scholarly journals The biophysical basis underlying the maintenance of early phase long-term potentiation

2020 ◽  
Author(s):  
Moritz F. P. Becker ◽  
Christian Tetzlaff
Keyword(s):  
Receptor Binding ◽  
Early Phase ◽  
Morphological Changes ◽  
Long Term Potentiation ◽  
Biophysical Model ◽  
Recycling Endosomes ◽  
Term Potentiation ◽  
Wide Range ◽  
Synaptic Changes

AbstractThe maintenance of synaptic changes resulting from long-term potentiation (LTP) is essential for brain function such as memory and learning. Different LTP phases have been associated with diverse molecular processes and pathways, and the molecular underpinnings of LTP on the short, as well as long time scales, are well established. However, the principles on the intermediate time scale of 1-6 hours that mediate the early phase of LTP (E-LTP) remain elusive. We hypothesize that the interplay between specific features of postsynaptic receptor trafficking is responsible for sustaining synaptic changes during this LTP phase. We test this hypothesis by formalizing a biophysical model that integrates several experimentally-motivated mechanisms. The model captures a wide range of experimental findings and predicts that synaptic changes are preserved for hours when the receptor dynamics are shaped by the interplay of structural changes of the spine in conjunction with increased trafficking from recycling endosomes and the cooperative binding of receptors. Furthermore, our model provides several predictions to verify our findings experimentally.Author summaryThe cognitive ability of learning is associated with plasticity-induced changes in synaptic transmission efficacy mediated by AMPA receptors. Synaptic changes depend on a multitude of molecular and physiological mechanisms, building complex interaction networks. By formalizing and employing a biophysical model of AMPAR trafficking, we unravel and evaluate the interplay between key mechanisms such as receptor binding, exocytosis, morphological changes, and cooperative receptor binding. Our findings indicate that cooperative receptor binding in conjunction with morphological changes of the spine and increased trafficking from recycling endosomes leads to the maintenance of synaptic changes on behaviorally relevant time spans. Characterizing the principles underlying synaptic changes will provide insight into the role of synaptic dynamics in neurodegenerative diseases.

scholarly journals The biophysical basis underlying the maintenance of early phase long-term potentiation

2021 ◽  
Vol 17 (3) ◽  
pp. e1008813
Author(s):  
Moritz F. P. Becker ◽  
Christian Tetzlaff
Keyword(s):  
Early Phase ◽  
Structural Changes ◽  
Long Term Potentiation ◽  
Biophysical Model ◽  
Term Potentiation ◽  
Wide Range ◽  
Long Time ◽  
Synaptic Changes ◽  
Experimental Findings

The maintenance of synaptic changes resulting from long-term potentiation (LTP) is essential for brain function such as memory and learning. Different LTP phases have been associated with diverse molecular processes and pathways, and the molecular underpinnings of LTP on the short, as well as long time scales, are well established. However, the principles on the intermediate time scale of 1-6 hours that mediate the early phase of LTP (E-LTP) remain elusive. We hypothesize that the interplay between specific features of postsynaptic receptor trafficking is responsible for sustaining synaptic changes during this LTP phase. We test this hypothesis by formalizing a biophysical model that integrates several experimentally-motivated mechanisms. The model captures a wide range of experimental findings and predicts that synaptic changes are preserved for hours when the receptor dynamics are shaped by the interplay of structural changes of the spine in conjunction with increased trafficking from recycling endosomes and the cooperative binding of receptors. Furthermore, our model provides several predictions to verify our findings experimentally.

scholarly journals Stress enhances fear by forming new synapses with greater capacity for long-term potentiation in the amygdala

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130151 ◽  
Author(s):  
Aparna Suvrathan ◽  
Sharath Bennur ◽  
Supriya Ghosh ◽  
Anupratap Tomar ◽  
Shobha Anilkumar ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Conditioned Fear ◽  
Brain Area ◽  
Long Term Potentiation ◽  
Silent Synapses ◽  
Term Potentiation ◽  
Emotional Behaviour ◽  
Synaptic Changes ◽  
And Function

