scholarly journals Membrane Remodeling by Arc/Arg3.1

2021 ◽  
Vol 8 ◽  
Author(s):  
Per Niklas Hedde ◽  
Leonel Malacrida ◽  
Barbara Barylko ◽  
Derk D. Binns ◽  
Joseph P. Albanesi ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Terminal Segment ◽  
Membrane Curvature ◽  
Early Gene ◽  
Striking Similarity ◽  
Term Potentiation ◽  
Membrane Budding

The activity-regulated cytoskeletal-associated protein (Arc, also known as Arg3.1) is an immediate early gene product induced by activity/experience and required for multiple modes of synaptic plasticity. Both long-term potentiation (LTP) and long-term depression (LTD) are impaired upon Arc deletion, as well as the ability to form long-term spatial, taste and fear memories. The best-characterized cellular function of Arc is enhancement of the endocytic internalization of AMPA receptors (AMPARs) in dendritic spines. Solution of the crystal structure of a C-terminal segment of Arc revealed a striking similarity to the capsid domain of HIV Gag. It was subsequently shown that Arc assembles into viral capsid-like structures that enclose Arc mRNA, are released into the extracellular space, and are internalized by neighboring cells. Thus, Arc is unique in participating in plasma membrane budding both into and out of the cell. In this report we study the interaction of Arc with membranes using giant unilamellar vesicles (GUVs). Using the fluorescent lipid probe LAURDAN, we find that Arc promotes the formation of smaller vesicles that penetrate into the GUV interior. Our results suggest that Arc induces negative membrane curvature and may therefore facilitate the formation of mRNA-containing extracellular vesicles from the plasma membrane.

scholarly journals PKA drives an increase in AMPA receptor unitary conductance during LTP in the hippocampus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pojeong Park ◽  
John Georgiou ◽  
Thomas M. Sanderson ◽  
Kwang-Hee Ko ◽  
Heather Kang ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Single Channel ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Theta Burst Stimulation ◽  
Term Potentiation ◽  
Hippocampal Ca1 ◽  
Necessary And Sufficient ◽  
Theta Burst

AbstractLong-term potentiation (LTP) at hippocampal CA1 synapses can be expressed by an increase either in the number (N) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors or in their single channel conductance (γ). Here, we have established how these distinct synaptic processes contribute to the expression of LTP in hippocampal slices obtained from young adult rodents. LTP induced by compressed theta burst stimulation (TBS), with a 10 s inter-episode interval, involves purely an increase in N (LTPN). In contrast, either a spaced TBS, with a 10 min inter-episode interval, or a single TBS, delivered when PKA is activated, results in LTP that is associated with a transient increase in γ (LTPγ), caused by the insertion of calcium-permeable (CP)-AMPA receptors. Activation of CaMKII is necessary and sufficient for LTPN whilst PKA is additionally required for LTPγ. Thus, two mechanistically distinct forms of LTP co-exist at these synapses.

scholarly journals Selective increase of functional network connectivity in Arc-positive neuronal engrams after long-term potentiation

2020 ◽  
Author(s):  
Yuheng Jiang ◽  
Antonius M.J. VanDongen
Keyword(s):  
Functional Connectivity ◽  
Hippocampal Neurons ◽  
Network Effects ◽  
Network Connectivity ◽  
Long Term Potentiation ◽  
Early Gene ◽  
Memory Traces ◽  
Term Potentiation ◽  
Memory Engram

ABSTRACTNew tools in optogenetics and molecular biology have culminated in recent studies which mark immediate-early gene (IEG)-expressing neurons as memory traces or engrams. Although the activity-dependent expression of IEGs has been successfully utilised to label memory traces, their roles in engram specification is incompletely understood. Outstanding questions remain as to whether expression of IEGs can interplay with network properties such as functional connectivity and also if neurons expressing different IEGs are functionally distinct. We investigated the expression of Arc and c-Fos, two commonly utilised IEGs in memory engram specification, in cultured hippocampal neurons. After pharmacological induction of long-term potentiation (LTP) in the network, we noted an emergent network property of refinement in functional connectivity between neurons, characterized by a global down-regulation of network connectivity, together with strengthening of specific connections. Subsequently, we show that Arc expression correlates with the effects of network refinement, with Arc-positive neurons being selectively strengthened. Arc positive neurons were also found to be located in closer physical proximity to each other in the network. While the expression pattern of IEGs c-Fos and Arc strongly overlaps, Arc was more selectively expressed than c-Fos. These IEGs also act together in coding information about connection strength pruning. These results demonstrate important links between IEG expression and network connectivity, which serve to bridge the gap between cellular correlates and network effects in learning and memory.

scholarly journals Silent synapses: what are they telling us about long-term potentiation?

