Long-term memory for place learning is facilitated by expression of cAMP response element-binding protein in the dorsal hippocampus

Brightwell, Jennifer J.; Smith, Clayton A.; Neve, Rachael L.; Colombo, Paul J.

doi:10.1101/lm.395407

Cited by 84 publications

(54 citation statements)

References 39 publications

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“…This result resembles those reported after manipulation of the hippocampal complex. Indeed, antisensemediated down-regulation of CREB expression within the hippocampus immediately after training has been shown to block spatial memory (10), whereas viral-mediated overexpression of CREB facilitated retention without affecting the acquisition of spatial information (23).…”

Section: Discussionmentioning

confidence: 99%

Ventral striatal plasticity and spatial memory

Ferretti

Roullet

Sargolini

et al. 2010

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

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Spatial memory formation is a dynamic process requiring a series of cellular and molecular steps, such as gene expression and protein translation, leading to morphological changes that have been envisaged as the structural bases for the engram. Despite the role suggested for medial temporal lobe plasticity in spatial memory, recent behavioral observations implicate specific components of the striatal complex in spatial information processing. However, the potential occurrence of neural plasticity within this structure after spatial learning has never been investigated. In this study we demonstrate that blockade of cAMP response element binding protein-induced transcription or inhibition of protein synthesis or extracellular proteolytic activity in the ventral striatum impairs longterm spatial memory. These findings demonstrate that, in the ventral striatum, similarly to what happens in the hippocampus, several key molecular events crucial for the expression of neural plasticity are required in the early stages of spatial memory formation. T he formation of long-term memories is believed to involve a dynamic process by which a labile memory is progressively converted into a more stable and potentially permanent trace. Evidence for such a time-dependent process comes from studies demonstrating that electroconvulsive shock produces amnesia only if delivered shortly after learning, whereas the same treatment is ineffective when delivered several hours later (1). Long-term memory is accompanied by changes in neuronal morphology and connectivity, and these alterations are thought to be essential for the stabile encoding of new information (2). This transformation has been suggested to depend upon plastic changes that involve a sequence of specific and coordinated cellular processes. These begin with neurotransmitter receptor activation that induces shortterm changes in synaptic efficacy based on receptor phosphorylation and trafficking (3, 4). Subsequently, alterations in gene expression and protein synthesis occur that are the basis for longterm structural modifications (5, 6).A key issue in the study of memory in vertebrates is the brain site at which these processes occur. Clinical evidence in humans suggests that structures within the medial temporal lobe (MTL) play a prominent role in long-term memories. MTL lesions induce profound deficits in the formation of long-lasting declarative memories while sparing the acquisition of nondeclarative memories such as visual-motor skills (7,8). Such findings suggest that the hippocampus might be an essential site where plasticity occurs in the initial steps of declarative memory stabilization. Accordingly, those molecular events thought to be crucial for the long-term encoding of memories such as regulation of gene expression and protein synthesis, as well as structural changes, have been described in the hippocampus after spatial learning (6, 9, 10).Recent experimental evidence, however, demonstrates that structures different from the hippocampus might also be involved in ...

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Section: Discussionmentioning

confidence: 99%

Ventral striatal plasticity and spatial memory

Ferretti

Roullet

Sargolini

et al. 2010

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

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“…However, little is known about the impacts of increased levels of CREB activity on memory performance. Indeed, recent studies using viruses to overexpress CREB suggested that the upregulation of CREB activity improves memory formation (Josselyn et al, 2001;Brightwell et al, 2007;Han et al, 2008;Zhou et al, 2009). In contrast, the memory performance of transgenic mice expressing a dominant active CREB mutant (VP16-CREB) in the forebrain displayed contradictory results (i.e., the impairment and weak improvement of memory performance) (Viosca et al, 2009a,b).…”

Section: Introductionmentioning

confidence: 99%

Upregulation of CREB-Mediated Transcription Enhances Both Short- and Long-Term Memory

