Faculty Opinions recommendation of Activity-Dependent Netrin-1 Secretion Drives Synaptic Insertion of GluA1-Containing AMPA Receptors in the Hippocampus.

2018 ◽  
Author(s):  
Johannes Hell
Keyword(s):  
Ampa Receptors ◽  
Activity Dependent

scholarly journals GluA4 subunit of AMPA receptors mediates the early synaptic response to altered network activity in the developing hippocampus

2016 ◽  
Vol 115 (6) ◽  
pp. 2989-2996 ◽  
Author(s):  
J. Huupponen ◽  
T. Atanasova ◽  
T. Taira ◽  
S. E. Lauri
Keyword(s):  
Ampa Receptors ◽  
Pyramidal Neurons ◽  
Activity Patterns ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Postnatal Period ◽  
Homeostatic Plasticity ◽  
Network Activity ◽  
Hippocampal Pyramidal Neurons ◽  
Activity Dependent

Development of the neuronal circuitry involves both Hebbian and homeostatic plasticity mechanisms that orchestrate activity-dependent refinement of the synaptic connectivity. AMPA receptor subunit GluA4 is expressed in hippocampal pyramidal neurons during early postnatal period and is critical for neonatal long-term potentiation; however, its role in homeostatic plasticity is unknown. Here we show that GluA4-dependent plasticity mechanisms allow immature synapses to promptly respond to alterations in network activity. In the neonatal CA3, the threshold for homeostatic plasticity is low, and a 15-h activity blockage with tetrodotoxin triggers homeostatic upregulation of glutamatergic transmission. On the other hand, attenuation of the correlated high-frequency bursting in the CA3-CA1 circuitry leads to weakening of AMPA transmission in CA1, thus reflecting a critical role for Hebbian synapse induction in the developing CA3-CA1. Both of these developmentally restricted forms of plasticity were absent in GluA4 −/− mice. These data suggest that GluA4 enables efficient homeostatic upscaling and responsiveness to temporal activity patterns during the critical period of activity-dependent refinement of the circuitry.

scholarly journals Development of an Activity Dependent, Photochemically-Released Tool for the Study of Calcium Permeable AMPA Receptors

2013 ◽  
Vol 104 (2) ◽  
pp. 499a
Author(s):  
Amanda M. Hussey ◽  
Rosamund E. Combs-Bachmann ◽  
Devaiah Vytla ◽  
Ismail Hafez ◽  
James J. Chambers
Keyword(s):  
Ampa Receptors ◽  
Activity Dependent

scholarly journals Synaptic Activity-Dependent Changes in the Hippocampal Palmitoylome

2021 ◽  
Author(s):  
Glory Nasseri ◽  
Nusrat Matin ◽  
Kira Tosefsky ◽  
Richard Greg Stacey ◽  
Stephane Flibotte ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Ampa Receptors ◽  
Protein S ◽  
Postsynaptic Membrane ◽  
Synaptic Activity ◽  
Synaptic Proteins ◽  
Full Characterization ◽  
Metabolic Functions ◽  
Synapse Plasticity ◽  
Activity Dependent

Dynamic protein S-palmitoylation is critical for neuronal function, development, and synaptic plasticity. Activity-dependent changes in palmitoylation have been observed for several neuronal substrates, however a full characterization of the activity-regulated palmitoylome is lacking. Here, we use an unbiased approach to identify differentially palmitoylated proteins in the mouse hippocampus following context-dependent fear conditioning. Of the 121 differentially palmitoylated proteins identified 63 were synaptic proteins, while others were associated with metabolic functions, cytoskeletal organization, and signal transduction. The vast majority of synaptic proteins exhibited increased palmitoylation following fear conditioning, whereas proteins that exhibited decreased palmitoylation were predominantly associated with metabolic processes. We show a link between dynamic palmitoylation and synapse plasticity by demonstrating that the palmitoylation of one of our identified proteins, PRG-1/LPPR4, is essential for activity-induced insertion of AMPA receptors into the postsynaptic membrane. Together, this study identifies networks of synaptic proteins whose dynamic palmitoylation may play a central role in learning and memory.

scholarly journals Activity-dependent synaptic GRIP1 accumulation drives synaptic scaling up in response to action potential blockade

2015 ◽  
Vol 112 (27) ◽  
pp. E3590-E3599 ◽  
Author(s):  
Melanie A. Gainey ◽  
Vedakumar Tatavarty ◽  
Marc Nahmani ◽  
Heather Lin ◽  
Gina G. Turrigiano
Keyword(s):  
Action Potential ◽  
Ampa Receptors ◽  
Scaling Up ◽  
Receptor Trafficking ◽  
Neuronal Firing ◽  
Homeostatic Plasticity ◽  
Synaptic Scaling ◽  
Interacting Protein ◽  
Excitatory Postsynaptic Currents ◽  
Activity Dependent

