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’.

scholarly journals The Longevity of Hippocampus-Dependent Memory Is Orchestrated by the Locus Coeruleus-Noradrenergic System

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Niels Hansen
Keyword(s):  
Locus Coeruleus ◽  
Transcriptional Control ◽  
Dorsal Hippocampus ◽  
Long Term Potentiation ◽  
Memory Storage ◽  
Long Term Memory ◽  
Long Term Depression ◽  
Term Potentiation ◽  
Hippocampus Dependent Memory

The locus coeruleus is connected to the dorsal hippocampus via strong fiber projections. It becomes activated after arousal and novelty, whereupon noradrenaline is released in the hippocampus. Noradrenaline from the locus coeruleus is involved in modulating the encoding, consolidation, retrieval, and reversal of hippocampus-based memory. Memory storage can be modified by the activation of the locus coeruleus and subsequent facilitation of hippocampal long-term plasticity in the forms of long-term depression and long-term potentiation. Recent evidence indicates that noradrenaline and dopamine are coreleased in the hippocampus from locus coeruleus terminals, thus fostering neuromodulation of long-term synaptic plasticity and memory. Noradrenaline is an inductor of epigenetic modifications regulating transcriptional control of synaptic long-term plasticity to gate the endurance of memory storage. In conclusion, locus coeruleus activation primes the persistence of hippocampus-based long-term memory.

scholarly journals Evidence of Maintenance Tagging in the Hippocampus for the Persistence of Long-Lasting Memory Storage

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Micol Tomaiuolo ◽  
Cynthia Katche ◽  
Haydee Viola ◽  
Jorge H. Medina
Keyword(s):  
Time Window ◽  
Dorsal Hippocampus ◽  
Training Session ◽  
Critical Time ◽  
Long Term Potentiation ◽  
Memory Storage ◽  
Long Term Memory ◽  
Memory Persistence ◽  
Synaptic Tagging And Capture

The synaptic tagging and capture (STC) hypothesis provides a compelling explanation for synaptic specificity and facilitation of long-term potentiation. Its implication on long-term memory (LTM) formation led to postulate the behavioral tagging mechanism. Here we show that a maintenance tagging process may operate in the hippocampus late after acquisition for the persistence of long-lasting memory storage. The proposed maintenance tagging has several characteristics: (1) the tag is transient and time-dependent; (2) it sets in a late critical time window after an aversive training which induces a short-lasting LTM; (3) exposing rats to a novel environment specifically within this tag time window enables the consolidation to a long-lasting LTM; (4) a familiar environment exploration was not effective; (5) the effect of novelty on the promotion of memory persistence requires dopamine D1/D5 receptors and Arc expression in the dorsal hippocampus. The present results can be explained by a broader version of the behavioral tagging hypothesis and highlight the idea that the durability of a memory trace depends either on late tag mechanisms induced by a training session or on events experienced close in time to this tag.

scholarly journals Integrated Overview of the Memory System

2021 ◽  
Vol 9 (VI) ◽  
pp. 3328-3338
Author(s):  
Ishanee Das Sharma
Keyword(s):  
Molecular Mechanisms ◽  
Short Term Memory ◽  
Long Term Potentiation ◽  
Point Of View ◽  
Memory Storage ◽  
Long Term Memory ◽  
Special Focus ◽  
Term Memory ◽  
Term Potentiation

This review aims to clarify and classify memory from psychological and neuroscientific point of view, delving into the molecular mechanisms taking place as well. The main forms of memory are sensory memory, short term memory and long-term memory. We also try to specify the flow of information through various memory models. The concept of synaptic plasticity and long-term potentiation is highlighted, with special focus on the physiological parts of the brain that are involved in memory storage. Overall, this study will help expand our knowledge on the intrinsic details of memory storage and the functioning of our brain.

