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https://www.readbyqxmd.com/read/30545844/synaptotagmin-3-drives-ampa-receptor-endocytosis-depression-of-synapse-strength-and-forgetting
#1
Ankit Awasthi, Binu Ramachandran, Saheeb Ahmed, Eva Benito, Yo Shinoda, Noam Nitzan, Alina Heukamp, Sabine Rannio, Henrik Martens, Jonas Barth, Katja Burk, Yu Tian Wang, Andre Fischer, Camin Dean
Forgetting is important. Without it, the relative importance of acquired memories in a changing environment is lost. We discovered that Synaptotagmin-3 (Syt3) localizes to post-synaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation. AMPA receptor internalization, long-term-depression (LTD), and decay of long-term-potentiation (LTP) of synaptic strength required calcium-sensing by Syt3, and were abolished by Syt3 knockout. In spatial memory tasks Syt3 knockout mice learned normally, but exhibited a lack of forgetting...
December 13, 2018: Science
https://www.readbyqxmd.com/read/30537817/phosphorylation-induces-conformational-rigidity-at-the-c-terminal-domain-of-ampa-%C3%AE-amino-3-hydroxy-5-methyl-4-isoxazolepropionic-acid-receptors
#2
Sudeshna Chatterjee, Carina Ade, Caitlin Edmunds Nurik, Nicole C Carrejo, Chayan Dutta, Vasanthi Jayaraman, Christy F Landes
The intracellular C-terminal domain (CTD) of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor undergoes phosphorylation at specific locations during long-term potentiation (LTP). This modification enhances conductance through the AMPA receptor ion channel and thus potentially plays a crucial role in modulating receptor trafficking and signaling. However, because the CTD structure is largely unresolved, it is difficult to establish if phosphorylation induces conformational changes that might play a role in enhancing channel conductance...
December 11, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/30524263/the-role-of-calcium-permeable-ampars-in-long-term-potentiation-at-principal-neurons-in-the-rodent-hippocampus
#3
REVIEW
Pojeong Park, Heather Kang, Thomas M Sanderson, Zuner A Bortolotto, John Georgiou, Min Zhuo, Bong-Kiun Kaang, Graham L Collingridge
Long-term potentiation (LTP) at hippocampal CA1 synapses is classically triggered by the synaptic activation of NMDA receptors (NMDARs). More recently, it has been shown that calcium-permeable (CP) AMPA receptors (AMPARs) can also trigger synaptic plasticity at these synapses. Here, we review this literature with a focus on recent evidence that CP-AMPARs are critical for the induction of the protein kinase A (PKA)- and protein synthesis-dependent component of LTP.
2018: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/30508566/developmental-perfluorooctane-sulfonate-exposure-inhibits-long-term-potentiation-by-affecting-ampa-receptor-trafficking
#4
Qian Zhang, Wei Liu, Huimin Zhao, Zhou Zhang, Hui Qin, Fang Luo, Qiao Niu
Both animal study and epidemiological survey revealed the associations between defects of cognitive function and the developmental exposure to perfluorooctane sulfonate (PFOS), while the mechanism is not well known. The SD rats were exposed PFOS at 1.7, 5 and 15 mg/L by drinking water from gestation to the adulthood of the pups for evaluating the effects of PFOS exposure on long-term potentiation (LTP) and the role of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors trafficking. Whole-life exposure of PFOS beginning in utero to adulthood significantly inhibited the induction and expression of LTP, and the input/output curve (I/O) and paired-pulse facilitation (PPF) were moderately suppressed, suggesting that PFOS might affect the synaptic transmission and plasticity both in pre- and post-synaptic cells...
November 30, 2018: Toxicology
https://www.readbyqxmd.com/read/30485550/cognitive-deficits-in-mice-lacking-nsun5-a-cytosine-5-rna-methyltransferase-with-impairment-of-oligodendrocyte-precursor-cells
#5
Tingting Zhang, Peipei Chen, Wei Li, Sha Sha, Ya Wang, Zihao Yuan, Bin Shen, Ling Chen
Williams-Beuren syndrome (WBS) is a microdeletion disorder with cognitive phenotype. NSUN5 gene, which encodes a cytosine-5 RNA methyltransferase, is located in WBS deletion locus. To investigate the influence of NSUN5 deletion on cognitive behaviors, we produced single-gene Nsun5 knockout (Nsun5-KO) mice. Here, we report that adult Nsun5-KO mice showed spatial cognitive deficits. Size of the brain and hippocampal structures and the number of CA1 or CA3 pyramidal cells in Nsun5-KO mice did not differ from WT mice...