Synaptic scaling is a form of homeostatic plasticity that stabilizes neuronal firing in response to changes in synapse number and strength. Scaling up in response to action-potential blockade is accomplished through increased synaptic accumulation of GluA2-containing AMPA receptors (AMPAR), but the receptor trafficking steps that drive this process remain largely obscure. Here, we show that the AMPAR-binding protein glutamate receptor-interacting protein-1 (GRIP1) is essential for regulated synaptic AMPAR accumulation during scaling up. Synaptic abundance of GRIP1 was enhanced by activity deprivation, directly increasing synaptic GRIP1 abundance through overexpression increased the amplitude of AMPA miniature excitatory postsynaptic currents (mEPSCs), and shRNA-mediated GRIP1 knockdown prevented scaling up of AMPA mEPSCs. Furthermore, knockdown and replace experiments targeting either GRIP1 or GluA2 revealed that scaling up requires the interaction between GRIP1 and GluA2. Finally, GRIP1 synaptic accumulation during scaling up did not require GluA2 binding. Taken together, our data support a model in which activity-dependent trafficking of GRIP1 to synaptic sites drives the forward trafficking and enhanced synaptic accumulation of GluA2-containing AMPAR during synaptic scaling up.

scholarly journals PICK1 regulates AMPA receptor endocytosis via direct interactions with AP2 α-appendage and dynamin

2017 ◽  
Vol 216 (10) ◽  
pp. 3323-3338 ◽  
Author(s):  
Maria Fiuza ◽  
Christine M. Rostosky ◽  
Gabrielle T. Parkinson ◽  
Alexei M. Bygrave ◽  
Nagaraj Halemani ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Molecular Mechanisms ◽  
Diverse Range ◽  
Bar Domain ◽  
Receptor Endocytosis ◽  
The Core ◽  
Cargo Proteins ◽  
Nmdar Activation ◽  
Activity Dependent

Clathrin-mediated endocytosis (CME) is used to internalize a diverse range of cargo proteins from the cell surface, often in response to specific signals. In neurons, the rapid endocytosis of GluA2-containing AMPA receptors (AMPARs) in response to NMDA receptor (NMDAR) stimulation causes a reduction in synaptic strength and is the central mechanism for long-term depression, which underlies certain forms of learning. The mechanisms that link NMDAR activation to CME of AMPARs remain elusive. PICK1 is a BAR domain protein required for NMDAR-dependent reductions in surface GluA2; however, the molecular mechanisms involved are unclear. In this study, we show that PICK1 makes direct, NMDAR-dependent interactions with the core endocytic proteins AP2 and dynamin. PICK1–AP2 interactions are required for clustering AMPARs at endocytic zones in dendrites in response to NMDAR stimulation and for consequent AMPAR internalization. We further show that PICK1 stimulates dynamin polymerization. We propose that PICK1 is a cargo-specific endocytic accessory protein required for efficient, activity-dependent AMPAR endocytosis.

Postsynaptic Mechanisms Are Essential for Forskolin-Induced Potentiation of Synaptic Transmission

2006 ◽  
Vol 95 (4) ◽  
pp. 2570-2579 ◽  
Author(s):  
Irina V. Sokolova ◽  
Henry A. Lester ◽  
Norman Davidson
Keyword(s):  
Synaptic Transmission ◽  
Ampa Receptors ◽  
Internal Solution ◽  
Whole Cell ◽  
Perforated Patch ◽  
Cell Configuration ◽  
Nmda Receptor Blockade ◽  
Mepsc Frequency ◽  
Pka Pathway ◽  
Activity Dependent

It has been demonstrated that stimulation of protein kinase A (PKA) results in enhanced synaptic transmission in the hippocampus and other brain areas. To investigate mechanisms of the PKA-mediated potentiation of synaptic transmission, we used rat hippocampal embryonic cultures. In low-density cultures, paired recordings under the perforated patch demonstrated that 15-min forskolin treatment produced long-lasting potentiation of evoked excitatory postsynaptic currents (eEPSCs) mediated by the cAMP/PKA pathway. eEPSC amplitudes increased to 240 ± 10% of baseline after 15 min of forskolin treatment (early). After forskolin washout, eEPSCs declined to a potentiated level. Potentiation was sustained for ≥85 min after forskolin washout and, 60 min after forskolin washout, constituted 152 ± 7% of baseline (late potentiation). Disruption of presynaptic processes with the whole cell configuration and internal solution containing PKA inhibitor peptide did not affect forskolin-induced potentiation. Disruption of postsynaptic processes, in contrast, impaired early potentiation and abolished late potentiation. Study of mEPSCs confirmed the contribution of postsynaptic mechanisms. Forskolin-induced enhancement of mEPSC frequency observed under the perforated patch was attenuated by the whole cell configuration. Forskolin also induced an increase of mEPSC amplitudes in the perforated patch, but not in the whole cell, experiments. Potentiation of eEPSCs was not activity dependent, persisting in the absence of stimulation. NMDA receptor blockade did not abolish forskolin-induced potentiation. In summary, we demonstrate that forskolin-induced potentiation of eEPSCs was mediated by postsynaptic mechanisms, presumably by upregulation of AMPA receptors by phosphorylation.

