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

• Published in: The Journal of neuroscience Vol. 20; no. 23; pp. 112 - RC112
• Main Authors: Viola, Haydee, Furman, Melina, Izquierdo, Luciana A. I, Alonso, Mariana, Barros, Daniela M, de Souza, Marcia M, Izquierdo, Ivan, Medina, Jorge H
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01-12-2000; Society for Neuroscience
• Subjects: Amnesia, Retrograde - drug therapy; Amnesia, Retrograde - metabolism; Animals; Avoidance Learning - drug effects; Avoidance Learning - physiology; Behavior, Animal - drug effects; Behavior, Animal - physiology; Biomarkers; Cyclic AMP - administration & dosage; Cyclic AMP - analogs & derivatives; Cyclic AMP Response Element-Binding Protein - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; Exploratory Behavior - drug effects; Exploratory Behavior - physiology; Hippocampus - chemistry; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - physiology; Infusions, Parenteral; Male; Memory - drug effects; Memory - physiology; Microinjections; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases - metabolism; Phosphorylation - drug effects; Rapid Communication; Rats; Rats, Wistar; Retention (Psychology) - drug effects; Retention (Psychology) - physiology; Thionucleotides - administration & dosage; Time
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.20-23-j0002.2000

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.