Storage of Spatial Information by the Maintenance Mechanism of LTP

Pastalkova, Eva; Serrano, Peter A.; Pinkhasova, Deana; Wallace, Emma Jane Claire; Fenton, André A.; Sacktor, Todd Charlton

doi:10.1126/science.1128657

Cited by 769 publications

(789 citation statements)

References 25 publications

(38 reference statements)

Supporting

Mentioning

735

Contrasting

Unclassified

Order By: Relevance

“…The effect of the PKC inhibitor was not restricted to one mouse strain, but was also profound in C57BL/6NCrl mice that typically acquire and generalize strong fear responses (Radulovic et al, 1998b) and exhibit resistance to contextual fear extinction (Stiedl et al, 1999;Siegmund et al, 2005). Together with data showing effects of long-term activation of atypical hippocampal PKC on behavioral performance (Pastalkova et al, 2006), our data suggest that typical PKCs might also contribute to persistent fear-motivated behavior.…”

Section: Discussionsupporting

confidence: 50%

Regulatory Mechanisms of Fear Extinction and Depression-Like Behavior

Tronson

Schrick

Fischer

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

Human anxiety is frequently accompanied by depression, and when they co-occur both conditions exhibit greater severity and resistance to treatment. Little is known, however, about the molecular processes linking these emotional and mood disorders. Based on previously reported phosphorylation patterns of extracellular signal-regulated kinase (ERK) in the brain, we hypothesized that ERK's upstream activators intertwine fear and mood regulation through their hippocampal actions. We tested this hypothesis by studying the upstream regulation of ERK signaling in behavioral models of fear and depression. Wild-type and ERK1-deficient mice were used to study the dorsohippocampal actions of the putative ERK activators: mitogen-activated and extracellular signal-regulated kinase (MEK), protein kinase C (PKC), and cAMP-dependent protein kinase (PKA). Mice lacking ERK1 exhibited enhanced fear extinction and reduced depression caused by overactivation of ERK2. Both behaviors were reversed by inhibition of MEK, however the extinction phenotype depended on hippocampal, whereas the depression phenotype predominantly involved extrahippocampal MEK. Unexpectedly, inhibition of PKC accelerated extinction and decreased depression by ERK-independent mechanisms, whereas inhibition of PKA did not produce detectable molecular or behavioral effects in the employed paradigm. These results indicate that, contrary to fear conditioning but similar to mood stabilization, extinction of fear required upregulation of MEK/ERK and downregulation of ERK-independent PKC signaling. The dissociation of these pathways may thus represent a common mechanism for fear and mood regulation, and a potential therapeutic option for comorbid anxiety and depression.

show abstract

Section: Discussionsupporting

confidence: 50%

Regulatory Mechanisms of Fear Extinction and Depression-Like Behavior

Tronson

Schrick

Fischer

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…It is an atypical PKC enzyme with the ability to be autonomously active once synthesized, thereby stabilizing lasting changes required for sustained LTP. [96][97][98][99] However more recent studies show that PKMz, is dispensable for LTP associated with memory. [100][101][102] In 1998, Tompa and Friedrich put forth the prion theory of memory wherein they suggested that propagation of a non-toxic conformational state of prions could underlie cellular functions like memory storage.…”

Section: Biochemical Models For Ltm Maintenancementioning

confidence: 99%

Long-term memory consolidation: The role of RNA-binding proteins with prion-like domains

