Translational Control of Long-Term Synaptic Plasticity and Memory Storage by eIF2α

2006 ◽  
Vol 18 (1-2) ◽  
pp. 187-195 ◽  
Author(s):  
Nahum Sonenberg ◽  
Mauro Costa-Mattioli
Keyword(s):  
Synaptic Plasticity ◽  
Translational Control ◽  
Memory Storage

scholarly journals Multiple components of eIF4F are required for protein synthesis-dependent hippocampal long-term potentiation

2013 ◽  
Vol 109 (1) ◽  
pp. 68-76 ◽  
Author(s):  
Charles A. Hoeffer ◽  
Emanuela Santini ◽  
Tao Ma ◽  
Elizabeth C. Arnold ◽  
Ashley M. Whelan ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Translation Initiation ◽  
Translational Control ◽  
Late Phase ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
General Protein Synthesis ◽  
General Protein

Persistent forms of synaptic plasticity are widely thought to require the synthesis of new proteins. This feature of long-lasting forms of plasticity largely has been demonstrated using inhibitors of general protein synthesis, such as either anisomycin or emetine. However, these drugs, which inhibit elongation, cannot address detailed questions about the regulation of translation initiation, where the majority of translational control occurs. Moreover, general protein synthesis inhibitors cannot distinguish between cap-dependent and cap-independent modes of translation initiation. In the present study, we took advantage of two novel compounds, 4EGI-1 and hippuristanol, each of which targets a different component of the eukaryotic initiation factor (eIF)4F initiation complex, and investigated their effects on long-term potentiation (LTP) at CA3-CA1 synapses in the hippocampus. We found that 4EGI-1 and hippuristanol both attenuated long-lasting late-phase LTP induced by two different stimulation paradigms. We also found that 4EGI-1 and hippuristanol each were capable of blocking the expression of newly synthesized proteins immediately after the induction of late-phase LTP. These new pharmacological tools allow for a more precise dissection of the role played by translational control pathways in synaptic plasticity and demonstrate the importance of multiple aspects of eIF4F in processes underlying hippocampal LTP, laying the foundation for future studies investigating the role of eIF4F in hippocampus-dependent memory processes.

scholarly journals Regulation of memory storage through epigenetic alterations: a new role for RNA

2018 ◽  
Vol 40 (5) ◽  
pp. 12-15
Author(s):  
Alexis Bédécarrats ◽  
David L. Glanzman
Keyword(s):  
Synaptic Plasticity ◽  
Significant Loss ◽  
Memory Storage ◽  
Long Term Memory ◽  
Plasticity Model ◽  
Epigenetic Alterations ◽  
Physical Changes ◽  
Ramón Y Cajal

A fundamental assumption in modern psychology and neuroscience is that memory is stored as physical changes in the brain. More than a century ago, the famous neuroanatomist Ramón Y Cajal (see the article entitled “Santiago Ramón y Cajal, the ultimate scientist?” in this issue of The Biochemist) postulated that changes in the strength of synaptic connections between neurons were the physical substrate for memory. Extensive experimental evidence has since established the dominance of this connectionist view, referred to as the “synaptic plasticity” model. However, although the synaptic plasticity model broadly accords with the results of neurobiological studies of learning and memory, it does not fully account for the extraordinary resilience of memory despite the significant loss of synapses during such phenomena as development, trauma and ageing. Here, we will focus on the newly discovered role of small non-coding RNAs (ncRNAs) as potential master regulators of learning-induced epigenesis, neuronal plasticity and, ultimately, memory. In support of this idea, recent data from our lab indicate that RNA can promote the transfer of long-term memory from a trained to an untrained (naïve) animal.

Differing Mechanisms of Expression for Short- and Long-Term Potentiation

1997 ◽  
Vol 78 (1) ◽  
pp. 321-334 ◽  
Author(s):  
Paul E. Schulz ◽  
Jill C. Fitzgibbons
Keyword(s):  
Synaptic Plasticity ◽  
Extracellular Recording ◽  
Long Term Potentiation ◽  
Memory Storage ◽  
High Frequency Stimulation ◽  
Excitatory Postsynaptic Potential ◽  
Induction Step ◽  
Term Potentiation ◽  
Short And Long Term

