scholarly journals Critical Role of CDK5 and Polo-like Kinase 2 in Homeostatic Synaptic Plasticity during Elevated Activity

Neuron ◽  
2008 ◽  
Vol 58 (4) ◽  
pp. 571-583 ◽  
Author(s):  
Daniel P. Seeburg ◽  
Monica Feliu-Mojer ◽  
Johanna Gaiottino ◽  
Daniel T.S. Pak ◽  
Morgan Sheng
Keyword(s):  
Synaptic Plasticity ◽  
Critical Role ◽  
Homeostatic Synaptic Plasticity ◽  
Elevated Activity

scholarly journals Calcineurin mediates homeostatic synaptic plasticity by regulating retinoic acid synthesis

2015 ◽  
Vol 112 (42) ◽  
pp. E5744-E5752 ◽  
Author(s):  
Kristin L. Arendt ◽  
Zhenjie Zhang ◽  
Subhashree Ganesan ◽  
Maik Hintze ◽  
Maggie M. Shin ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Critical Role ◽  
Signal Transduction Pathway ◽  
Acid Synthesis ◽  
Synaptic Activity ◽  
Homeostatic Synaptic Plasticity ◽  
Dependent Protein

Homeostatic synaptic plasticity is a form of non-Hebbian plasticity that maintains stability of the network and fidelity for information processing in response to prolonged perturbation of network and synaptic activity. Prolonged blockade of synaptic activity decreases resting Ca2+ levels in neurons, thereby inducing retinoic acid (RA) synthesis and RA-dependent homeostatic synaptic plasticity; however, the signal transduction pathway that links reduced Ca2+-levels to RA synthesis remains unknown. Here we identify the Ca2+-dependent protein phosphatase calcineurin (CaN) as a key regulator for RA synthesis and homeostatic synaptic plasticity. Prolonged inhibition of CaN activity promotes RA synthesis in neurons, and leads to increased excitatory and decreased inhibitory synaptic transmission. These effects of CaN inhibitors on synaptic transmission are blocked by pharmacological inhibitors of RA synthesis or acute genetic deletion of the RA receptor RARα. Thus, CaN, acting upstream of RA, plays a critical role in gating RA signaling pathway in response to synaptic activity. Moreover, activity blockade-induced homeostatic synaptic plasticity is absent in CaN knockout neurons, demonstrating the essential role of CaN in RA-dependent homeostatic synaptic plasticity. Interestingly, in GluA1 S831A and S845A knockin mice, CaN inhibitor- and RA-induced regulation of synaptic transmission is intact, suggesting that phosphorylation of GluA1 C-terminal serine residues S831 and S845 is not required for CaN inhibitor- or RA-induced homeostatic synaptic plasticity. Thus, our study uncovers an unforeseen role of CaN in postsynaptic signaling, and defines CaN as the Ca2+-sensing signaling molecule that mediates RA-dependent homeostatic synaptic plasticity.

scholarly journals Role of neuronal activity and metaplastic state in homeostatic synaptic plasticity

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S402-S403
Author(s):  
Bryce Grier ◽  
Varun Chokshi ◽  
Andrew Dykman ◽  
Crystal Lantz ◽  
Ernst Niebur ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Activity ◽  
Homeostatic Synaptic Plasticity

scholarly journals Inhibition of Endoplasmic Reticulum Stress Reverses Synaptic Plasticity Deficits in Striatum of DYT1 Dystonia Mice

2021 ◽  
Author(s):  
Huaying Cai ◽  
Linhui Ni ◽  
Xingyue Hu ◽  
Xianjun Ding
Keyword(s):  
Endoplasmic Reticulum ◽  
Synaptic Plasticity ◽  
Er Stress ◽  
Critical Role ◽  
Stress Protein ◽  
Long Term Potentiation ◽  
Research Field ◽  
Protein Levels ◽  
Dyt1 Dystonia

