Spatial memory in the Morris water maze and activation of cyclic AMP response element-binding (CREB) protein within the mouse hippocampus

Porte, Yves; Buhot, Marie-Christine; Mons, Nicole

doi:10.1101/lm.1094208

Cited by 62 publications

(47 citation statements)

References 67 publications

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“…In agreement with our previous observations (Porte et al, 2008b), spatial reference training evoked a biphasic increase in pCREB at 15 min and 8 h post-training time points (vs. 60 min: Ps < 0.01; Fig. 4A for Day 9).…”

Section: Immunohistochemical and Western Blots Analysessupporting

confidence: 91%

“…Memory formation and persistence require multiple waves of transcription and translation (Igaz et al, 2002;Dudai and Eisenberg, 2004;Bekinschtein et al, 2007Bekinschtein et al, , 2008; Slipczuk et al, 2009;Katche et al, 2010). In accordance with this, we and others have previously demonstrated that consolidation of hippocampal-dependent, contextual and spatial, LTM formation relies on at least two waves of CREB activation, one just after learning and the other between 3 and 9 h posttraining (Bernabeu et al, 1997;Cammarota et al, 2000;Stanciu et al, 2001;Trifilieff et al, 2006;Martel et al, 2007;Porte et al, 2008b). Furthermore, we also found that alteration of the early CREB phosphorylation in CA1 correlates with spatial memory impairments during normal aging (Porte et al, 2008a).…”

Section: Introductionsupporting

confidence: 57%

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Extinction of spatial memory alters CREB phosphorylation in hippocampal CA1

et al. 2010

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Although the importance of cAMP-response element binding protein (CREB) phosphorylation in long-term memory formation is well documented for hippocampus-dependent tasks, little is known about the changes in phosphorylated CREB (pCREB) that occur during the process of extinction. The purpose of this study was to characterize the temporal patterns of pCREB in the CA1 and the amygdala after the extinction of previously acquired spatial information in the water maze. Mice were trained to find a hidden platform located at a fixed position and then were given extinction sessions in which the platform was either absent (NoPF) or relocated every day (RandomPF). We show that water maze spatial training evoked a biphasic response of pCREB in the CA1, with two different peaks occurring 15 min and 8 h postacquisition. The extinction of the original spatial preference significantly reduced the two peaks of CA1 pCREB in both RandomPF and NoPF groups whereas CA1 pCREB at 60 min post-training remained unaffected. Moreover, the early and late phases of extinction training produced regionally dissociable effects on pCREB in the CA1 and the lateral nucleus of the amygdala. These findings provide new insights on the molecular dynamics and anatomical dissociations underlying spatial memory and extinction learning.

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Section: Immunohistochemical and Western Blots Analysessupporting

confidence: 91%

Section: Introductionsupporting

confidence: 57%

Extinction of spatial memory alters CREB phosphorylation in hippocampal CA1

et al. 2010

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“…Collectively, these data position miR-212/132 among a number of other CREB-regulated genes that are required for learning and memory formation (Hall et al 2001;Colombo et al 2003). Indeed, CREB-dependent transcription is induced following an array of learning paradigms and is required for normal cognitive function (Impey et al 1998;Mizuno et al 2002;Porte et al 2008). Nevertheless, while moderate increases in CREB activity facilitate learning, chronic enhancement of CREB-dependent transcription impairs cognitive capacity, paralleling the learning phenotypes observed in tTA::miR-132 animals (Viosca et al 2009;Hansen et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome

et al. 2016

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miR-132 and miR-212 are structurally related microRNAs that have been found to exert powerful modulatory effects within the central nervous system (CNS). Notably, these microRNAs are tandomly processed from the same noncoding transcript, and share a common seed sequence: thus it has been difficult to assess the distinct contribution of each microRNA to gene expression within the CNS. Here, we employed a combination of conditional knockout and transgenic mouse models to examine the contribution of the miR-132/-212 gene locus to learning and memory, and then to assess the distinct effects that each microRNA has on hippocampal gene expression. Using a conditional deletion approach, we show that miR-132/-212 double-knockout mice exhibit significant cognitive deficits in spatial memory, recognition memory, and in tests of novel object recognition. Next, we utilized transgenic miR-132 and miR-212 overexpression mouse lines and the miR-132/-212 double-knockout line to explore the distinct effects of these two miRNAs on the transcriptional profile of the hippocampus. Illumina sequencing revealed that miR-132/-212 deletion increased the expression of 1138 genes; Venn analysis showed that 96 of these genes were also downregulated in mice overexpressing miR-132. Of the 58 genes that were decreased in animals overexpressing miR-212, only four of them were also increased in the knockout line. Functional gene ontology analysis of downregulated genes revealed significant enrichment of genes related to synaptic transmission, neuronal proliferation, and morphogenesis, processes known for their roles in learning, and memory formation. These data, coupled with previous studies, firmly establish a role for the miR-132/-212 gene locus as a key regulator of cognitive capacity. Further, although miR-132 and miR-212 share a seed sequence, these data indicate that these miRNAs do not exhibit strongly overlapping mRNA targeting profiles, thus indicating that these two genes may function in a complex, nonredundant manner to shape the transcriptional profile of the CNS. The dysregulation of miR-132/-212 expression could contribute to signaling mechanisms that are involved in an array of cognitive disorders.

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“…After completion of the last training session, the brains of mice were removed to assess learning-induced brain regional expression of pCREB (Martel et al, 2006;Porte et al, 2008) and c-Fos (Colombo et al, 2003). Under anesthesia, animals were perfused transcardially with an ice-cold solution of 4% paraformaldehyde in phosphate buffer (0.1 M) pH 7.4.…”

Section: Immunochemistrymentioning

confidence: 99%

Disrupting Effect of Drug-Induced Reward on Spatial But Not Cue-Guided Learning: Implication of the Striatal Protein Kinase A/cAMP Response Element-Binding Protein Pathway

Baudonnat¹,

Guillou²,

Husson³

et al. 2011

J. Neurosci.

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The multiple memory systems hypothesis posits that different neural circuits function in parallel and may compete for information processing and storage. For example, instrumental conditioning would depend on the striatum, whereas spatial memory may be mediated by a circuit centered on the hippocampus. However, the nature of the task itself is not sufficient to select durably one system over the other. In this study, we investigated the effects of natural and pharmacological rewards on the selection of a particular memory system during learning. We compared the effects of food-or drug-induced activation of the reward system on cue-guided versus spatial learning using a Y-maze discrimination task. Drug-induced reward severely impaired the acquisition of a spatial discrimination task but spared the cued version of the task. Immunohistochemical analysis of the phosphorylated form of the cAMP response element binding (CREB) protein and c-Fos expression induced by behavioral testing revealed that the spatial deficit was associated with a decrease of both markers within the hippocampus and the prefrontal cortex. In contrast, drug reward potentiated the cued learning-induced CREB phosphorylation within the dorsal striatum. Administration of the protein kinase A inhibitor 8-Bromo-adenosine-3',5'-cyclic monophosphorothioate Rp isomer (Rp-cAMPS) into the dorsal striatum before training completely reversed the drug-induced spatial deficit and restored CREB phosphorylation levels within the hippocampus and the prefrontal cortex. Therefore, drug-induced striatal hyperactivity may underlie the declarative memory deficit reported here. This mechanism could represent an important early step toward the development of addictive behaviors by promoting conditioning to the detriment of more flexible forms of memory.

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Spatial memory in the Morris water maze and activation of cyclic AMP response element-binding (CREB) protein within the mouse hippocampus

Cited by 62 publications

References 67 publications

Extinction of spatial memory alters CREB phosphorylation in hippocampal CA1

Extinction of spatial memory alters CREB phosphorylation in hippocampal CA1

Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome

Disrupting Effect of Drug-Induced Reward on Spatial But Not Cue-Guided Learning: Implication of the Striatal Protein Kinase A/cAMP Response Element-Binding Protein Pathway

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