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 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 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 Electro-acupuncture alleviates motor deficits and maladaptive striatal plasticity in partial-lesioned parkinsonian mice

2020 ◽  
Author(s):  
Wenting Su ◽  
Jianan Yu ◽  
Min Li ◽  
Ke Wang ◽  
Chang Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Synaptic Plasticity ◽  
Nmda Receptors ◽  
Glutamate Receptors ◽  
Motor Skills ◽  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
6 Hydroxydopamine

Abstract Background Parkinson's disease is characterized by abnormal synaptic transmission in the corticostriatal circuit that leads to deficits in motor abilities. Electro-acupuncture has shown to improve the motor behaviors in parkinsonian models. However, the potential mechanisms underlying the electro-acupuncture treatment, specifically in the partial-lesioned model, remain unclear. Methods By utilizing multiple approaches, including electrophysiological, immunohistochemistrical, molecular and behavioral methods, we assessed the effect of electro-acupuncture on the motor dysfunction and striatal synaptic plasticity in a partial-lesioned mouse model induced by intrastriatal injection of 6-hydroxydopamine. Results Electro-acupuncture ameliorated the disrupted gross and fine motor skills in 6-hydroxydopamine-lesioned mice. Notably, electro-acupuncture not only restored the injured corticostriatal long-term potentiation, but also reversed the loss of GluN1-containing NMDA receptors and GluA1-containing AMPA receptors in the striatum. Furthermore, the antagonists selective for AMPA receptors and NMDA receptors blocked the effect of electro-acupuncture on the corticostriatal long-term potentiation in 6-hydroxydopamine-treated mice. Conclusions These data suggest that the postsynaptic glutamate receptors in the striatum undergo the maladaptive changes in the early stage of Parkinson's disease. Electro-acupuncture improves the motor skills via a mechanism involving the modulation of corticostriatal synaptic plasticity and specific glutamate receptors in a partial-lesioned rodent model.

scholarly journals Activity-dependent netrin-1 secretion drives synaptic insertion of GluA1-containing AMPA receptors in the hippocampus

2018 ◽  
Author(s):  
Stephen D. Glasgow ◽  
Simon Labrecque ◽  
Ian V. Beamish ◽  
Sarah Aufmkolk ◽  
Julien Gibon ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Guidance Cue ◽  
Term Potentiation ◽  
Nmdar Activation ◽  
Genetic Deletion ◽  
Adult Hippocampus ◽  
Activity Dependent

AbstractDynamic trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPARs) to synapses is critical for activity-dependent synaptic plasticity underlying learning and memory, however the identity of key molecular effectors remains elusive. Here, we demonstrate that membrane depolarization and N-methyl-D-aspartate receptor (NMDAR) activation triggers secretion of the chemotropic guidance cue netrin-1 from dendrites. Using selective genetic deletion, we show that netrin-1 expression by excitatory neurons is required for NMDAR-dependent long-term potentiation (LTP) in the adult hippocampus. Further, we demonstrate that application of exogenous netrin-1 is sufficient to trigger the potentiation of excitatory glutamatergic transmission at hippocampal Schaffer collateral synapses via Ca2+-dependent recruitment of GluA1-containing AMPARs, promoting the maturation of immature or nascent synapses. These findings identify a central role for activity-dependent release of netrin-1 as a critical effector of synaptic plasticity in the adult hippocampus.

Brivaracetam Prevents the Over-expression of Synaptic Vesicle Protein 2A and Rescues the Deficits of Hippocampal Long-term Potentiation In Vivo in Chronic Temporal Lobe Epilepsy Rats

2020 ◽  
Vol 17 (4) ◽  
pp. 354-360 ◽  
Author(s):  
Yu-Xing Ge ◽  
Ying-Ying Lin ◽  
Qian-Qian Bi ◽  
Yu-Juan Chen
Keyword(s):  
Synaptic Plasticity ◽  
Temporal Lobe Epilepsy ◽  
Synaptic Vesicle ◽  
Long Term Potentiation ◽  
Synaptic Dysfunction ◽  
Over Expression ◽  
Term Potentiation ◽  
Synaptic Vesicle Protein 2A

Background: Patients with temporal lobe epilepsy (TLE) usually suffer from cognitive deficits and recurrent seizures. Brivaracetam (BRV) is a novel anti-epileptic drug (AEDs) recently used for the treatment of partial seizures with or without secondary generalization. Different from other AEDs, BRV has some favorable properties on synaptic plasticity. However, the underlying mechanisms remain elusive. Objective: The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats. Methods: The effect of chronic treatment with BRV (10 mg/kg) was assessed on Pilocarpine induced TLE model through measurement of the field excitatory postsynaptic potentials (fEPSPs) in vivo. Differentially expressed synaptic vesicle protein 2A (SV2A) were identified with immunoblot. Then, fast phosphorylation of synaptosomal-associated protein 25 (SNAP-25) during long-term potentiation (LTP) induction was performed to investigate the potential roles of BRV on synaptic plasticity in the TLE model. Results: An increased level of SV2A accompanied by a depressed LTP in the hippocampus was shown in epileptic rats. Furthermore, BRV treatment continued for more than 30 days improved the over-expression of SV2A and reversed the synaptic dysfunction in epileptic rats. Additionally, BRV treatment alleviates the abnormal SNAP-25 phosphorylation at Ser187 during LTP induction in epileptic ones, which is relevant to the modulation of synaptic vesicles exocytosis and voltagegated calcium channels. Conclusion: BRV treatment ameliorated the over-expression of SV2A in the hippocampus and rescued the synaptic dysfunction in epileptic rats. These results identify the neuroprotective effect of BRV on TLE model.

Prenatal stress in rats attenuates hippocampal long-term potentiation and induces deficits in synaptic plasticity

2006 ◽  
Vol 16 ◽  
pp. S52
Author(s):  
S. Salomon ◽  
Y. Nachum-Biala ◽  
Y. Bogush ◽  
M. Lineal ◽  
H. Matzner ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Prenatal Stress ◽  
Long Term Potentiation ◽  
Term Potentiation

scholarly journals Synaptic plasticity-dependent competition rule influences memory formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yire Jeong ◽  
Hye-Yeon Cho ◽  
Mujun Kim ◽  
Jung-Pyo Oh ◽  
Min Soo Kang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Fear Conditioning ◽  
Long Term Potentiation ◽  
Memory Formation ◽  
Specific Pattern ◽  
Memory Encoding ◽  
Competition Rule ◽  
Term Potentiation ◽  
Input Activity

AbstractMemory is supported by a specific collection of neurons distributed in broad brain areas, an engram. Despite recent advances in identifying an engram, how the engram is created during memory formation remains elusive. To explore the relation between a specific pattern of input activity and memory allocation, here we target a sparse subset of neurons in the auditory cortex and thalamus. The synaptic inputs from these neurons to the lateral amygdala (LA) are not potentiated by fear conditioning. Using an optogenetic priming stimulus, we manipulate these synapses to be potentiated by the learning. In this condition, fear memory is preferentially encoded in the manipulated cell ensembles. This change, however, is abolished with optical long-term depression (LTD) delivered shortly after training. Conversely, delivering optical long-term potentiation (LTP) alone shortly after fear conditioning is sufficient to induce the preferential memory encoding. These results suggest a synaptic plasticity-dependent competition rule underlying memory formation.

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