scholarly journals Protein Synthesis Is Required for the Enhancement of Long-Term Potentiation and Long-Term Memory by Spaced Training

2002 ◽  
Vol 87 (6) ◽  
pp. 2770-2777 ◽  
Author(s):  
Matthew T. Scharf ◽  
Newton H. Woo ◽  
K. Matthew Lattal ◽  
Jennie Z. Young ◽  
Peter V. Nguyen ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Spacing Effect ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Mammalian Brain ◽  
Long Term Memory ◽  
Behavioral Training ◽  
Term Memory ◽  
Trial Spacing

Spaced training is generally more effective than massed training for learning and memory, but the molecular mechanisms underlying this trial spacing effect remain poorly characterized. One potential molecular basis for the trial spacing effect is the differential modulation, by distinct temporal patterns of neuronal activity, of protein synthesis-dependent processes that contribute to the expression of specific forms of synaptic plasticity in the mammalian brain. Long-term potentiation (LTP) is a type of synaptic modification that may be important for certain forms of memory storage in the mammalian brain. To explore the role of protein synthesis in the trial spacing effect, we assessed the protein synthesis dependence of hippocampal LTP induced by 100-Hz tetraburst stimulation delivered to mouse hippocampal slices in either a temporally massed (20-s interburst interval) or spaced (5-min interburst interval) fashion. To extend our studies to the behavioral level, we trained mice in fear conditioning using either a massed or spaced training protocol and examined the sensitivity of long-term memory to protein synthesis inhibition. Larger LTP was induced by spaced stimulation in hippocampal slices. This improvement of synaptic potentiation following temporally spaced synaptic stimulation in slices was attenuated by bath application of an inhibitor of protein synthesis. Further, the maintenance of LTP induced by spaced synaptic stimulation was more sensitive to disruption by anisomycin than the maintenance of LTP elicited following massed stimulation. Temporally spaced behavioral training improved long-term memory for contextual but not for cued fear conditioning, and this enhancement of memory for contextual fear was also protein synthesis dependent. Our data reveal that altering the temporal spacing of synaptic stimulation and behavioral training improved hippocampal LTP and enhanced contextual long-term memory. From a broad perspective, these results suggest that the recruitment of protein synthesis-dependent processes important for long-term memory and for long-lasting forms of LTP can be modulated by the temporal profiles of behavioral training and synaptic stimulation.

Temporal phases of long-term potentiation (LTP): myth or fact?

2015 ◽  
Vol 26 (5) ◽  
pp. 507-546 ◽  
Author(s):  
Abdul-Karim Abbas ◽  
Agnès Villers ◽  
Laurence Ris
Keyword(s):  
Protein Synthesis ◽  
De Novo ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Long Term Memory ◽  
Protein Synthesis Inhibitor ◽  
Protein Synthesis Inhibitors ◽  
Early Protein ◽  
Term Potentiation

AbstractLong-term potentiation (LTP) remains the most widely accepted model for learning and memory. In accordance with this belief, the temporal differentiation of LTP into early and late phases is accepted as reflecting the differentiation of short-term and long-term memory. Moreover, during the past 30 years, protein synthesis inhibitors have been used to separate the early, protein synthesis-independent (E-LTP) phase and the late, protein synthesis-dependent (L-LTP) phase. However, the role of these proteins has not been formally identified. Additionally, several reports failed to show an effect of protein synthesis inhibitors on LTP. In this review, a detailed analysis of extensive behavioral and electrophysiological data reveals that the presumed correspondence of LTP temporal phases to memory phases is neither experimentally nor theoretically consistent. Moreover, an overview of the time courses of E-LTP in hippocampal slices reveals a wide variability ranging from <1 h to more than 5 h. The existence of all these conflictual findings should lead to a new vision of LTP. We believe that the E-LTP vs. L-LTP distinction, established with protein synthesis inhibitor studies, reflects a false dichotomy. We suggest that the duration of LTP and its dependency on protein synthesis are related to the availability of a set of proteins at synapses and not to the de novo synthesis of plasticity-related proteins. This availability is determined by protein turnover kinetics, which is regulated by previous and ongoing electrical activities and by energy store availability.

scholarly journals PKMζ traces hippocampal LTP maintenance and spatial long-term memory

2020 ◽  
Author(s):  
Changchi Hsieh ◽  
Panayiotis Tsokas ◽  
Ain Chung ◽  
Claudia Garcia-Jou ◽  
Edith Lesburguères ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Hippocampal Formation ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Memory Storage ◽  
Long Term Memory ◽  
Term Memory ◽  
Ca1 Pyramidal Cells