Regulation of actin cytoskeleton is involved in activity-dependent traffickings of AMPA-receptors in cerebellar Purkinje cell

2007 ◽  
Vol 58 ◽  
pp. S52
Author(s):  
Kazuhiko Yamaguchi ◽  
Tetsuya Tatsukawa ◽  
Hiroshi Todaka ◽  
Dharmaraj Elakkat ◽  
Soichi Nagao ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Purkinje Cell ◽  
Ampa Receptors ◽  
Cerebellar Purkinje Cell ◽  
Activity Dependent ◽  
Regulation Of Actin Cytoskeleton

scholarly journals PDZ protein mediated activity-dependent LTP/LTD developmental switch at rat retinocollicular synapses

2010 ◽  
Vol 298 (6) ◽  
pp. C1572-C1582 ◽  
Author(s):  
Lei Xue ◽  
Fan Zhang ◽  
Xianhua Chen ◽  
Junji Lin ◽  
Jian Shi
Keyword(s):  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Basic Mechanism ◽  
Long Term Effects ◽  
Interacting Protein ◽  
Term Potentiation ◽  
Retinal Input ◽  
Pdz Protein ◽  
Activity Dependent

The insertion of amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors into the plasma membrane and removal via internalization are essential for regulating synaptic strength, which underlies the basic mechanism of learning and memory. The retinocollicular pathway undergoes synaptic refinement during development and shows a wide variety of long-term synaptic changes; however, still little is known about its underlying molecular regulation. Here we report a rapid developmental long-term potentiation (LTP)/long-term depression (LTD) switch and its intracellular mechanism at the rat retinocollicular pathway from postnatal day 5 (P5) to P14. Before P9, neurons always exhibited LTP, whereas LTD was observed only after P10. Blockade of GluR2/3-glutamate receptor-interacting protein (GRIP)/AMPA-receptor-binding protein (ABP)/protein interacting with C kinase 1 (PICK1) interactions with pep2-SVKI could sustain the LTP after P10. This suggests that the LTP/LTD switch relied on PDZ protein activities. Selective interruption of GluR2/3-PICK1 binding by pep2-EVKI blocked the long-lasting effects of both LTP and LTD, suggesting a role for PICK1 in the maintenance of long-term synaptic plasticity. Interestingly, synaptic expression of GRIP increased more than twofold from P7 to P11, whereas ABP and PICK1 expression levels remained stable. Blockade of spontaneous retinal input suppressed this increase and abolished the LTP/LTD switch. These results suggest that the increased GRIP synaptic expression may be a key regulatory factor in mediating the activity-dependent developmental LTP/LTD switch, whereas PICK1 may be required for both LTP and LTD to maintain their long-term effects.

scholarly journals SUSD4 Controls Activity-Dependent Degradation of AMPA Receptor GLUA2 and Synaptic Plasticity

2019 ◽  
Author(s):  
I. González-Calvo ◽  
K. Iyer ◽  
M. Carquin ◽  
A. Khayachi ◽  
F.A. Giuliani ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Motor Coordination ◽  
Transmembrane Protein ◽  
Ubiquitin Ligases ◽  
Potential Contribution ◽  
Dependent Manner ◽  
Activity Dependent

SummaryAt excitatory synapses, the choice between recycling or degradation of glutamate AMPA receptors controls the direction of synaptic plasticity. In this context, how the degradation machinery is targeted to specific synaptic substrates in an activity-dependent manner is not understood. Here we show that SUSD4, a complement-related transmembrane protein, is a tether for HECT ubiquitin ligases of the NEDD4 subfamily, which promote the degradation of a large number of cellular substrates. SUSD4 is expressed by many neuronal populations starting at the time of synapse formation. Loss-of-function of Susd4 in the mouse prevents activity-dependent degradation of the GLUA2 AMPA receptor subunit and long-term depression at cerebellar synapses, and leads to impairment in motor coordination adaptation and learning. SUSD4 could thus act as an adaptor targeting NEDD4 ubiquitin ligases to AMPA receptors during long-term synaptic plasticity. These findings shed light on the potential contribution of SUSD4 mutations to the etiology of neurodevelopmental diseases.

Sign in / Sign up

Export Citation Format

Share Document