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The Journal of Neuroscience, 0000, 20:RC112:1-5

RAPID COMMUNICATION
Phosphorylated cAMP Response Element-Binding Protein as a Molecular Marker of Memory Processing in Rat Hippocampus: Effect of Novelty

Haydée Viola¹, Melina Furman¹, Luciana A. I. Izquierdo², Mariana Alonso¹, Daniela M. Barros², Marcia M. de Souza², Iván Izquierdo², and Jorge H. Medina¹

¹ Instituto de Biologia Celular y Neurociencias, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 3, 1121 Buenos Aires, Argentina, and ² Centro de Memoria, Departamento de Bioquimica, Instituto de Biociencias, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

From mollusks to mammals the activation of cAMP response element-binding protein (CREB) appears to be an important step in the formation of long-term memory (LTM). Here we show that a 5 min exposure to a novel environment (open field) 1 hr after acquisition of a one-trial inhibitory avoidance training hinders both the formation of LTM for the avoidance task and the increase in the phosphorylation state of hippocampal Ser 133 CREB [phosphorylated CREB (pCREB)] associated with the avoidance training. To determine whether this LTM deficit is attributable to the reduced pCREB level, rats were bilaterally cannulated to deliver Sp-adenosine 3',5'-cyclic monophosphothioate (Sp-cAMPS), an activator of PKA. Infusion of Sp-Adenosine 3',5'-cyclic monophosphothioate Sp-cAMPS to CA1 region increased hippocampal pCREB levels and restored normal LTM of avoidance learning in rats exposed to novelty. Moreover, a 5 min exposure to the open field 10 min before the avoidance training interferes with the amnesic effect of a second 5 min exposure to the open field 1 hr after avoidance training and restores the hippocampal levels of pCREB. In contrast, the avoidance training-associated activation of extracellular signal-regulated kinases (p42 and p44 mitogen-activated protein kinases) in the hippocampus is not altered by novelty. Together, these findings suggest that novelty regulates LTM formation by modulating the phosphorylation state of CREB in the hippocampus.

Key words: phosphorylated CREB; hippocampus; avoidance training; memory processing; novelty; amnesia

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Copyright © 0000 Society for Neuroscience  0270-6474/00/$05.00/0

This article has been cited by other articles:

				I. Izquierdo, L. R. Bevilaqua, J. I. Rossato, R. H. Lima, J. H. Medina, and M. Cammarota Age-dependent and age-independent human memory persistence is enhanced by delayed posttraining methylphenidate administration PNAS, December 9, 2008; 105(49): 19504 - 19507. [Abstract] [Full Text] [PDF]

				W. C. Abraham, B. Logan, J. M. Greenwood, and M. Dragunow Induction and Experience-Dependent Consolidation of Stable Long-Term Potentiation Lasting Months in the Hippocampus J. Neurosci., November 1, 2002; 22(21): 9626 - 9634. [Abstract] [Full Text] [PDF]

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