Prolonged and severe stress leads to cognitive deficits, but facilitates emotional behaviour. Little is known about the synaptic basis for this contrast. Here, we report that in rats subjected to chronic immobilization stress, long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated synaptic responses are enhanced in principal neurons of the lateral amygdala, a brain area involved in fear memory formation. This is accompanied by electrophysiological and morphological changes consistent with the formation of ‘silent synapses’, containing only NMDARs. In parallel, chronic stress also reduces synaptic inhibition. Together, these synaptic changes would enable amygdalar neurons to undergo further experience-dependent modifications, leading to stronger fear memories. Consistent with this prediction, stressed animals exhibit enhanced conditioned fear. Hence, stress may leave its mark in the amygdala by generating new synapses with greater capacity for plasticity, thereby creating an ideal neuronal substrate for affective disorders. These findings also highlight the unique features of stress-induced plasticity in the amygdala that are strikingly different from the stress-induced impairment of structure and function in the hippocampus.

Expression of Bcl2 Family Genes in the Early Phase of Long-Term Potentiation

2014 ◽  
Vol 158 (1) ◽  
pp. 77-79 ◽  
Author(s):  
P. D. Lisachev ◽  
V. O. Pustyl’nyak ◽  
M. B. Shtark
Keyword(s):  
Early Phase ◽  
Long Term Potentiation ◽  
Bcl2 Family ◽  
Term Potentiation

Klk8, a multifunctional protease in the brain and skin: analysis of knockout mice

2010 ◽  
Vol 391 (4) ◽  
Author(s):  
Shigetaka Yoshida
Keyword(s):  
Central Nervous System ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
The Central Nervous System ◽  
Synaptic Changes ◽  
Adhesive Molecules ◽  
High Level ◽  
Activity Dependent ◽  
The Brain

Abstract Klk8 is a tryptic serine protease with limited substrate specificity. Klk8 mRNA is expressed in many developing organs, whereas its expression is confined to limited regions, including the hippocampus, in adults. In the hippocampus, Klk8 is involved in activity-dependent synaptic changes such as long-term potentiation, which was found to be suppressed in Klk8 knockout (KO) mice. Oligodendrocytes only expressed Klk8 mRNA after injury to the central nervous system. The epidermis of the skin is one of the tissues that exhibits a high level of KLK8 expression. Klk8 might be involved in desquamation through the degradation of adhesive molecules that connect layers of the epidermis. Klk8 might thus be involved in tissue development and rearrangement.

[P4-036]: THE NOVEL AMPA RECEPTOR POSITIVE ALLOSTERIC MODULATOR S 47445 RESCUES IN VIVO CA3-CA1 LONG-TERM POTENTIATION AND STRUCTURAL SYNAPTIC CHANGES IN MIDDLE-AGED MICE

2017 ◽  
Vol 13 (7S_Part_26) ◽  
pp. P1270-P1270
Author(s):  
Sylvie Bretin ◽  
Albert Giralt ◽  
María Ángeles Gómez-Climent ◽  
Rafael Alcalá ◽  
Jose Maria Delgado-Garcia ◽  
...  
Keyword(s):  
Ampa Receptor ◽  
Long Term Potentiation ◽  
Allosteric Modulator ◽  
The Novel ◽  
Positive Allosteric Modulator ◽  
Aged Mice ◽  
Term Potentiation ◽  
Synaptic Changes

scholarly journals Endophilin A1 promotes Actin Polymerization in response to Ca2+/calmodulin to Initiate Structural Plasticity of Dendritic Spines

2020 ◽  
Author(s):  
Yanrui Yang ◽  
Jiang Chen ◽  
Xue Chen ◽  
Di Li ◽  
Jianfeng He ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Actin Polymerization ◽  
Morphological Changes ◽  
Structural Plasticity ◽  
Long Term Potentiation ◽  
Membrane Dynamics ◽  
Long Term Memory ◽  
Induction Phase ◽  
Term Potentiation