November 28, 2018: Glia
https://www.readbyqxmd.com/read/30425622/mechanisms-and-role-of-dendritic-membrane-trafficking-for-long-term-potentiation
#6
Brian G Hiester, Matthew I Becker, Aaron B Bowen, Samantha L Schwartz, Matthew J Kennedy
Long-term potentiation (LTP) of excitatory synapses is a major form of plasticity for learning and memory in the central nervous system. While the molecular mechanisms of LTP have been debated for decades, there is consensus that LTP induction activates membrane trafficking pathways within dendrites that are essential for synapse growth and strengthening. Current models suggest that key molecules for synaptic potentiation are sequestered within intracellular organelles, which are mobilized by synaptic activity to fuse with the plasma membrane following LTP induction...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/30415706/silent-learning
#7
Janine I Rossato, Andrea Moreno, Lisa Genzel, Miwako Yamasaki, Tomonori Takeuchi, Santiago Canals, Richard G M Morris
We introduce the concept of "silent learning"-the capacity to learn despite neuronal cell-firing being largely absent. This idea emerged from thinking about dendritic computation [1, 2] and examining whether the encoding, expression, and retrieval of hippocampal-dependent memory could be dissociated using the intrahippocampal infusion of pharmacological compounds. We observed that very modest enhancement of GABAergic inhibition with low-dose muscimol blocked both cell-firing and the retrieval of an already-formed memory but left induction of long-term potentiation (LTP) and new spatial memory encoding intact (silent learning)...
November 5, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/30365266/-progress-of-researches-on-mechanisms-of-acupuncture-therapy-in-regulating-brain-plasticity
#8
Zhong-Ren Sun, Xiao-Lin Lü, Hong-Na Yin, Ji-Shun Hao, Xiang-Xin Zeng, Zhu-Xin Li
Brain plasticity is referred to the ability of the brain to change in structure and functional activities from microscopic aspects (synapses) in individual neurons to larger-scale aspects such as cortical remapping, neuronal remodeling, etc. in response to injury. Acupuncture has a positive effect in the treatment of cerebral diseases, thus leading to an increasing research on its underlying mechanisms in regulating brain plasticity. The present paper reviewed recent development of studies on acupuncture treatment of Alzheimer's disease, vascular dementia, cerebral ischemia, bone cancer pain, autism, etc...
October 25, 2018: Zhen Ci Yan Jiu, Acupuncture Research
https://www.readbyqxmd.com/read/30364291/ampa-receptor-trafficking-for-postsynaptic-potentiation
#9
REVIEW
Mikyoung Park
Long-term potentiation (LTP) of excitatory synaptic strength, which has long been considered a synaptic correlate for learning and memory, requires a fast recruitment of additional α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors (AMPARs) to the postsynaptic sites. As cell biological concepts have been applied to the field and genetic manipulation and microscopic imaging technologies have been advanced, visualization of the trafficking of AMPARs to synapses for LTP has been investigated intensively over the last decade...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/30359599/the-ampa-receptor-code-of-synaptic-plasticity
#10
REVIEW
Graham H Diering, Richard L Huganir
Changes in the properties and postsynaptic abundance of AMPA-type glutamate receptors (AMPARs) are major mechanisms underlying various forms of synaptic plasticity, including long-term potentiation (LTP), long-term depression (LTD), and homeostatic scaling. The function and the trafficking of AMPARs to and from synapses is modulated by specific AMPAR GluA1-GluA4 subunits, subunit-specific protein interactors, auxiliary subunits, and posttranslational modifications. Layers of regulation are added to AMPAR tetramers through these different interactions and modifications, increasing the computational power of synapses...
October 24, 2018: Neuron
https://www.readbyqxmd.com/read/30355502/akap150-palmitoylation-regulates-synaptic-incorporation-of-ca-2-permeable-ampa-receptors-to-control-ltp
#11
Alicia M Purkey, Kevin M Woolfrey, Kevin C Crosby, Dominik G Stich, Wallace S Chick, Jason Aoto, Mark L Dell'Acqua
Ca2+ -permeable AMPA-type glutamate receptors (CP-AMPARs) containing GluA1 but lacking GluA2 subunits contribute to multiple forms of synaptic plasticity, including long-term potentiation (LTP), but mechanisms regulating CP-AMPARs are poorly understood. A-kinase anchoring protein (AKAP) 150 scaffolds kinases and phosphatases to regulate GluA1 phosphorylation and trafficking, and trafficking of AKAP150 itself is modulated by palmitoylation on two Cys residues. Here, we developed a palmitoylation-deficient knockin mouse to show that AKAP150 palmitoylation regulates CP-AMPAR incorporation at hippocampal synapses...
