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.

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

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.

Hippocampal long term memory: Effect of the cholinergic system on local protein synthesis

2013 ◽  
Vol 106 ◽  
pp. 246-257 ◽  
Author(s):  
Daniele Lana ◽  
Francesca Cerbai ◽  
Jacopo Di Russo ◽  
Francesca Boscaro ◽  
Ambra Giannetti ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Memory Effect ◽  
Cholinergic System ◽  
Long Term Memory ◽  
Term Memory ◽  
Local Protein Synthesis ◽  
Local Protein

scholarly journals Protein synthesis required for long-term memory is induced by PKC activation on days before associative learning

2005 ◽  
Vol 102 (45) ◽  
pp. 16432-16437 ◽  
Author(s):  
D. L. Alkon ◽  
H. Epstein ◽  
A. Kuzirian ◽  
M. C. Bennett ◽  
T. J. Nelson
Keyword(s):  
Protein Synthesis ◽  
Associative Learning ◽  
Long Term Memory ◽  
Term Memory ◽  
Pkc Activation

scholarly journals Long-term memory requires sequential protein synthesis in three subsets of mushroom body output neurons in Drosophila

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jie-Kai Wu ◽  
Chu-Yi Tai ◽  
Kuan-Lin Feng ◽  
Shiu-Ling Chen ◽  
Chun-Chao Chen ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mushroom Body ◽  
Long Term Memory ◽  
Term Memory ◽  
Output Neurons

scholarly journals The amnestic agent anisomycin disrupts intrinsic membrane properties of hippocampal neurons via a loss of cellular energetics

2019 ◽  
Vol 122 (3) ◽  
pp. 1123-1135 ◽  
Author(s):  
C. J. Scavuzzo ◽  
M. J. LeBlancq ◽  
F. Nargang ◽  
H. Lemieux ◽  
T. J. Hamilton ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mitochondrial Function ◽  
Neural Activity ◽  
Memory Consolidation ◽  
Hippocampal Neurons ◽  
Membrane Properties ◽  
Long Term Memory ◽  
Term Memory ◽  
Cellular Energetics

The nearly axiomatic idea that de novo protein synthesis is necessary for long-term memory consolidation is based heavily on behavioral studies using translational inhibitors such as anisomycin. Although inhibiting protein synthesis has been shown to disrupt the expression of memory, translational inhibitors also have been found to profoundly disrupt basic neurobiological functions, including the suppression of ongoing neural activity in vivo. In the present study, using transverse hippocampal brain slices, we monitored the passive and active membrane properties of hippocampal CA1 pyramidal neurons using intracellular whole cell recordings during a brief ~30-min exposure to fast-bath-perfused anisomycin. Anisomycin suppressed protein synthesis to 46% of control levels as measured using incorporation of radiolabeled amino acids and autoradiography. During its application, anisomycin caused a significant depolarization of the membrane potential, without any changes in apparent input resistance or membrane time constant. Anisomycin-treated neurons also showed significant decreases in firing frequencies and spike amplitudes, and showed increases in spike width across spike trains, without changes in spike threshold. Because these changes indicated a loss of cellular energetics contributing to maintenance of ionic gradients across the membrane, we confirmed that anisomycin impaired mitochondrial function by reduced staining with 2,3,5-triphenyltetrazolium chloride and also impaired cytochrome c oxidase (complex IV) activity as indicated through high-resolution respirometry. These findings emphasize that anisomycin-induced alterations in neural activity and metabolism are a likely consequence of cell-wide translational inhibition. Critical reevaluation of studies using translational inhibitors to promote the protein synthesis dependent idea of long-term memory is absolutely necessary. NEW & NOTEWORTHY Memory consolidation is thought to be dependent on the synthesis of new proteins because translational inhibitors produce amnesia when administered just after learning. However, these agents also disrupt basic neurobiological functions. We show that blocking protein synthesis disrupts basic membrane properties of hippocampal neurons that correspond to induced disruptions of mitochondrial function. It is likely that translational inhibitors cause amnesia through their disruption of neural activity as a result of dysfunction of intracellular energetics.

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