad. Sci. USA (1976) 73(5):1684-1688.
46. 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(5793):79-81.
47. WADDELL S, QUINN WG: Flies, genes, and learning. Ann. Rev. Neurosci. (2001) 24:1283-1309.
48. DASH PK, HOCHNER B, KANDEL ER: Injection of the cAMP-responsive element into the nucleus of Aplysia sensory neurons blocks long-term facilitation. Nature (1990) 345(6277):718-721.
49. 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(1):49-58.
50. YIN JC, 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(1):107-115.
51. BARTSCH D, GHIRARDI M, SKEHEL PA et al.: Aplysia CREB2 represses long-term facilitation: relief of repression converts transient facilitation into long-term functional and structural change. Cell (1995) 83(6):979-992.
52. BOURTCHULADZE R, FRENGUELLI B, BLENDY J, CIOFFI D, SCHUTZ 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.
53. 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(2):211-223.
54. CASADIO A, MARTIN KC, GIUSTETTO M et al.: A transient, neuron-wide form of CREB-mediated long-term facilitation can be stabilized at specific synapses by local protein synthesis. Cell (1999) 99(2):221-237.
55. HEGDE AN, INOKUCHI K, PEI W et al.: Ubiquitin C-terminal hydrolase is an immediate-early gene essential for long-term facilitation in Aplysia. Cell (1997) 89(1):115-126.
56. 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(6):1099-1114.
57. BARTSCH D, GHIRARDI M, CASADIO A et al.: Enhancement of memory-related long-term facilitation by ApAF, a novel transcription factor that acts downstream from both CREB1 and CREB2. Cell (2000) 103(4):595-608.
58. 2+-stimulated adenylyl cyclases in LTP and memory formation. Int. J. Dev. Neurosci. (2001) 19(4):387-394.
59. LU YF, KANDEL ER, HAWKINS RD: Nitric oxide signaling contributes to late-phase LTP and CREB phosphorylation in the hippocampus. J. Neurosci. (1999) 19(23):10250-10261.
60. DEISSEROTH K, BITO H, TSIEN RW: Signaling from synapse to nucleus: postsynaptic CREB phosphorylation during multiple forms of hippocampal synaptic plasticity. Neuron (1996) 16(1):89-101.
61. TAUBENFELD SM, WIIG KA, BEAR MF, ALBERINI CM: A molecular correlate of memory and amnesia in the hippocampus. Nat. Neurosci. (1999) 2(4):309-310. Letter.
62. 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(5):973-982.
63. 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(7):595-601.
64. 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(4-5):274-288.
65. HUMMLER E, COLE TJ, BLENDY JA et al.: Targeted mutation of the CREB gene: compensation within the CREB/ATF family of transcription factors. Proc. Natl. Acad. Sci. USA (1994) 91(12):5647-5651.
66. 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) 15(5):1098-1106.
67. LONZE BE, RICCIO A, COHEN S, GINTY DD: Apoptosis, axonal growth defects, and degeneration of peripheral neurons in mice lacking CREB. Neuron (2002) 34(3):371-385.
68. QIU J, CAI D, DAI H et al.: Spinal axon regeneration induced by elevation of cyclic AMP. Neuron (2002) 34(6):895-903.
69. NEUMANN S, BRADKE F, TESSIER-LAVIGNE M, BASBAUM AI: Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron (2002) 34(6):885-893.
70. RICCIO A, AHN S, DAVENPORT CM, BLENDY JA, GINTY DD: Mediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neurons. Science (1999) 286(5448):2358-2361.
71. SEE V, BOUTILLIER AL, BITO H, LOEFFLER JP: Calcium/calmodulin-dependent protein kinase Type IV (CaMKIV) inhibits apoprosis induced by potassium deprivation in cerebellar granule neurons. FASEB J. (2001) 15(1):134-144.
72. MANTAMADIOTIS T, LEMBERGER T, BLECKMANN SC et al.: Disruption of CREB function in brain leads to neurodegeneration. Nat. Genet. (2002) 31(1):47-54.
73. FURTH PA, ST ONGE L, BOGER H et al.: Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter. Proc. Natl. Acad. Sci. USA (1994) 91(20):9302-9306.
74. 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(5293):1678-1683.
75. 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(3):447-462.
76. 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(4):647-655.
77. KIDA S, JOSSELYN SA, DE ORTIZ SP et al.: CREB required for the stability of new and reactivated fear memories. Nat. Neurosci. (2002) 5(4):348-355.
78. RAMMES G, STECKLER T, KRESSE A, SCHUTZ G, ZIEGLGANSBERGER W, LUTZ B: Synaptic plasticity in the basolateral amygdala in transgenic mice expressing dominant-negative cAMP response element-binding protein (CREB) in forebrain. Eur. J. Neurosci. (2000) 12(7):2534-2546.
79. 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(5):689-703.
80. FREY U, MORRIS RG: Synaptic tagging and long-term potentiation. Nature (1997) 385(6616):533-536.
81. MARTIN KC, CASADIO A, ZHU H et al.: Synapse-specific, long-term facilitation of Aplysia sensory to motor synapses: a function for local protein synthesis in memory storage. Cell (1997) 91(7):927-938.
82. JOSSELYN SA, SHI C, CARLEZON WA Jr, NEVE RL, NESTLER EJ, DAVIS M: Long-term memory is facilitated by cAMP response element-binding protein overexpression in the amygdala. J. Neurosci. (2001) 21(7):2404-2412.