PKMζ is an autonomously active, atypical PKC isoform crucial for maintaining synaptic long-term potentiation (LTP) and long-term memory. Unlike other PKCs that are transiently activated by short-lived second messengers, PKMζ is persistently activated by long-lasting increases in the amount of the autonomously active kinase during LTP and long-term memory maintenance. Thus, localizing persistent increases in PKMζ might reveal traces of physiological LTP maintenance in the circuitry of the brain during long-term memory storage. Using quantitative immunohistochemistry validated by the lack of staining in PKMζ-null mice, we visualized the amount and distribution of PKMζ during LTP maintenance and spatial long-term memory storage in the hippocampal formation of wild-type mice. Strong afferent stimulation of Schaffer collateral/commissural fibers inducing LTP maintenance increases PKMζ in CA1 pyramidal cells for 2 hours in hippocampal slices. Active place avoidance spatial conditioning increases PKMζ in CA1 pyramidal cells of the hippocampal formation from 1 day to at least 1 month. The increases in PKMζ coincide with the location of cells marked during long-term memory training by Arc promoter-mediated expression of a fluorescent protein, including at dendritic spines. We conclude that increased PKMζ forms persistent traces in CA1 pyramidal cells that are sites of molecular information storage during LTP maintenance and spatial long-term memory.Graphical AbstractPKMζ-immunohistochemistry reveals persistent increased PKMζ in the hippocampus during (A) LTP maintenance, and (B) spatial long-term memory storage.

The role of PKMζ in the maintenance of long-term memory: a review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hamish Patel ◽  
Reza Zamani
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Long Term Potentiation ◽  
Global Memory ◽  
Long Term Memory ◽  
Compensatory Mechanism ◽  
Term Memory ◽  
Kinase C

Abstract Long-term memories are thought to be stored in neurones and synapses that undergo physical changes, such as long-term potentiation (LTP), and these changes can be maintained for long periods of time. A candidate enzyme for the maintenance of LTP is protein kinase M zeta (PKMζ), a constitutively active protein kinase C isoform that is elevated during LTP and long-term memory maintenance. This paper reviews the evidence and controversies surrounding the role of PKMζ in the maintenance of long-term memory. PKMζ maintains synaptic potentiation by preventing AMPA receptor endocytosis and promoting stabilisation of dendritic spine growth. Inhibition of PKMζ, with zeta-inhibitory peptide (ZIP), can reverse LTP and impair established long-term memories. However, a deficit of memory retrieval cannot be ruled out. Furthermore, ZIP, and in high enough doses the control peptide scrambled ZIP, was recently shown to be neurotoxic, which may explain some of the effects of ZIP on memory impairment. PKMζ knockout mice show normal learning and memory. However, this is likely due to compensation by protein-kinase C iota/lambda (PKCι/λ), which is normally responsible for induction of LTP. It is not clear how, or if, this compensatory mechanism is activated under normal conditions. Future research should utilise inducible PKMζ knockdown in adult rodents to investigate whether PKMζ maintains memory in specific parts of the brain, or if it represents a global memory maintenance molecule. These insights may inform future therapeutic targets for disorders of memory loss.

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 Memory Consolidation for Contextual and Auditory Fear Conditioning Is Dependent on Protein Synthesis, PKA, and MAP Kinase

1999 ◽  
Vol 6 (2) ◽  
pp. 97-110 ◽  
Author(s):  
Glenn E. Schafe ◽  
Nicole V. Nadel ◽  
Gregory M. Sullivan ◽  
Alexander Harris ◽  
Joseph E. LeDoux
Keyword(s):  
Protein Synthesis ◽  
Map Kinase ◽  
Fear Conditioning ◽  
Memory Consolidation ◽  
Molecular Mechanisms ◽  
Short Term Memory ◽  
Long Term Potentiation ◽  
Fear Memory ◽  
Term Memory

Fear conditioning has received extensive experimental attention. However, little is known about the molecular mechanisms that underlie fear memory consolidation. Previous studies have shown that long-term potentiation (LTP) exists in pathways known to be relevant to fear conditioning and that fear conditioning modifies neural processing in these pathways in a manner similar to LTP induction. The present experiments examined whether inhibition of protein synthesis, PKA, and MAP kinase activity, treatments that block LTP, also interfere with the consolidation of fear conditioning. Rats were injected intraventricularly with Anisomycin (100 or 300 μg), Rp-cAMPS (90 or 180 μg), or PD098059 (1 or 3 μg) prior to conditioning and assessed for retention of contextual and auditory fear memory both within an hour and 24 hr later. Results indicated that injection of these compounds selectively interfered with long-term memory for contextual and auditory fear, while leaving short-term memory intact. Additional control groups indicated that this effect was likely due to impaired memory consolidation rather than to nonspecific effects of the drugs on fear expression. Results suggest that fear conditioning and LTP may share common molecular mechanisms.

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