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

Viola, Haydeé; Furman, Melina; Izquierdo, Luciana A.; Alonso, Mariana; Barros, Daniela M.; Souza, Márcia María de; Izquierdo, Iván; Medina, Jorge H.

doi:10.1523/jneurosci.20-23-j0002.2000

Cited by 112 publications

(87 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One of us (42) found 11 y ago that exposure to a novel environment can enhance retrieval of IA acquired months before. Novelty enhances the phosphorylation state of CREB in the hippocampus (43) and activates hippocampal MAPKs (44). Salvetti et al (45) showed that novelty presented after weak memory training can promote the memory consolidation of a spatial task.…”

Section: Discussionmentioning

confidence: 99%

Facilitation of fear extinction by novelty depends on dopamine acting on D1-subtype dopamine receptors in hippocampus

Menezes

Alves

Borges

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Extinction is the learned inhibition of retrieval. Recently it was shown that a brief exposure to a novel environment enhances the extinction of contextual fear in rats, an effect explainable by a synaptic tagging-and-capture process. Here we examine whether this also happens with the extinction of another fear-motivated task, inhibitory avoidance (IA), and whether it depends on dopamine acting on D1 or D5 receptors. Rats were trained first in IA and then in extinction of this task. The retention of extinction was measured 24 h later. A 5-min exposure to a novel environment 30 min before extinction training enhanced its retention. Right after exposure to the novelty, animals were given bilateral intrahippocampal infusions of vehicle (VEH), of the protein synthesis inhibitor anisomycin, of the D1/D5 dopaminergic antagonist SCH23390, of the PKA inhibitor Rp-cAMP or of the PKC inhibitor Gö6976, and of the PKA stimulator Sp-cAMP or of the PKC stimulator PMA. The novelty increased hippocampal dopamine levels and facilitated the extinction, which was inhibited by intrahippocampal protein synthesis inhibitor anisomysin, D1/D5 dopaminerdic antagonist SCH23390, or PKA inhibitor Rp-cAMP and unaffected by PKC inhibitor Gö6976; additionally, the hippocampal infusion of PKA stimulator Sp-cAMP reverts the effect of D1/D5 dopaminergic antagonist SCH 23390, but the infusion of PKC stimulator PMA does not. The results attest to the generality of the novelty effect on fear extinction, suggest that it relies on synaptic tagging and capture, and show that it depends on hippocampal dopamine D1 but not D5 receptors.dopamine | inhibitory avoidance | modulation of extinction | novelty | behavioral tagging and capture F rey and Morris (1, 2) described the enhancing influence of neuronal plastic processes [long-term potentiation (LTP) or long-term depression (LTD)] generated at one set of hippocampal synapses on LTP and LTD generated at other synapses. This influence is explainable by interactions between new proteins, called plasticity-related proteins (PRPs), at the two sets of synapses; the PRPs that tag one of them can be captured by those of others and enhance their responsiveness (3-5). Many memories rely on hippocampal LTP and LTD (1, 2, 6-11), and the "synaptic tagging-and-capture" process has been applied to the explanation of interactions between concurrent memories (11-13), among which are novelty and fear acquisition (12,14) and novelty and fear extinction (15, 16). Exposure to novelty [an open field (OF) in which they had never been before] involves two consecutive processes: its detection, which is very brief (seconds), and the immediately ensuing habituation (17), which lasts much longer; both rely on hippocampal LTD (18). With a relatively restricted time window before and/or after an extinction trial, novelty can enhance the extinction of contextual fear conditioning (CFC) lastingly (15,16). This is obviously of potential importance for exposure therapy (18-21).In rodents, the exploration of a novel environment, object, ...

show abstract

Section: Discussionmentioning

confidence: 99%

Facilitation of fear extinction by novelty depends on dopamine acting on D1-subtype dopamine receptors in hippocampus