2003 ◽  
Vol 358 (1432) ◽  
pp. 727-733 ◽  
Author(s):  
Dimitri M. Kullmann
Keyword(s):  
Ampa Receptors ◽  
Hippocampal Neurons ◽  
Glutamate Release ◽  
Postsynaptic Density ◽  
Long Term Potentiation ◽  
Silent Synapses ◽  
Term Potentiation ◽  
Silent Synapse ◽  
Cortical Synapses

At several cortical synapses glutamate release events can be mediated exclusively by NMDA receptors, with no detectable contribution from AMPA receptors. This observation was originally made by comparing the trial-to-trial variability of the two components of synaptic signals evoked in hippocampal neurons, and was subsequently confirmed by recording apparently pure NMDA receptor-mediated EPSCs with stimulation of small numbers of axons. It has come to be known as the ‘silent synapse’ phenomenon, and is widely assumed to be caused by the absence of functional AMPA receptors, which can, however, be recruited into the postsynaptic density by long-term potentiation (LTP) induction. Thus, it provides an important impetus for relating AMPA receptor trafficking mechanisms to the expression of LTP, a theme that is taken up elsewhere in this issue. This article draws attention to several findings that call for caution in identifying silent synapses exclusively with synapses without AMPA receptors. In addition, it attempts to identify several missing pieces of evidence that are required to show that unsilencing of such synapses is entirely accounted for by insertion of AMPA receptors into the postsynaptic density. Some aspects of the early stages of LTP expression remain open to alternative explanations.

Tissue-plasminogen activator is induced as an immediate–early gene during seizure, kindling and long-term potentiation

Nature ◽  
1993 ◽  
Vol 361 (6411) ◽  
pp. 453-457 ◽  
Author(s):  
Zhuo Qian ◽  
Mary E. Gilbert ◽  
Michael A. Colicos ◽  
Eric R. Kandel ◽  
Dietmar Kuhl
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Immediate Early Gene ◽  
Long Term Potentiation ◽  
Early Gene ◽  
Immediate Early ◽  
Term Potentiation ◽  
Tissue Plasminogen

scholarly journals Moderate AMPA receptor clustering on the nanoscale can efficiently potentiate synaptic current

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130167 ◽  
Author(s):  
Leonid P. Savtchenko ◽  
Dmitri A. Rusakov
Keyword(s):  
Nmda Receptor ◽  
Ampa Receptors ◽  
Monte Carlo Model ◽  
Release Site ◽  
Synaptic Cleft ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Central Synapses ◽  
Prevailing View

The prevailing view at present is that postsynaptic expression of the classical NMDA receptor-dependent long-term potentiation relies on an increase in the numbers of local AMPA receptors (AMPARs). This is thought to parallel an expansion of postsynaptic cell specializations, for instance dendritic spine heads, which accommodate synaptic receptor proteins. However, glutamate released into the synaptic cleft can normally activate only a hotspot of low-affinity AMPARs that occur in the vicinity of the release site. How the enlargement of the AMPAR pool is causally related to the potentiated AMPAR current remains therefore poorly understood. To understand possible scenarios of postsynaptic potentiation, here we explore a detailed Monte Carlo model of the typical small excitatory synapse. Simulations suggest that approximately 50% increase in the synaptic AMPAR current could be provided by expanding the existing AMPAR pool at the expense of 100–200% new AMPARs added at the same packing density. Alternatively, reducing the inter-receptor distances by only 30–35% could achieve a similar level of current potentiation without any changes in the receptor numbers. The NMDA receptor current also appears sensitive to the NMDA receptor crowding. Our observations provide a quantitative framework for understanding the ‘resource-efficient’ ways to enact use-dependent changes in the architecture of central synapses.

scholarly journals GluR2 protein-protein interactions and the regulation of AMPA receptors during synaptic plasticity

2003 ◽  
Vol 358 (1432) ◽  
pp. 715-720 ◽  
Author(s):  
Fabrice Duprat ◽  
Michael Daw ◽  
Wonil Lim ◽  
Graham Collingridge ◽  
John Isaac
Keyword(s):  
Synaptic Plasticity ◽  
Ampa Receptor ◽  
Protein Interactions ◽  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Synaptic Proteins ◽  
Mammalian Brain ◽  
Protein Protein Interactions ◽  
Term Potentiation

AMPA-type glutamate receptors mediate most fast excitatory synaptic transmissions in the mammalian brain. They are critically involved in the expression of long-term potentiation and long-term depression, forms of synaptic plasticity that are thought to underlie learning and memory. A number of synaptic proteins have been identified that interact with the intracellular C-termini of AMPA receptor subunits. Here, we review recent studies and present new experimental data on the roles of these interacting proteins in regulating the AMPA receptor function during basal synaptic transmission and plasticity.

Correlations between immediate early gene induction and the persistence of long-term potentiation

Neuroscience ◽  
1993 ◽  
Vol 56 (3) ◽  
pp. 717-727 ◽  
Author(s):  
W.C. Abraham ◽  
S.E. Mason ◽  
J. Demmer ◽  
J.M. Williams ◽  
C.L. Richardson ◽  
...  
Keyword(s):  
Immediate Early Gene ◽  
Long Term Potentiation ◽  
Gene Induction ◽  
Early Gene ◽  
Immediate Early ◽  
Term Potentiation
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