Schulz, Paul E. and Jill C. Fitzgibbons. Differing mechanisms of expression for short- and long-term potentiation. J. Neurophysiol. 78: 321–334, 1997. Long-term potentiation (LTP) is a use-dependent form of synaptic plasticity that is of great interest as a cellular mechanism that may contribute to memory storage. It is the sustained phase of population excitatory postsynaptic potential induced by high-frequency stimulation (HFS). HFS can also induce short-term potentiation (STP), a decremental potentiation lasting ∼15 min. It has been unclear whether STP is simply a reversible form of LTP elicited by subthreshold stimuli or whether it is an independently expressed form of synaptic plasticity. We have attempted to clarify the relationship between LTP and STP in the extracellular recording technique in area CA1 of the adult rat hippocampal slice preparation to test four predictions of the hypothesis that LTP and STP are expressed via the same mechanism. First, occluding LTP expression should block STP expression. Saturating LTP under six different conditions, however, did not occlude STP expression. Second, occluding STP expression should occlude LTP expression. The partial or full occlusion of STP by two maneuvers (increasing the stimulus intensity used for HFS or applying 3-isobutyl-1-methylxanthine), however, did not occlude LTP expression. Third, LTP increases and decreases paired-pulse facilitation (PPF), and STP should have the same effect. STP did not change PPF, however. The first three results, then, suggest that STP and LTP are expressed via different mechanisms. Fourth, STP should be maximal near the LTP induction threshold, and then decrease above it. Surprisingly, STP was maximal at or very close to the LTP induction threshold, but it did not decrease above this threshold. This relationship suggests the possibility that STP and LTP share an induction step(s). What is the function of the independently expressed STP? We find that LTP can be induced by two HFSs, each of which is subthreshold for LTP, if the second is given during STP from the first. This suggests that STP can temporarily lower the LTP induction threshold. Three lines of evidence, then, suggest that STP and LTP may be expressed via different mechanisms; however, the proximity of STP saturation to LTP induction suggests that they may share an induction step(s). STP may also have the very important function of temporarily lowering the LTP induction threshold. Finally, these data suggestion caution in interpreting LTP data obtained <20–30 min after HFS, because they may be contaminated by STP, which appears to have different underlying mechanisms.

scholarly journals A Specific Role for Group I mGluRs in Hippocampal LTP and Hippocampus-Dependent Spatial Learning

1999 ◽  
Vol 6 (2) ◽  
pp. 138-152 ◽  
Author(s):  
Detlef Balschun ◽  
Denise Manahan-Vaughan ◽  
Thomas Wagner ◽  
Thomas Behnisch ◽  
Klaus G. Reymann ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Spatial Learning ◽  
Long Term Potentiation ◽  
Specific Role ◽  
Memory Storage ◽  
Group I ◽  
Term Potentiation ◽  
Group I Mglurs ◽  
Freely Moving

Metabotropic glutamate receptors (mGluRs) have been implicated in long-term potentiation and in learning and memory formation. In this study, we tested the effects of group I mGluR inhibition on synaptic plasticity and learning of rats at different levels of organization (1) in the hippocampal slice preparation; (2) in freely moving animals implanted with chronic hippocampal electrodes; and (3) in different spatial learning paradigms. To allow a direct comparison of the effects obtained the same doses were used in all paradigms. Bath-application of the selective group I mGluR antagonist (S)4-carboxyphenylglycine (4-CPG) impaired a decremental long-term potentiation (LTP) induced by a weak tetanization paradigm, but failed to affect a robust LTP generated by strong tetanization. In contrast, 4-CPG impaired a robust LTP in freely moving animals if applied 30 min before tetanization. The same dose of 4-CPG only impeded spatial learning mildly in the eight-arm radial maze and had no effect on a simple configuration of the Y-maze spatial alternation task. In the more difficult configuration of this task, however, 4-CPG caused complete amnesia. The lack of state-dependent 4-CPG actions and the absence of any 4-CPG effects in the open-field test classify the obtained retention deficit as a selective impairment of memory storage. Our results indicate a specific role of group I mGluRs in certain types of synaptic plasticity and of spatial learning.

Variations in Synaptic Plasticity and Types of Memory in Corticohippocampal Networks

1992 ◽  
Vol 4 (3) ◽  
pp. 189-199 ◽  
Author(s):  
Gary Lynch ◽  
Richard Granger
Keyword(s):  
Synaptic Plasticity ◽  
Assembly Line ◽  
Long Term Potentiation ◽  
Memory Storage ◽  
Storage Mechanism ◽  
Behavioral Studies ◽  
Term Potentiation ◽  
Unique Aspect