AbstractDendritic spines of excitatory neurons undergo activity-dependent structural and functional plasticity, which are cellular correlates of learning and memory. However, mechanisms underlying the rapid morphological changes immediately after NMDAR-mediated Ca2+ influx into spines remain poorly understood. Here we report that endophilin A1, a neuronal N-BAR protein, orchestrates membrane dynamics with actin polymerization to initiate spine enlargement in the induction phase of long-term potentiation (LTP). Upon LTP induction, Ca2+/calmodulin enhances its binding to both membrane and p140Cap, a cytoskeleton regulator. As a result, endophilin A1 rapidly associates with the relaxed plasma membrane and promotes actin polymerization, leading to acute expansion of spine head. Moreover, not only the p140Cap-binding, but also calmodulin- and membrane-binding capacities of endophilin A1 are required for LTP and long-term memory. Thus, endophilin A1 functions as calmodulin effector to drive spine enlargement in response to Ca2+ influx in the initial phase of structural plasticity.

A Statistical Theory of Long-Term Potentiation and Depression

2001 ◽  
Vol 13 (1) ◽  
pp. 87-111 ◽  
Author(s):  
John M. Beggs
Keyword(s):  
Response Curve ◽  
Long Term Potentiation ◽  
Synaptic Strength ◽  
Excitatory Synapses ◽  
Field Potentials ◽  
Postsynaptic Activity ◽  
Term Potentiation ◽  
Synaptic Changes ◽  
Cortical Slices

The synaptic phenomena of long-term potentiation (LTP) and long-term depression (LTD) have been intensively studied for over twenty-five years. Although many diverse aspects of these forms of plasticity have been observed, no single theory has offered a unifying explanation for them. Here, a statistical “bin” model is proposed to account for a variety of features observed in LTP and LTD experiments performed with field potentials in mammalian cortical slices. It is hypothesized that long-term synaptic changes will be induced when statistically unlikely conjunctions of pre- and postsynaptic activity occur. This hypothesis implies that finite changes in synaptic strength will be proportional to information transmitted by conjunctions and that excitatory synapses will obey a Hebbian rule (Hebb, 1949). Using only one set of constants, the bin model offers an explanation as to why synaptic strength decreases in a decelerating manner during LTD induction (Mulkey & Malenka, 1992); why the induction protocols for LTP and LTD are asymmetric (Dudek & Bear, 1992; Mulkey & Malenka, 1992); why stimulation over a range of frequencies produces a frequency-response curve similar to that proposed by the BCM theory (Bienenstock, Cooper, & Munro, 1982; Dudek & Bear, 1992); and why this curve would shift as postsynaptic activity is changed (Kirkwood, Rioult, & Bear, 1996). In addition, the bin model offers an alternative to the BCM theory by predicting that changes in postsynaptic activity will produce vertical shifts in the curve rather than merely horizontal shifts.

scholarly journals Synaptic activity regulates AMPA receptor trafficking through different recycling pathways

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Ning Zheng ◽  
Okunola Jeyifous ◽  
Charlotte Munro ◽  
Johanna M Montgomery ◽  
William N Green
Keyword(s):  
Long Term Potentiation ◽  
Receptor Trafficking ◽  
Synaptic Activity ◽  
Transferrin Receptors ◽  
Long Term Depression ◽  
Recycling Endosomes ◽  
Surface Receptors ◽  
Term Potentiation ◽  
Dependent Pathway

Changes in glutamatergic synaptic strength in brain are dependent on AMPA-type glutamate receptor (AMPAR) recycling, which is assumed to occur through a single local pathway. In this study, we present evidence that AMPAR recycling occurs through different pathways regulated by synaptic activity. Without synaptic stimulation, most AMPARs recycled in dynamin-independent endosomes containing the GTPase, Arf6. Few AMPARs recycled in dynamin-dependent endosomes labeled by transferrin receptors (TfRs). AMPAR recycling was blocked by alterations in the GTPase, TC10, which co-localized with Arf6 endosomes. TC10 mutants that reduced AMPAR recycling had no effect on increased AMPAR levels with long-term potentiation (LTP) and little effect on decreased AMPAR levels with long-term depression. However, internalized AMPAR levels in TfR-containing recycling endosomes increased after LTP, indicating increased AMPAR recycling through the dynamin-dependent pathway with synaptic plasticity. LTP-induced AMPAR endocytosis is inconsistent with local recycling as a source of increased surface receptors, suggesting AMPARs are trafficked from other sites.

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