Suzuki¹,

Fukushima²,

Mukawa³

et al. 2011

Journal of Neuroscience

228

206

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Unraveling the mechanisms by which the molecular manipulation of genes of interest enhances cognitive function is important to establish genetic therapies for cognitive disorders. Although CREB is thought to positively regulate formation of long-term memory (LTM), gain-of-function effects of CREB remain poorly understood, especially at the behavioral level. To address this, we generated four lines of transgenic mice expressing dominant active CREB mutants (CREB-Y134F or CREB-DIEDML) in the forebrain that exhibited moderate upregulation of CREB activity. These transgenic lines improved not only LTM but also long-lasting long-term potentiation in the CA1 area in the hippocampus. However, we also observed enhanced short-term memory (STM) in contextual fear-conditioning and social recognition tasks. Enhanced LTM and STM could be dissociated behaviorally in these four lines of transgenic mice, suggesting that the underlying mechanism for enhanced STM and LTM are distinct. LTM enhancement seems to be attributable to the improvement of memory consolidation by the upregulation of CREB transcriptional activity, whereas higher basal levels of BDNF, a CREB target gene, predicted enhanced shorter-term memory. The importance of BDNF in STM was verified by microinfusing BDNF or BDNF inhibitors into the hippocampus of wild-type or transgenic mice. Additionally, increasing BDNF further enhanced LTM in one of the lines of transgenic mice that displayed a normal BDNF level but enhanced LTM, suggesting that upregulation of BDNF and CREB activity cooperatively enhances LTM formation. Our findings suggest that CREB positively regulates memory consolidation and affects memory performance by regulating BDNF expression.

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“…In particular, the mammalian target of rapamycin, an Akt pathway target, plays a central role in translational control and has been shown to be critical for long-lasting plasticity (120)(121)(122) . Most importantly, extensive evidence derived from experimental systems ranging from molluscs to human subjects indicates that the cAMP response element binding protein (CREB) is a core component of the molecular switch that converts short-to long-term memory (123)(124)(125) . In mammals, CREB has been shown to regulate the expression of several genes during learning and memory, particularly gene products that are needed to stabilise the synaptic changes that are triggered during learning (117,126,127) (Fig.…”

Section: Molecular Basis Of Memorymentioning

confidence: 99%

Flavonoids as modulators of memory and learning: molecular interactions resulting in behavioural effects

Rendeiro

Guerreiro

et al. 2012

Proc. Nutr. Soc.

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There is considerable interest in the potential of a group of dietary-derived phytochemicals known as flavonoids in modulating neuronal function and thereby influencing memory, learning and cognitive function. The present review begins by detailing the molecular events that underlie the acquisition and consolidation of new memories in the brain in order to provide a critical background to understanding the impact of flavonoid-rich diets or pure flavonoids on memory. Data suggests that despite limited brain bioavailability, dietary supplementation with flavonoid-rich foods, such as blueberry, green tea and Ginkgo biloba lead to significant reversals of age-related deficits on spatial memory and learning. Furthermore, animal and cellular studies suggest that the mechanisms underpinning their ability to induce improvements in memory are linked to the potential of absorbed flavonoids and their metabolites to interact with and modulate critical signalling pathways, transcription factors and gene and/or protein expression which control memory and learning processes in the hippocampus; the brain structure where spatial learning occurs. Overall, current evidence suggests that human translation of these animal investigations are warranted, as are further studies, to better understand the precise cause-and-effect relationship between flavonoid intake and cognitive outputs. Flavonoids: Memory: Learning: HippocampusDiet is an important lifestyle factor, which in recent times has been investigated for its influence on cognitive function and the incidence and onset of neurodegenerative disorders (1,2) . It has long been known that a diet high in saturated fats negatively impacts on cognitive processing and increases the risk of neurological dysfunction in both animals and human subjects (3,4) , while energy restriction (reduction in approximately 30 % energy intake) protects the brain from injury (5,6) . Recently, significant evidence has emerged to indicate that phytochemical-rich foods, and in particular those rich in flavonoids, may reverse agerelated deficits in cognitive function in both animals and human subjects (7)(8)(9) . For example, the PAQUID prospective study examined cognitive performance in 1640 subjects (aged at least 65 years and cognitively normal at baseline) on four occasions over a 10-year-period and found that flavonoid-intake was associated with a significantly better cognitive performance over time (7) (P = 0 . 046). Furthermore, a cross-sectional study examining the relationship between the intake of three common flavonoid-containing foods (chocolate, wine and tea) and cognitive performance in elderly individuals revealed that there was a dose-dependent, positive relationship between the intake of these foods and performance on multiple cognitive outcomes (Kendrick Object Learning Test, Digit Symbol Test, Block Design, Mini-Mental State Examination and Controlled Oral Word Association Test) (10) . More recently, the consumption of dietary flavonoids, especially

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Long-term memory for place learning is facilitated by expression of cAMP response element-binding protein in the dorsal hippocampus

Cited by 84 publications

References 39 publications

Ventral striatal plasticity and spatial memory

Ventral striatal plasticity and spatial memory

Upregulation of CREB-Mediated Transcription Enhances Both Short- and Long-Term Memory

Flavonoids as modulators of memory and learning: molecular interactions resulting in behavioural effects

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