scholarly journals Mechanism underlying hippocampal long-term potentiation and depression based on competition between endocytosis and exocytosis of AMPA receptors

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tomonari Sumi ◽  
Kouji Harada
Keyword(s):  
Ampa Receptors ◽  
Molecular Motor ◽  
Signal Transmission ◽  
Long Term Potentiation ◽  
Synaptic Membranes ◽  
Recycling Endosome ◽  
Independent Manner ◽  
Term Potentiation ◽  
Ampar Trafficking

Abstract N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) and long-term depression (LTD) of signal transmission form neural circuits and thus are thought to underlie learning and memory. These mechanisms are mediated by AMPA receptor (AMPAR) trafficking in postsynaptic neurons. However, the regulatory mechanism of bidirectional plasticity at excitatory synapses remains unclear. We present a network model of AMPAR trafficking for adult hippocampal pyramidal neurons, which reproduces both LTP and LTD. We show that the induction of both LTP and LTD is regulated by the competition between exocytosis and endocytosis of AMPARs, which are mediated by the calcium-sensors synaptotagmin 1/7 (Syt1/7) and protein interacting with C-kinase 1 (PICK1), respectively. Our result indicates that recycling endosomes containing AMPAR are always ready for Syt1/7-dependent exocytosis of AMPAR at peri-synaptic/synaptic membranes. This is because molecular motor myosin Vb constitutively transports the recycling endosome toward the membrane in a Ca2+-independent manner.

scholarly journals A Multisubcellular Compartment Model of AMPA Receptor Trafficking for Neuromodulation of Hebbian Synaptic Plasticity

2021 ◽  
Vol 13 ◽  
Author(s):  
Stefan Mihalas ◽  
Alvaro Ardiles ◽  
Kaiwen He ◽  
Adrian Palacios ◽  
Alfredo Kirkwood
Keyword(s):  
Synaptic Plasticity ◽  
Ampa Receptors ◽  
Compartment Model ◽  
Long Term Potentiation ◽  
Reverse Direction ◽  
Term Potentiation ◽  
Simple Kinetic Model ◽  
Ampar Trafficking ◽  
Central Synapses

Neuromodulation can profoundly impact the gain and polarity of postsynaptic changes in Hebbian synaptic plasticity. An emerging pattern observed in multiple central synapses is a pull–push type of control in which activation of receptors coupled to the G-protein Gs promote long-term potentiation (LTP) at the expense of long-term depression (LTD), whereas receptors coupled to Gq promote LTD at the expense of LTP. Notably, coactivation of both Gs- and Gq-coupled receptors enhances the gain of both LTP and LTD. To account for these observations, we propose a simple kinetic model in which AMPA receptors (AMPARs) are trafficked between multiple subcompartments in and around the postsynaptic spine. In the model AMPARs in the postsynaptic density compartment (PSD) are the primary contributors to synaptic conductance. During LTP induction, AMPARs are trafficked to the PSD primarily from a relatively small perisynaptic (peri-PSD) compartment. Gs-coupled receptors promote LTP by replenishing peri-PSD through increased AMPAR exocytosis from a pool of endocytic AMPAR. During LTD induction AMPARs are trafficked in the reverse direction, from the PSD to the peri-PSD compartment, and Gq-coupled receptors promote LTD by clearing the peri-PSD compartment through increased AMPAR endocytosis. We claim that the model not only captures essential features of the pull–push neuromodulation of synaptic plasticity, but it is also consistent with other actions of neuromodulators observed in slice experiments and is compatible with the current understanding of AMPAR trafficking.

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 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.

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.

scholarly journals The AMPA receptor-associated protein Shisa7 regulates hippocampal synaptic function and contextual memory

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Leanne J M Schmitz ◽  
Remco V Klaassen ◽  
Marta Ruiperez-Alonso ◽  
Azra Elia Zamri ◽  
Jasper Stroeder ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Fear Memory ◽  
Synaptic Function ◽  
Glutamatergic Synapses ◽  
Contextual Fear ◽  
Receptor Associated Protein ◽  
Term Potentiation ◽  
Bona Fide

Glutamatergic synapses rely on AMPA receptors (AMPARs) for fast synaptic transmission and plasticity. AMPAR auxiliary proteins regulate receptor trafficking, and modulate receptor mobility and its biophysical properties. The AMPAR auxiliary protein Shisa7 (CKAMP59) has been shown to interact with AMPARs in artificial expression systems, but it is unknown whether Shisa7 has a functional role in glutamatergic synapses. We show that Shisa7 physically interacts with synaptic AMPARs in mouse hippocampus. Shisa7 gene deletion resulted in faster AMPAR currents in CA1 synapses, without affecting its synaptic expression. Shisa7 KO mice showed reduced initiation and maintenance of long-term potentiation of glutamatergic synapses. In line with this, Shisa7 KO mice showed a specific deficit in contextual fear memory, both short-term and long-term after conditioning, whereas auditory fear memory and anxiety-related behavior were normal. Thus, Shisa7 is a bona-fide AMPAR modulatory protein affecting channel kinetics of AMPARs, necessary for synaptic hippocampal plasticity, and memory recall.

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