October 23, 2018: Cell Reports
https://www.readbyqxmd.com/read/30341179/synaptotoxicity-in-alzheimer-s-disease-involved-a-dysregulation-of-actin-cytoskeleton-dynamics-through-cofilin-1-phosphorylation
#12
Travis Rush, Jose Martinez-Hernandez, Marc Dollmeyer, Marie Lise Frandemiche, Eve Borel, Sylvie Boisseau, Muriel Jacquier-Sarlin, Alain Buisson
Amyloid-β (Aβ) drives the synaptic impairment and dendritic spine loss characteristic of Alzheimer's disease (AD), but how Aβ affects the actin cytoskeleton remains unknown and contentious. The actin-binding protein, cofilin-1 (cof1), is a major regulator of actin dynamics in dendritic spines, and is subject to phospho-regulation by multiple pathways, including the Rho-associated protein kinase (ROCK) pathway. While cof1 is implicated as a driver of the synaptotoxicity characteristic of the early phases of AD pathophysiology, questions remain about the molecular mechanisms involved...
October 19, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/30323233/modulation-of-ampa-receptor-surface-diffusion-restores-hippocampal-plasticity-and-memory-in-huntington-s-disease-models
#13
Hongyu Zhang, Chunlei Zhang, Jean Vincent, Diana Zala, Caroline Benstaali, Matthieu Sainlos, Dolors Grillo-Bosch, Sophie Daburon, Françoise Coussen, Yoon Cho, Denis J David, Frederic Saudou, Yann Humeau, Daniel Choquet
Impaired hippocampal synaptic plasticity contributes to cognitive impairment in Huntington's disease (HD). However, the molecular basis of such synaptic plasticity defects is not fully understood. Combining live-cell nanoparticle tracking and super-resolution imaging, we show that AMPAR surface diffusion, a key player in synaptic plasticity, is disturbed in various rodent models of HD. We demonstrate that defects in the brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling pathway contribute to the deregulated AMPAR trafficking by reducing the interaction between transmembrane AMPA receptor regulatory proteins (TARPs) and the PDZ-domain scaffold protein PSD95...
October 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/30297624/phosphorylation-of-the-ampar-tarp-complex-in-synaptic-plasticity
#14
REVIEW
Joongkyu Park
Synaptic plasticity has been considered a key mechanism underlying many brain functions including learning, memory, and drug addiction. An increase or decrease in synaptic activity of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) complex mediates the phenomena as shown in the cellular models of synaptic plasticity, long-term potentiation (LTP), and depression (LTD). In particular, protein phosphorylation shares the spotlight in expressing the synaptic plasticity. This review summarizes the studies on phosphorylation of the AMPAR pore-forming subunits and auxiliary proteins including transmembrane AMPA receptor regulatory proteins (TARPs) and discusses its role in synaptic plasticity...
October 8, 2018: Proteomes
https://www.readbyqxmd.com/read/30282026/activity-dependent-netrin-1-secretion-drives-synaptic-insertion-of-glua1-containing-ampa-receptors-in-the-hippocampus
#15
Stephen D Glasgow, Simon Labrecque, Ian V Beamish, Sarah Aufmkolk, Julien Gibon, Dong Han, Stephanie N Harris, Paul Dufresne, Paul W Wiseman, R Anne McKinney, Philippe Séguéla, Paul De Koninck, Edward S Ruthazer, Timothy E Kennedy
Dynamic 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, but 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...
October 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/30273629/fluoride-activates-microglia-secretes-inflammatory-factors-and-influences-synaptic-neuron-plasticity-in-the-hippocampus-of-rats
#16
Li Yang, Peiyu Jin, Xiaoyan Wang, Qing Zhou, Xiaoli Lin, Shuhua Xi
Epidemiological studies have reported that highly fluoridated drinking water may significantly decrease the Intelligence Quotient (IQ) of exposed children. It is thought that synaptic plasticity is the basis of learning and memory skills in developing children. However, the effect on synaptic plasticity by activated microglia induced via fluoride treatment is less clear. Our previous research showed that fluoride ions activated microglia which then released pro-inflammatory cytokines. In this study, hippocampal-dependent memory status was evaluated in rat models sub-chronically exposed to fluoride in their drinking water...