If Synaptic long-term potentiation (LTP) represents a memory storage mechanism, its induction and expression characteristics may constitute rules governing encoding and read-out of memory in cortical circuitry, The presence of variants of the LTP effect in different anatomical networks provides grounds for predictions about the types of memory operations to which potentiation contributes. Computer modeling studies incorporating the complex rules for LTP induction and the characteristics of expressed potentiation can be used to make such predictions specific. We review ttie types of synaptic plasticity found in the successive stages of the corticohippocampal pathway, and present results indicating that LTP does participate in definably different forms of memory, suggesting a classification of memory types differing somewhat from categories deduced from behavioral studies. Specifically, the results suggest that subtypes of memory operate serially, in an “assembly line” of specialized functions, each of which adds a unique aspect to the processing of memories. The effects of lesions on the encoding versus expression of memory can be interpreted from the perspective of this hypothesis.

Genetic Approaches to the Study of Synaptic Plasticity and Memory Storage

CNS Spectrums ◽  
2003 ◽  
Vol 8 (8) ◽  
pp. 597-610 ◽  
Author(s):  
Ted Abel ◽  
Michael P. Kaplan
Keyword(s):  
Synaptic Plasticity ◽  
Molecular Mechanisms ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Memory Storage ◽  
Long Term Memory ◽  
Protein Signaling ◽  
Term Memory ◽  
Element Binding Protein

ABSTRACTLong-term memory is believed to depend on long-lasting changes in the strength of synaptic transmission known as synaptic plasticity. Understanding the molecular mechanisms of long-term synaptic plasticity is one of the principle goals of neuroscience. Among the most powerful tools being brought to bear on this question are genetically modified mice with changes in the expression or biological activity of genes thought to contribute to these processes. This article reviews how strains of mice with alterations in the cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate-response element-binding protein signaling pathway have advanced our understanding of the biological basis of learning and memory.

scholarly journals Translational Control by MAPK Signaling in Long-Term Synaptic Plasticity and Memory

Cell ◽  
2004 ◽  
Vol 116 (3) ◽  
pp. 467-479 ◽  
Author(s):  
Raymond J Kelleher ◽  
Arvind Govindarajan ◽  
Hae-Yoon Jung ◽  
Hyejin Kang ◽  
Susumu Tonegawa
Keyword(s):  
Synaptic Plasticity ◽  
Translational Control ◽  
Mapk Signaling

Synaptic dysfunction in Parkinson's disease

2010 ◽  
Vol 38 (2) ◽  
pp. 493-497 ◽  
Author(s):  
Vincenza Bagetta ◽  
Veronica Ghiglieri ◽  
Carmelo Sgobio ◽  
Paolo Calabresi ◽  
Barbara Picconi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Plasticity ◽  
Neurodegenerative Disorder ◽  
Long Term Potentiation ◽  
Procedural Memory ◽  
Memory Storage ◽  
Term Potentiation ◽  
Efferent Neurons

In neuronal circuits, memory storage depends on activity-dependent modifications in synaptic efficacy, such as LTD (long-term depression) and LTP (long-term potentiation), the two main forms of synaptic plasticity in the brain. In the nucleus striatum, LTD and LTP represent key cellular substrates for adaptive motor control and procedural memory. It has been suggested that their impairment could account for the onset and progression of motor symptoms of PD (Parkinson's disease), a neurodegenerative disorder characterized by the massive degeneration of dopaminergic neurons projecting to the striatum. In fact, a peculiar aspect of striatal plasticity is the modulation exerted by DA (dopamine) on LTP and LTD. Our understanding of these maladaptive forms of plasticity has mostly come from the electrophysiological, molecular and behavioural analyses of experimental animal models of PD. In PD, a host of cellular and synaptic changes occur in the striatum in response to the massive loss of DA innervation. Chronic L-dopa therapy restores physiological synaptic plasticity and behaviour in treated PD animals, but most of them, similarly to patients, exhibit a reduction in the efficacy of the drug and disabling AIMs (abnormal involuntary movements) defined, as a whole, as L-dopa-induced dyskinesia. In those animals experiencing AIMs, synaptic plasticity is altered and is paralleled by modifications in the postsynaptic compartment. In particular, dysfunctions in trafficking and subunit composition of NMDARs [NMDA (N-methyl-D-aspartate) receptors] on striatal efferent neurons result from chronic non-physiological dopaminergic stimulation and contribute to the pathogenesis of dyskinesias. According to these pathophysiological concepts, therapeutic strategies targeting signalling proteins coupled to NMDARs within striatal spiny neurons could represent new pharmaceutical interventions for PD and L-dopa-induced dyskinesia.

Sign in / Sign up

Export Citation Format

Share Document