Abstract Background & objectiveStriatal plasticity alterations caused by endoplasmic reticulum (ER) stress is supposed to be critically involved in the mechanism of DYT1 dystonia. In the current study, we expanded this research field by investigating the critical role of ER stress underlying synaptic plasticity impairment imposed by mutant heterozygous Tor1a+/- in a DYT1 dystonia mouse model.Methods & resultsLong-term depression (LTD) was failed to be induced, while long-term potentiation (LTP) was further strengthened in striatal spiny neurons (SPNs) from the Tor1a+/- DYT1 dystonia mice. Spine morphology analyses revealed a significant increase of both number of mushroom type spines and spine width in Tor1a+/- SPNs. In addition, increased AMPA receptor function and the reduction of NMDA/AMPA ratio in the postsynaptic of Tor1a+/- SPNs was observed, along with increased ER stress protein levels in Tor1a+/- striatum. Notably, ER stress inhibitors, tauroursodeoxycholic acid (TUDCA), could rescue LTD as well as AMPA currents.ConclusionThe current study illustrated the role of ER stress in mediating structural and functional plasticity alterations in Tor1a+/- SPNs. Inhibition of the ER stress by TUDCA is beneficial in reversing the deficits at the cellular and molecular levels. Remedy of dystonia associated neurological and motor functional impairment by ER stress inhibitors could be a recommendable therapeutic agent in clinical practice.

scholarly journals Amyloid-beta mediates homeostatic synaptic plasticity

2020 ◽  
Author(s):  
Christos Galanis ◽  
Meike Fellenz ◽  
Denise Becker ◽  
Charlotte Bold ◽  
Stefan F. Lichtenthaler ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Granule Cells ◽  
Amyloid Β ◽  
Physiological Role ◽  
Homeostatic Plasticity ◽  
App Processing ◽  
Brain Physiology ◽  
Homeostatic Synaptic Plasticity ◽  
Organotypic Tissue

ABSTRACTThe physiological role of the amyloid-precursor protein (APP) is insufficiently understood. Recent work has implicated APP in the regulation of synaptic plasticity. Substantial evidence exists for a role of APP and its secreted ectodomain APPsα in Hebbian plasticity. Here, we addressed the relevance of APP in homeostatic synaptic plasticity using organotypic tissue cultures of APP−/− mice. In the absence of APP, dentate granule cells failed to strengthen their excitatory synapses homeostatically. Homeostatic plasticity is rescued by amyloid-β (Aβ) and not by APPsα, and it is neither observed in APP+/+ tissue treated with β- or γ-secretase inhibitors nor in synaptopodin-deficient cultures lacking the Ca2+-dependent molecular machinery of the spine apparatus. Together, these results suggest a role of APP processing via the amyloidogenic pathway in homeostatic synaptic plasticity, representing a function of relevance for brain physiology as well as for brain states associated with increased Aβ levels.

scholarly journals Critical role of promoter IV-driven BDNF transcription in GABAergic transmission and synaptic plasticity in the prefrontal cortex

2009 ◽  
Vol 106 (14) ◽  
pp. 5942-5947 ◽  
Author(s):  
K. Sakata ◽  
N. H. Woo ◽  
K. Martinowich ◽  
J. S. Greene ◽  
R. J. Schloesser ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Plasticity ◽  
Critical Role ◽  
Gabaergic Transmission ◽  
Bdnf Transcription

Regulation of Synaptic Homeostasis by Translational Mechanisms

2019 ◽  
Author(s):  
Megumi Mori ◽  
Jay Penney ◽  
Pejmun Haghighi
Keyword(s):  
Synaptic Plasticity ◽  
Neurotransmitter Release ◽  
Critical Role ◽  
Synaptic Homeostasis ◽  
Brain Functions ◽  
Homeostatic Synaptic Plasticity ◽  
Cellular Context ◽  
Translational Mechanisms ◽  
Higher Brain Functions ◽  
Synaptic Mechanisms

The ability of synapses to modify their functional properties and adjust the amount of neurotransmitter release at their terminals is essential for formation of appropriate neural circuits during development and crucial for higher brain functions throughout life. Many forms of synaptic plasticity can adjust synaptic strength down (depression) or up (potentiation); however, depending on the cellular context as the forces of change act upon the synapse, other synaptic mechanisms are activated to resist change. This form of synaptic plasticity is generally referred to as homeostatic synaptic plasticity. Accumulating experimental evidence indicates that translational mechanisms play a critical role in the regulation of homeostatic synaptic plasticity. This chapter will review studies that contribute to this body of evidence, including a role for the target of rapamycin in the retrograde regulation of synaptic homeostasis.

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