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.

scholarly journals Persistent increases of PKMζ in sensorimotor cortex maintain procedural long-term memory storage

2017 ◽  
Author(s):  
Peng P. Gao ◽  
Jeffrey H. Goodman ◽  
Todd C. Sacktor ◽  
Joseph T. Francis
Keyword(s):  
Sensorimotor Cortex ◽  
Primary Motor Cortex ◽  
Long Term Potentiation ◽  
Synaptic Strength ◽  
Procedural Memory ◽  
Memory Storage ◽  
Long Term Memory ◽  
Term Memory ◽  
Atypical Pkc

SummaryProcedural memories, such as for riding a bicycle, can be maintained without practice for long periods of time and are thought to be supported by the persistent reorganization of sensorimotor cortices (S1/M1). Whereas enhanced synaptic strength and structural changes accompany the learning of motor tasks, the persistent molecular modifications that store long-term procedural memories within specific layers of sensorimotor cortex have not been identified. The persistent increase in the autonomously active, atypical PKC isoform, PKMζ, is a putative molecular mechanism for maintaining enhanced synaptic strength during long-term potentiation (LTP) and several forms of long-term memory. Here we examine whether persistent increases in PKMζ store long-term memory for a reaching task in rat sensorimotor cortex that could reveal the sites of procedural memory storage. Perturbing PKMζ synthesis with PKMζ -antisense oligodeoxynucleotides or blocking atypical PKC activity with zeta inhibitory peptide (ZIP) in S1/M1 disrupts and erases the maintenance of long-term motor memories. Only memories that are maintained without daily reinforcement are affected, indicating atypical PKCs (via ZIP) and PKMζ specifically (via antisense) stores consolidated long-term procedural memories. Analysis of changes in the amount of PKMζ in S1/M1 reveals PKMζ increases in layers II/III and V of both S1 and M1 cortices as performance improves to an asymptote during training. After storage for 1 month without reinforcement, the increase in M1 layer V but not other layers persists without decrement. Thus, the sustained increases in PKMζ reveal that the persistent molecular changes storing long-term procedural memory are localized to the descending output layer of primary motor cortex.

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.

scholarly journals Cellular and subcellular localization of PKMζ

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130140 ◽  
Author(s):  
A. Iván Hernández ◽  
William C. Oxberry ◽  
John F. Crary ◽  
Suzanne S. Mirra ◽  
Todd Charlton Sacktor
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Memory Storage ◽  
Long Term Memory ◽  
Electron Microscopic ◽  
Term Memory

In contrast to protein kinases that participate in long-term potentiation (LTP) induction and memory consolidation, the autonomously active atypical protein kinase C isoform, protein kinase Mzeta (PKMζ), functions in the core molecular mechanism of LTP maintenance and long-term memory storage. Here, using multiple complementary techniques for light and electron microscopic immunolocalization, we present the first detailed characterization of the cellular and subcellular distribution of PKMζ in rat hippocampus and neocortex. We find that PKMζ is widely expressed in forebrain with prominent immunostaining in hippocampal and neocortical grey matter, and weak label in white matter. In hippocampal and cortical pyramidal cells, PKMζ expression is predominantly somatodendritic, and electron microscopy highlights the kinase at postsynaptic densities and in clusters within spines. In addition, nuclear label and striking punctate immunopositive structures in a paranuclear and dendritic distribution are seen by confocal microscopy, occasionally at dendritic bifurcations. PKMζ immunoreactive granules are observed by electron microscopy in cell bodies and dendrites, including endoplasmic reticulum. The widespread distribution of PKMζ in nuclei, nucleoli and endoplasmic reticulum suggests potential roles of this kinase in cell-wide mechanisms involving gene expression, biogenesis of ribosomes and new protein synthesis. The localization of PKMζ within postsynaptic densities and spines suggests sites where the kinase stores information during LTP maintenance and long-term memory.

scholarly journals The immediate early gene Arc is not required for hippocampal long-term potentiation

2020 ◽  
Author(s):  
M. Kyrke-Smith ◽  
L.J. Volk ◽  
S.F. Cooke ◽  
M.F. Bear ◽  
R.L. Huganir ◽  
...  
Keyword(s):  
Immediate Early Gene ◽  
Long Term Potentiation ◽  
Memory Storage ◽  
Early Gene ◽  
Immediate Early ◽  
Long Term Memory ◽  
Memory Encoding ◽  
Term Potentiation ◽  
Mrna And Protein Expression

ABSTRACTThe immediate early gene Arc is critical for maintenance of long-term memory. How Arc mediates this process remains unclear, but it has been proposed to sustain Hebbian synaptic potentiation, which is a key component of memory encoding. This form of plasticity is modelled experimentally by induction of long-term potentiation (LTP), which increases Arc mRNA and protein expression. However, mechanistic data implicates Arc in the endocytosis of AMPA-type glutamate receptors and the weakening of synapses. Here, we took a comprehensive approach to determine if Arc is necessary for hippocampal LTP. We find that Arc is not required for LTP maintenance and must regulate memory storage through alternative mechanisms.

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