scholarly journals LIMK1 Regulates Long-Term Memory and Synaptic Plasticity via the Transcriptional Factor CREB

2015 ◽  
Vol 35 (8) ◽  
pp. 1316-1328 ◽  
Author(s):  
Zarko Todorovski ◽  
Suhail Asrar ◽  
Jackie Liu ◽  
Ner Mu Nar Saw ◽  
Krutika Joshi ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Williams Syndrome ◽  
Neurodevelopmental Disorder ◽  
Late Phase ◽  
Long Term Potentiation ◽  
Transcriptional Factor ◽  
Adult Brain ◽  
Long Term Memory ◽  
Term Memory

Deletion of theLIMK1gene is associated with Williams syndrome, a unique neurodevelopmental disorder characterized by severe defects in visuospatial cognition and long-term memory (LTM). However, whether LIMK1 contributes to these deficits remains elusive. Here, we show that LIMK1-knockout (LIMK1−/−) mice are drastically impaired in LTM but not short-term memory (STM). In addition, LIMK1−/−mice are selectively defective in late-phase long-term potentiation (L-LTP), a form of long-lasting synaptic plasticity specifically required for the formation of LTM. Furthermore, we show that LIMK1 interacts and regulates the activity of cyclic AMP response element-binding protein (CREB), an extensively studied transcriptional factor critical for LTM. Importantly, both L-LTP and LTM deficits in LIMK1−/−mice are rescued by increasing the activity of CREB. These results provide strong evidence thatLIMK1deletion is sufficient to lead to an LTM deficit and that this deficit is attributable to CREB hypofunction. Our study has identified a direct gene-phenotype link in mice and provides a potential strategy to restore LTM in patients with Williams syndrome through the enhancement of CREB activity in the adult brain.

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 Calcium-Stimulated Adenylyl Cyclase Activity Is Critical for Hippocampus-Dependent Long-Term Memory and Late Phase LTP

Neuron ◽  
1999 ◽  
Vol 23 (4) ◽  
pp. 787-798 ◽  
Author(s):  
Scott T Wong ◽  
Jaime Athos ◽  
Xavier A Figueroa ◽  
Victor V Pineda ◽  
Michele L Schaefer ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Late Phase ◽  
Cyclase Activity ◽  
Long Term Memory ◽  
Adenylyl Cyclase Activity ◽  
Term Memory

Estrogenic Regulation of Synaptic Actin Proteins and Plasticity

2020 ◽  
pp. 69-82
Author(s):  
Enikö A. Kramár
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Synaptic Strength ◽  
Adult Brain ◽  
Actin Dynamics ◽  
Signaling Cascade ◽  
Term Potentiation ◽  
Estrogenic Regulation ◽  
Estradiol Levels

Estrogens are rapid and potent facilitators of synaptic plasticity in the adult brain; however, the steps that link estrogens to factors that regulate synaptic strength remain unclear. The present chapter will first review the acute effects of 17β‎-estradiol on synaptic transmission and long-term potentiation (LTP). It will then describe a synaptic model used to study the substrates of LTP and provide evidence for the ability of estradiol to rapidly engage a selective actin signaling cascade associated with the consolidation of LTP. Finally, it will be shown that chronic reductions in estradiol levels disrupt LTP and actin dynamics but can be reversed by acute infusions of the hormone. It is concluded here that estradiol can promote learning-related plasticity by modifying the synaptic cytoskeleton.

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.

scholarly journals Gradation (approx. 10 size states) of synaptic strength by quantal addition of structural modules

2017 ◽  
Vol 372 (1715) ◽  
pp. 20160328 ◽  
Author(s):  
Kang K. L. Liu ◽  
Michael F. Hagan ◽  
John E. Lisman
Keyword(s):  
Functional Module ◽  
Late Phase ◽  
Matrix Material ◽  
Super Resolution ◽  
Long Term Potentiation ◽  
Information Storage ◽  
Homeostatic Plasticity ◽  
Memory Storage ◽  
Long Term Memory

Memory storage involves activity-dependent strengthening of synaptic transmission, a process termed long-term potentiation (LTP). The late phase of LTP is thought to encode long-term memory and involves structural processes that enlarge the synapse. Hence, understanding how synapse size is graded provides fundamental information about the information storage capability of synapses. Recent work using electron microscopy (EM) to quantify synapse dimensions has suggested that synapses may structurally encode as many as 26 functionally distinct states, which correspond to a series of proportionally spaced synapse sizes. Other recent evidence using super-resolution microscopy has revealed that synapses are composed of stereotyped nanoclusters of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and scaffolding proteins; furthermore, synapse size varies linearly with the number of nanoclusters. Here we have sought to develop a model of synapse structure and growth that is consistent with both the EM and super-resolution data. We argue that synapses are composed of modules consisting of matrix material and potentially one nanocluster. LTP induction can add a trans-synaptic nanocluster to a module, thereby converting a silent module to an AMPA functional module. LTP can also add modules by a linear process, thereby producing an approximately 10-fold gradation in synapse size and strength. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.

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