Sudhakaran

Ramaswami

2016

RNA Biology

View full text Add to dashboard Cite

Long-term and short-term memories differ primarily in the duration of their retention. At a molecular level, long-term memory (LTM) is distinguished from short-term memory (STM) by its requirement for new gene expression. In addition to transcription (nuclear gene expression) the translation of stored mRNAs is necessary for LTM formation. The mechanisms and functions for temporal and spatial regulation of mRNAs required for LTM is a major contemporary problem, of interest from molecular, cell biological, neurobiological and clinical perspectives. This review discusses primary evidence in support for translational regulatory events involved in LTM and a model in which different phases of translation underlie distinct phases of consolidation of memories. However, it focuses largely on mechanisms of memory persistence and the role of prion-like domains in this defining aspect of long-term memory. We consider primary evidence for the concept that Cytoplasmic Polyadenylation Element Binding (CPEB) protein enables the persistence of formed memories by transforming in prion-like manner from a soluble monomeric state to a self-perpetuating and persistent polymeric translationally active state required for maintaining persistent synaptic plasticity. We further discuss prion-like domains prevalent on several other RNA-binding proteins involved in neuronal translational control underlying LTM. Growing evidence indicates that such RNA regulatory proteins are components of mRNP (RiboNucleoProtein) granules. In these proteins, prion-like domains, being intrinsically disordered, could mediate weak transient interactions that allow the assembly of RNP granules, a source of silenced mRNAs whose translation is necessary for LTM. We consider the structural bases for RNA granules formation as well as functions of disordered domains and discuss how these complicate the interpretation of existing experimental data relevant to general mechanisms by which prion-domain containing RBPs function in synapse specific plasticity underlying LTM.

show abstract

“…Pharmacological experiments indicate that the atypical protein kinase C known as protein kinase Mζ (PKM-ζ) may be necessary and sufficient for the maintenance of L-LTP in the hippocampus (Ling et al, 2002;Pastalkova et al, 2006) and can also be involved in synaptic tagging . More recently, it has been proposed that CaMKII could also participate in setting synaptic tags for L-LTP capture, whereas MAPKs would play an equivalent role for L-LTD (Sajikumar et al, 2007a).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Synapse-specific stabilization of plasticity processes: The synaptic tagging and capture hypothesis revisited 10 years later

Barco

Armentia

Alarcón

2008

Neuroscience & Biobehavioral Reviews

View full text Add to dashboard Cite

Synapse-specific stabilization of plasticity processes: The synaptic tagging and capture hypothesis revisited ten years later, Neuroscience and Biobehavioral Reviews (2008Reviews ( ), doi:10.1016Reviews ( /j.neubiorev.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A c c e p t e d m a n u s c r i p t A c c e p t e d m a n u s c r i p tThe STC hypothesis revisited 2 Abstract A decade ago, the synaptic tagging hypothesis was proposed to explain how newly synthesized plasticity products can be specifically targeted to active synapses. A growing number of studies have validated the seminal findings that gave rise to this model, as well as contributed to unveil and expand the range of mechanisms underlying late-associativity and neuronal computation.Here, we will review what it was learnt during this past decade regarding the cellular and molecular mechanisms underlying synaptic tagging and synaptic capture. The accumulated experimental evidence has widened the theoretical framework set by the synaptic tagging and capture (STC) model and introduced concepts that were originally considered part of alternative models for explaining synapse-specific LTP. As a result, we believe that the STC model, now improved and expanded with these new ideas and concepts, still represents the most compelling hypothesis to explain late-associativity in synapse-specific plasticity processes. We will also discuss the impact of this model in our view of the integrative capability of neurons and associative learning. wordsKeywords: synaptic plasticity; LTP; associative learning; neuronal computation; synaptic tagging; synaptic capture; metaplasticity A c c e p t e d m a n u s c r i p tThe STC hypothesis revisited 3 Contents

show abstract

Storage of Spatial Information by the Maintenance Mechanism of LTP

Cited by 769 publications

References 25 publications

Regulatory Mechanisms of Fear Extinction and Depression-Like Behavior

Regulatory Mechanisms of Fear Extinction and Depression-Like Behavior

Long-term memory consolidation: The role of RNA-binding proteins with prion-like domains

Synapse-specific stabilization of plasticity processes: The synaptic tagging and capture hypothesis revisited 10 years later

Contact Info

Product

Resources

About