Differential requirement of de novo Arc protein synthesis in the insular cortex and the amygdala for safe and aversive taste long-term memory formation

2018 ◽  
Vol 342 ◽  
pp. 89-93 ◽  
Author(s):  
Kioko Guzmán-Ramos ◽  
Archana Venkataraman ◽  
Jean-Pascal Morin ◽  
Daniel Osorio-Gómez ◽  
Federico Bermúdez-Rattoni
Keyword(s):  
Protein Synthesis ◽  
De Novo ◽  
Insular Cortex ◽  
Memory Formation ◽  
Long Term Memory ◽  
Term Memory ◽  
Aversive Taste

The Integrated Stress Response in Memory and Cognitive Disorders

2020 ◽  
Author(s):  
Jacqunae L. Mays ◽  
Mauro Costa-Mattioli
Keyword(s):  
Protein Synthesis ◽  
Stress Response ◽  
Cognitive Disorders ◽  
Memory Formation ◽  
Model Systems ◽  
Long Term Memory ◽  
Integrated Stress Response ◽  
Term Memory ◽  
Wide Range

The integrated stress response (ISR) is an evolutionarily conserved intracellular signaling network that responds to proteostasis defects and stress conditions by tuning protein synthesis rates. While it has been long recognized that long-term memory formation requires new protein synthesis, our understanding of the central translational control mechanisms that regulate memory formation has advanced vastly. Indeed, novel causal and convergent evidence across different species and model systems shows that the ISR serves as a universal regulator of long-term memory formation. This chapter discusses the evidence explaining how inhibition of the ISR enhances long-term memory formation while activation of the ISR prevents it. In addition, it highlights the role of the ISR in different forms of long-lasting synaptic plasticity in the brain. Finally, the chapter addresses how dysregulated ISR signaling contributes to the pathogenesis of a wide range of cognitive and neurodegenerative disorders and discusses the future prospects for therapeutically targeting the ISR for the treatment of cognitive disorders.

scholarly journals New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Roi Levy ◽  
David Levitan ◽  
Abraham J Susswein
Keyword(s):  
Protein Synthesis ◽  
Memory Formation ◽  
Long Term Memory ◽  
Learning Paradigm ◽  
Translation Memory ◽  
Sleep Phase ◽  
Term Memory ◽  
New Learning ◽  
Effective Training

Brief experiences while a memory is consolidated may capture the consolidation, perhaps producing a maladaptive memory, or may interrupt the consolidation. Since consolidation occurs during sleep, even fleeting experiences when animals are awakened may produce maladaptive long-term memory, or may interrupt consolidation. In a learning paradigm affecting Aplysia feeding, when animals were trained after being awakened from sleep, interactions between new experiences and consolidation were prevented by blocking long-term memory arising from the new experiences. Inhibiting protein synthesis eliminated the block and allowed even a brief, generally ineffective training to produce long-term memory. Memory formation depended on consolidative proteins already expressed before training. After effective training, long term memory required subsequent transcription and translation. Memory formation during the sleep phase was correlated with increased CREB1 transcription, but not CREB2 transcription. Increased C/EBP transcription was a correlate of both effective and ineffective training and of treatments not producing memory.

scholarly journals Chemogenetic evidence that rapid neuronal de novo protein synthesis is required for consolidation of long-term memory

2019 ◽  
Author(s):  
Prerana Shrestha ◽  
Pinar Ayata ◽  
Pedro Herrero-Vidal ◽  
Francesco Longo ◽  
Alexandra Gastone ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Translational Control ◽  
De Novo ◽  
Kinase Domain ◽  
Stimulus Generalization ◽  
Long Term Memory ◽  
Term Memory ◽  
The Cost

AbstractTranslational control of memory processes is a tightly regulated process where the coordinated interaction and modulation of translation factors provides a permissive environment for protein synthesis during memory formation. Existing methods used to block translation lack the spatiotemporal precision to investigate cell-specific contributions to consolidation of long-term memories. Here, we have developed a novel chemogenetic mouse resource for cell type-specific and drug-inducible protein synthesis inhibition (ciPSI) that utilizes an engineered version of the catalytic kinase domain of dsRNA-activated protein (PKR). ciPSI allows rapid and reversible phosphorylation of eIF2α causing a block on general translation by 50% in vivo. Using this resource, we discovered that temporally structured pan-neuronal protein synthesis is required for consolidation of long-term auditory threat memory. Targeted protein synthesis inhibition in CamK2α expressing glutamatergic neurons in lateral amygdala (LA) impaired long-term memory, which was recovered with artificial chemogenetic reactivation at the cost of stimulus generalization. Conversely, genetically reducing phosphorylation of eIF2α in CamK2α positive neurons in LA enhanced memory strength, but was accompanied with reduced memory fidelity and behavior inflexibility. Our findings provide evidence for a finely tuned translation program during consolidation of long-term threat memories.

Drug inhibition of memory formation in chickens I. Long-term memory

1971 ◽  
Vol 178 (1053) ◽  
pp. 439-454 ◽  
Keyword(s):  
Protein Synthesis ◽  
Learning Task ◽  
Memory Formation ◽  
Long Term Memory ◽  
Short Term ◽  
Term Memory ◽  
Permanent Storage ◽  
Drug Inhibition ◽  
Two Stages

1. A one-trial passive avoidance learning task using day-old chickens is described and shown to be suitable for testing the effects of direct intracranial injection of drugs. 2. Inhibitors of the sodium pump have been found to block the formation of long-term memory only if present at the time of learning. 3. Inhibitors of protein synthesis will prevent long-term memory formation even if they are administered after learning. 4. From this, there appear to be at least two stages in the formation of memory. A short-term phase dependent on membrane mechanisms leads to permanent storage dependent on protein synthesis.

scholarly journals Learning induces the translin/trax RNase complex to express activin receptors for persistent memory

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Alan Jung Park ◽  
Robbert Havekes ◽  
Xiuping Fu ◽  
Rolf Hansen ◽  
Jennifer C Tudor ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Transforming Growth Factor ◽  
De Novo ◽  
Transforming Growth Factor Β ◽  
Long Term Memory ◽  
The Novel ◽  
Term Memory ◽  
Memory Mechanism ◽  
Β Receptor

Long-lasting forms of synaptic plasticity and memory require de novo protein synthesis. Yet, how learning triggers this process to form memory is unclear. Translin/trax is a candidate to drive this learning-induced memory mechanism by suppressing microRNA-mediated translational silencing at activated synapses. We find that mice lacking translin/trax display defects in synaptic tagging, which requires protein synthesis at activated synapses, and long-term memory. Hippocampal samples harvested from these mice following learning show increases in several disease-related microRNAs targeting the activin A receptor type 1C (ACVR1C), a component of the transforming growth factor-β receptor superfamily. Furthermore, the absence of translin/trax abolishes synaptic upregulation of ACVR1C protein after learning. Finally, synaptic tagging and long-term memory deficits in mice lacking translin/trax are mimicked by ACVR1C inhibition. Thus, we define a new memory mechanism by which learning reverses microRNA-mediated silencing of the novel plasticity protein ACVR1C via translin/trax.

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