scholarly journals Regulation of AMPA receptor channels and synaptic plasticity by cofilin phosphatase Slingshot in cortical neurons

2010 ◽  
Vol 588 (13) ◽  
pp. 2361-2371 ◽  
Author(s):  
Eunice Y. Yuen ◽  
Wenhua Liu ◽  
Tal Kafri ◽  
Henriette Van Praag ◽  
Zhen Yan
Keyword(s):  
Synaptic Plasticity ◽  
Ampa Receptor ◽  
Cortical Neurons ◽  
Ampa Receptor Channels

scholarly journals Altered network properties in C9ORF72 repeat expansion cortical neurons are due to synaptic dysfunction

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Emma M. Perkins ◽  
Karen Burr ◽  
Poulomi Banerjee ◽  
Arpan R. Mehta ◽  
Owen Dando ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Vesicle ◽  
Cortical Neurons ◽  
Electrode Array ◽  
Repeat Expansion ◽  
Cortical Network ◽  
Synaptic Function ◽  
Network Activity ◽  
Cortical Function ◽  
Network Function

Abstract Background Physiological disturbances in cortical network excitability and plasticity are established and widespread in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients, including those harbouring the C9ORF72 repeat expansion (C9ORF72RE) mutation – the most common genetic impairment causal to ALS and FTD. Noting that perturbations in cortical function are evidenced pre-symptomatically, and that the cortex is associated with widespread pathology, cortical dysfunction is thought to be an early driver of neurodegenerative disease progression. However, our understanding of how altered network function manifests at the cellular and molecular level is not clear. Methods To address this we have generated cortical neurons from patient-derived iPSCs harbouring C9ORF72RE mutations, as well as from their isogenic expansion-corrected controls. We have established a model of network activity in these neurons using multi-electrode array electrophysiology. We have then mechanistically examined the physiological processes underpinning network dysfunction using a combination of patch-clamp electrophysiology, immunocytochemistry, pharmacology and transcriptomic profiling. Results We find that C9ORF72RE causes elevated network burst activity, associated with enhanced synaptic input, yet lower burst duration, attributable to impaired pre-synaptic vesicle dynamics. We also show that the C9ORF72RE is associated with impaired synaptic plasticity. Moreover, RNA-seq analysis revealed dysregulated molecular pathways impacting on synaptic function. All molecular, cellular and network deficits are rescued by CRISPR/Cas9 correction of C9ORF72RE. Our study provides a mechanistic view of the early dysregulated processes that underpin cortical network dysfunction in ALS-FTD. Conclusion These findings suggest synaptic pathophysiology is widespread in ALS-FTD and has an early and fundamental role in driving altered network function that is thought to contribute to neurodegenerative processes in these patients. The overall importance is the identification of previously unidentified defects in pre and postsynaptic compartments affecting synaptic plasticity, synaptic vesicle stores, and network propagation, which directly impact upon cortical function.

AMPA receptor-mediated regulation of a Gi-protein in cortical neurons

Nature ◽  
10.1038/39062 ◽  
1997 ◽  
Vol 389 (6650) ◽  
pp. 502-504 ◽  
Author(s):  
Yizheng Wang ◽  
Daniel L. Small ◽  
Danica B. Stanimirovic ◽  
Paul Morley ◽  
Jon P. Durkin
Keyword(s):  
Ampa Receptor ◽  
Cortical Neurons ◽  
Gi Protein

LY392098, a novel AMPA receptor potentiator: electrophysiological studies in prefrontal cortical neurons

2001 ◽  
Vol 40 (8) ◽  
pp. 992-1002 ◽  
Author(s):  
Polly Baumbarger ◽  
Mark Muhlhauser ◽  
Charles R Yang ◽  
Eric S Nisenbaum
Keyword(s):  
Ampa Receptor ◽  
Cortical Neurons ◽  
Prefrontal Cortical ◽  
Electrophysiological Studies

Stress hormones and AMPA receptor trafficking in synaptic plasticity and memory

2010 ◽  
Vol 11 (10) ◽  
pp. 675-681 ◽  
Author(s):  
Harmen J. Krugers ◽  
Casper C. Hoogenraad ◽  
Laurent Groc
Keyword(s):  
Synaptic Plasticity ◽  
Ampa Receptor ◽  
Stress Hormones ◽  
Receptor Trafficking ◽  
Ampa Receptor Trafficking

scholarly journals All-Trans Retinoic Acid induces synaptic plasticity in human cortical neurons

2020 ◽  
Author(s):  
Maximilian Lenz ◽  
Pia Kruse ◽  
Amelie Eichler ◽  
Julia Muellerleile ◽  
Jakob Straehle ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Synaptic Plasticity ◽  
Cortical Neurons ◽  
Mrna Translation ◽  
Dependent Manner ◽  
Human Cortex ◽  
Functional Changes ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Structural And Functional Properties

ABSTRACTA defining feature of the brain is its ability to adapt structural and functional properties of synaptic contacts in an experience-dependent manner. In the human cortex direct experimental evidence for synaptic plasticity is currently missing. Here, we probed plasticity in human cortical slices using the vitamin A derivative all-trans retinoic acid, which has been suggested as medication for the treatment of neuropsychiatric disorders, e.g., Alzheimer’s disease. Our experiments demonstrate coordinated structural and functional changes of excitatory synapses of superficial (layer 2/3) pyramidal neurons in the presence of all-trans retinoic acid. This synaptic adaptation is accompanied by ultrastructural remodeling of the calcium-storing spine apparatus organelle and requires mRNA-translation. We conclude that all-trans retinoic acid is a potent mediator of synaptic plasticity in the adult human cortex.

scholarly journals A role for cGMP-dependent protein kinase II in AMPA receptor trafficking and synaptic plasticity

2009 ◽  
Vol 9 (Suppl 1) ◽  
pp. S44 ◽  
Author(s):  
Yafelle Serulle ◽  
Ipe Ninan ◽  
Daniela Puzzo ◽  
Maria McCarthy ◽  
Latika Khatri ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Protein Kinase ◽  
Ampa Receptor ◽  
Receptor Trafficking ◽  
Dependent Protein Kinase ◽  
Cgmp Dependent Protein Kinase ◽  
Protein Kinase Ii ◽  
Dependent Protein ◽  
Ampa Receptor Trafficking

scholarly journals Phosphorylation of the AMPAR-TARP Complex in Synaptic Plasticity

Proteomes ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 40 ◽  
Author(s):  
Joongkyu Park
Keyword(s):  
Synaptic Plasticity ◽  
Drug Addiction ◽  
Ampa Receptor ◽  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Regulatory Proteins ◽  
Cellular Models ◽  
Brain Functions ◽  
Term Potentiation

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.

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