scholarly journals Long-Term Memory Deficits in Pavlovian Fear Conditioning in Ca2+/Calmodulin Kinase Kinase α-Deficient Mice

2006 ◽  
Vol 26 (23) ◽  
pp. 9105-9115 ◽  
Author(s):  
Frank Blaeser ◽  
Matthew J. Sanders ◽  
Nga Truong ◽  
Shanelle Ko ◽  
Long Jun Wu ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Long Term Potentiation ◽  
Long Term Memory ◽  
Term Memory ◽  
Calmodulin Kinase ◽  
Element Binding Protein ◽  
Long Term Follow Up ◽  
Responsive Element ◽  
Deficient Mice

ABSTRACT Signaling by the Ca2+/calmodulin kinase (CaMK) cascade has been implicated in neuronal gene transcription, synaptic plasticity, and long-term memory consolidation. The CaM kinase kinase α (CaMKKα) isoform is an upstream component of the CaMK cascade whose function in different behavioral and learning and memory paradigms was analyzed by targeted gene disruption in mice. CaMKKα mutants exhibited normal long-term spatial memory formation and cued fear conditioning but showed deficits in context fear during both conditioning and long-term follow-up testing. They also exhibited impaired activation of the downstream kinase CaMKIV/Gr and its substrate, the transcription factor cyclic AMP-responsive element binding protein (CREB) upon fear conditioning. Unlike CaMKIV/Gr-deficient mice, the CaMKKα mutants exhibited normal long-term potentiation and normal levels of anxiety-like behavior. These results demonstrate a selective role for CaMKKα in contextual fear memory and suggest that different combinations of upstream and downstream components of the CaMK cascade may serve distinct physiological functions.

Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein

Cell ◽  
1994 ◽  
Vol 79 (1) ◽  
pp. 59-68 ◽  
Author(s):  
Roussoudan Bourtchuladze ◽  
Bruno Frenguelli ◽  
Julie Blendy ◽  
Diana Cioffi ◽  
Gunther Schutz ◽  
...  
Keyword(s):  
Binding Protein ◽  
Long Term Memory ◽  
Term Memory ◽  
Targeted Mutation ◽  
Element Binding Protein ◽  
Responsive Element ◽  
Camp Responsive Element Binding

scholarly journals Impaired long-term memory and long-term potentiation in N-type Ca2+channel-deficient mice

2007 ◽  
Vol 6 (4) ◽  
pp. 375-388 ◽  
Author(s):  
D. Jeon ◽  
C. Kim ◽  
Y-M. Yang ◽  
H. Rhim ◽  
E. Yim ◽  
...  
Keyword(s):  
Long Term Potentiation ◽  
Long Term Memory ◽  
Term Memory ◽  
Term Potentiation ◽  
Deficient Mice

scholarly journals Degradation of Transcriptional Repressor ATF4 during Long-Term Synaptic Plasticity

2020 ◽  
Vol 21 (22) ◽  
pp. 8543
Author(s):  
Spencer G. Smith ◽  
Kathryn A. Haynes ◽  
Ashok N. Hegde
Keyword(s):  
Gene Expression ◽  
Synaptic Plasticity ◽  
Transcriptional Repressor ◽  
Long Term Potentiation ◽  
Long Term Memory ◽  
Activating Transcription Factor 4 ◽  
Element Binding Protein ◽  
Activating Transcription Factor ◽  
Responsive Element

Maintenance of long-term synaptic plasticity requires gene expression mediated by cAMP-responsive element binding protein (CREB). Gene expression driven by CREB can commence only if the inhibition by a transcriptional repressor activating transcription factor 4 (ATF4; also known as CREB2) is relieved. Previous research showed that the removal of ATF4 occurs through ubiquitin-proteasome-mediated proteolysis. Using chemically induced hippocampal long-term potentiation (cLTP) as a model system, we investigate the mechanisms that control ATF4 degradation. We observed that ATF4 phosphorylated at serine-219 increases upon induction of cLTP and decreases about 30 min thereafter. Proteasome inhibitor β-lactone prevents the decrease in ATF4. We found that the phosphorylation of ATF4 is mediated by cAMP-dependent protein kinase. Our initial experiments towards the identification of the ligase that mediates ubiquitination of ATF4 revealed a possible role for β-transducin repeat containing protein (β-TrCP). Regulation of ATF4 degradation is likely to be a mechanism for determining the threshold for gene expression underlying maintenance of long-term synaptic plasticity and by extension, long-term memory.

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.

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.

scholarly journals Loss of Ca2+/Calmodulin Kinase Kinase β Affects the Formation of Some, But Not All, Types of Hippocampus-Dependent Long-Term Memory

2003 ◽  
Vol 23 (30) ◽  
pp. 9752-9760 ◽  
Author(s):  
Marco Peters ◽  
Keiko Mizuno ◽  
Laurence Ris ◽  
Marco Angelo ◽  
Emile Godaux ◽  
...  
Keyword(s):  
Long Term Memory ◽  
Term Memory ◽  
Calmodulin Kinase

scholarly journals Meningeal γδ T cell–derived IL-17 controls synaptic plasticity and short-term memory

2019 ◽  
Vol 4 (40) ◽  
pp. eaay5199 ◽  
Author(s):  
Miguel Ribeiro ◽  
Helena C. Brigas ◽  
Mariana Temido-Ferreira ◽  
Paula A. Pousinha ◽  
Tommy Regen ◽  
...  
Keyword(s):  
T Cell ◽  
Short Term Memory ◽  
Long Term Potentiation ◽  
Long Term Memory ◽  
Interleukin 17 ◽  
Γδ T Cell ◽  
Short Term ◽  
Functional Link ◽  
Term Memory

The notion of “immune privilege” of the brain has been revised to accommodate its infiltration, at steady state, by immune cells that participate in normal neurophysiology. However, the immune mechanisms that regulate learning and memory remain poorly understood. Here, we show that noninflammatory interleukin-17 (IL-17) derived from a previously unknown fetal-derived meningeal-resident γδ T cell subset promotes cognition. When tested in classical spatial learning paradigms, mice lacking γδ T cells or IL-17 displayed deficient short-term memory while retaining long-term memory. The plasticity of glutamatergic synapses was reduced in the absence of IL-17, resulting in impaired long-term potentiation in the hippocampus. Conversely, IL-17 enhanced glial cell production of brain-derived neurotropic factor, whose exogenous provision rescued the synaptic and behavioral phenotypes of IL-17–deficient animals. Together, our work provides previously unknown clues on the mechanisms that regulate short-term versus long-term memory and on the evolutionary and functional link between the immune and nervous systems.

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