September 28, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/30266896/a-unique-intracellular-tyrosine-in-neuroligin-1-regulates-ampa-receptor-recruitment-during-synapse-differentiation-and-potentiation
#17
Mathieu Letellier, Zsófia Szíber, Ingrid Chamma, Camille Saphy, Ioanna Papasideri, Béatrice Tessier, Matthieu Sainlos, Katalin Czöndör, Olivier Thoumine
To better understand the molecular mechanisms by which early neuronal connections mature into synapses, we examined the impact of neuroligin-1 (Nlg1) phosphorylation on synapse differentiation, focusing on a unique intracellular tyrosine (Y782), which differentially regulates Nlg1 binding to PSD-95 and gephyrin. By expressing Nlg1 point mutants (Y782A/F) in hippocampal neurons, we show using imaging and electrophysiology that Y782 modulates the recruitment of functional AMPA receptors (AMPARs). Nlg1-Y782F impaired both dendritic spine formation and AMPAR diffusional trapping, but not NMDA receptor recruitment, revealing the assembly of silent synapses...
September 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/30266286/ultra-micronized-palmitoylethanolamide-rescues-the-cognitive-decline-associated-loss-of-neural-plasticity-in-the-neuropathic-mouse-entorhinal-cortex-dentate-gyrus-pathway
#18
Serena Boccella, Claudia Cristiano, Rosaria Romano, Monica Iannotta, Carmela Belardo, Antonio Farina, Francesca Guida, Fabiana Piscitelli, Enza Palazzo, Mariacristina Mazzitelli, Roberta Imperatore, Lea Tunisi, Vito de Novellis, Luigia Cristino, Vincenzo Di Marzo, Antonio Calignano, Sabatino Maione, Livio Luongo
Chronic pain is associated with cognitive deficits. Palmitoylethanolamide (PEA) has been shown to ameliorate pain and pain-related cognitive impairments by restoring glutamatergic synapses functioning in the spared nerve injury (SNI) of the sciatic nerve in mice. SNI reduced mechanical and thermal threshold, spatial memory and LTP at the lateral entorhinal cortex (LEC)-dentate gyrus (DG) pathway. It decreased also postsynaptic density, volume and dendrite arborization of DG and increased the expression of metabotropic glutamate receptor 1 and 7 (mGluR1 and mGluR7), of the GluR1, GluR1s845 and GluR1s831 subunits of AMPA receptor and the levels of glutamate in the DG...
September 25, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/30243909/apkc-mediated-persistent-increase-in-ampa-nmda-ratio-in-the-vta-participates-in-the-neuroadaptive-signal-necessary-to-induce-nac-synaptic-plasticity-after-cocaine-administration
#19
Ana Del C Vaquer-Alicea, Rafael Vázquez-Torres, Marcos Devarie-Hornedo, Juan C Vicenty-Padilla, Bermary Santos-Vera, Cristina María-Ríos, Maria E Vélez-Hernández, Todd Sacktor, Carlos A Jiménez-Rivera
Chronic cocaine exposure produces enduring neuroadaptations in the brain's reward system. Persistence of early cocaine-evoked neuroadaptations in the ventral tegmental area (VTA) is necessary for later synaptic alterations in the nucleus accumbens (NAc), suggesting a temporal sequence of neuroplastic changes between these two areas. However, the molecular nature of the signal that mediates this sequential event is unknown. Here we used the behavioral sensitization model and the aPKC inhibitor of late-phase LTP maintenance, ZIP, to investigate if a persistent increase in AMPA/NMDA ratio plays a role in the molecular mechanism that allows VTA neuroadaptations to induce changes in the NAc...
November 10, 2018: Neuroscience
https://www.readbyqxmd.com/read/30175650/noradrenergic-gating-of-long-lasting-synaptic-potentiation-in-the-hippocampus-from-neurobiology-to-translational-biomedicine
#20
Peter V Nguyen, Jennifer N Gelinas
Altered synaptic strength underlies information storage in neural circuits. Neuromodulatory transmitters such as norepinephrine (NE) facilitate long-lasting synaptic plasticity by recruiting and modifying multiple molecular elements of synaptic signaling, including specific transmitter receptors, intracellular protein kinases, and translation initiation. NE regulates multiple brain functions such as attention, perception, arousal, sleep, learning, and memory. The mammalian hippocampus receives noradrenergic innervation and hippocampal neurons express β-adrenergic receptors (β-ARs), which bind NE and are critical for gating the induction of long-lasting forms of synaptic potentiation...
September 3, 2018: Journal of Neurogenetics
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