83. FLOOD JF, CHERKIN A: Fluoxetine enhances memory processing in mice. Psychopharmacology (Berl.) (1987) 93(1):36-43.
84. MCGAUGH JL: Dissociating learning and performance: drug and hormone enhancement of memory storage. Brain Res. Bull. (1989) 23(4-5):339-345.
85. BUCCAFUSCO JJ, JACKSON WJ, TERRY AV Jr, MARSH KC, DECKER MW, ARNERIC SP: Improvement in performance of a delayed matching-to-sample task by monkeys following ABT-418: a novel cholinergic channel activator for memory enhancement. Pychopharmacology (Berl.) (1995) 120(3):256-266.
86. IKARI H, SPANGLER EL, GREIG NH et al.: Maze learning in aged rats is enhanced by phenserine, a novel anticholinesterase. Neuroreport (1995) 6(3):481-484.
87. BARAD M, BOURTCHOULADZE R, WINDER DG, GOLAN H, KANDEL E: Rolipram, a Type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term potentiation and improves memory. Proc. Natl. Acad. Sci. USA (1998) 95(25):15020-15025.
88. BACH ME, BARAD M, SON H et al.: Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway. Proc. Natl. Acad. Sci. USA (1999) 96(9):5280-5285.
89. GOULD TJ, WEHNER JM: Nicotine enhancement of contextual fear conditioning. Behav. Brain Res. (1999) 102(1-2):31-39.
90. ACOSTA GB, BOCCIA MM, BARATTI CM: Gabapentin, an antiepileptic drug, improves memory storage in mice. Neurosci. Lett. (2000) 279(3):173-176.
91. (2+) channel blocker amlodipine facilitates learning and memory in mice. Eur. J. Pharmacol. (2000) 399(1):57-63.
92. LAMIRAULT L, SIMON H: Enhancement of place and object recognition memory in young adult and old rats by RS 67333, a partial agonist of 5-HT4 receptors. Neuropharmacology (2001) 41(7):844-853.
93. GIBBS ME, SUMMERS RJ: Enhancement of memory consolidation in chicks by beta(3)-adrenoceptor agonists. Eur. J. Pharmacol. (2001) 413(2-3):235-240.
94. SOETENS E, D'HOOGE R, HUETING JE: Amphetamine enhances human-memory consolidation. Neurosci. Lett. (1993) 161(1):9-12.
95. INGVAR M, AMBROS-INGERSON J, DAVIS M et al.: Enhancement by an ampakine of memory encoding in humans. Exp. Neurol. (1997) 146(2):553-559.
96. WESNES KA, WARD T. MCGINTY A, PETRINI O: The memory enhancing effects of a Ginkgo biloba/Panax ginseng combination in healthy middle-aged volunteers. Psychopharmacology (Berl.) (2000) 152(4):353-361.
97. REZVANI AH, LEVIN ED: Cognitive effects of nicotine. Biol. Psychiatry (2001) 49(3):258-267.
98. TANG YP, SHIMIZU E, DUBE GR et al.: Genetic enhancement of learning and memory in mice. Nature (1999) 401(6748):63-69. See comments.
99. 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(5):675-686.
100. 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(6901):970-975.
101. CHEN A. Inducible enhancement of memory storage and long-term synaptic plasticity in transgenic mice expressing a dominant-negative inhibitor of ATF-4 and other members of the C/EBP family of transcription factors. Neuron. Submitted.
102. KUROMI H, KIDOKORO Y: Tetanic stimulation recruits vesicles from reserve pool via a cAMP-mediated process in Drosophila synapses. Neuron (2000) 27(1):133-143.
103. MAYFORD M, WANG J, KANDEL ER, O'DELL TJ: CaMKII regulates the frequency-response function of hippocampal synapses for the production of both LTD and LTP. Cell (1995) 81(6):891-904.
104. TSIEN JZ, CHEN DF, GERBER D et al.: Subregion- and cell type-restricted gene knockout in mouse brain. Cell (1996) 87(7):1317-1326. See comments.
105. KANDEL ER, PITTENGER C: The past, the future and the biology of memory storage. Philos. Trans. R. Soc. Lond. B. Biol. Sci. (1999) 354(1352):2027-2052.
106. RAPP PR, GALLAGHER M: Preserved neuron number in the hippocampus of aged rats with spatial learning deficits. Proc. Natl. Acad. Sci. USA (1996) 93(18):9926-9930.
107. MCCAMPBELL A, TAYLOR JP, TAYE AA et al.: CREB-binding protein sequestration by expanded polyglutamine. Hum. Mol. Genet. (2000) 9(14):2197-2202.
108. STEFFAN JS, KAZANTSEV A, SPASIC-BOSKOVIC O et al.: The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl. Acad. Sci. USA (2000) 97(12):6763-6768.
109. NUCIFORA FC Jr, SASAKI M, PETERS ME et al.: Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science (2001) 291(5512):2423-2428.
110. BRAINARD MS, DOUPE AJ: What songbirds teach us about learning. Nature (2002) 417(6886):351-358.
111. SHORS TJ, MIESEGAES G, BEYLIN A, ZHAO M, RYDEL T, GOULD E: Neurogenesis in the adult is involved in the formation of trace memories. Nature (2001) 410(6826):372-376.