Menezes

Alves

Borges

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…This phosphorylation is an essential step in the activation of CREB-mediated transcription (Gonzalez and Montminy, 1989;Ginty et al, 1994;Bito et al, 1996;Silva et al, 1998). Therefore, phosphorylation of CREB at serine 133 has been used to identify brain regions activated in gene expression-dependent memory processes (Viola et al, 2000;Hall et al, 200l).…”

Section: Creb Activation In Distinct Brain Regions In Reconsolidationmentioning

confidence: 99%

Brain Region-Specific Gene Expression Activation Required for Reconsolidation and Extinction of Contextual Fear Memory

Mamiya¹,

Fukushima²,

Suzuki³

et al. 2009

J. Neurosci.

248

245

View full text Add to dashboard Cite

During fear conditioning, animals learn an association between a previously neutral or conditioned stimulus (CS) and an aversive or unconditioned stimulus (US). Subsequent reexposure to the CS alone triggers two competing processes. Brief reexposure to the CS initiates reconsolidation processes that serve to stabilize or maintain the original CS-US memory. In contrast, more prolonged reexposure to the CS leads to the formation of an inhibitory extinction (CS-no US) memory. Previous studies have established that both reconsolidation and extinction require gene expression. Consistent with this, here we first show that genetic disruption of cAMPresponsive element-binding protein (CREB)-mediated transcription blocks both reconsolidation and long-term extinction of contextual fear memory. We next asked whether reconsolidation and extinction engage CREB-mediated transcription in distinct brain regions. Accordingly, we used immunohistochemical approaches to characterize the activation of the transcription factor CREB [as well as the expression of the CREB-dependent gene Arc (activity-regulated cytoskeleton-associated protein)] after brief versus prolonged reexposure to a previously conditioned context. After brief reexposure, we observed significant activation of CREB-mediated gene expression in the hippocampus and amygdala. In contrast, after the prolonged reexposure, we observed significant activation of CREB-mediated gene expression in the amygdala and prefrontal cortex. Finally, we showed that blocking protein synthesis in either the hippocampus or the amygdala blocked reconsolidation of contextual fear memory, whereas similar blockade in the amygdala and prefrontal cortex prevented the formation of extinction memory. These experiments establish that reactivated contextual fear memories undergo CREB-dependent reconsolidation or extinction in distinct brain regions.

show abstract

“…CREB phosphorylation is known to increase during neural activity and to lead to long-lasting synaptic plasticity, especially in hippocampus-dependent memory (Mayford and Kandel, 1999;Viola et al, 2000;Colombo et al, 2003). Moreover, antisense oligodeoxynucleotide-mediated disruption of the CREB gene in the hippocampus was found to impair long-term memory formation (Guzowski and McGaugh, 1997), and a targeted mutation of the CREBh-isoform was associated with abnormal learning and memory (Bourtchuladze et al, 1994;Blendy et al, 1996), whereas increasing the level of CREB in the brain enhanced the formation of long-term memory (Josselyn et al, 2001).…”

Section: Neuropathological Features Of Tg-bctf99/b6 As An Ad Modelmentioning

confidence: 99%

Progressive neuronal loss and behavioral impairments of transgenic C57BL/6 inbred mice expressing the carboxy terminus of amyloid precursor protein

Lee

Song

et al. 2006

Neurobiology of Disease

View full text Add to dashboard Cite

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

Cited by 112 publications

References 29 publications

Facilitation of fear extinction by novelty depends on dopamine acting on D1-subtype dopamine receptors in hippocampus

Facilitation of fear extinction by novelty depends on dopamine acting on D1-subtype dopamine receptors in hippocampus

Brain Region-Specific Gene Expression Activation Required for Reconsolidation and Extinction of Contextual Fear Memory

Progressive neuronal loss and behavioral impairments of transgenic C57BL/6 inbred mice expressing the carboxy terminus of amyloid precursor protein

Contact Info

Product

Resources

About