scholarly journals Homeostatic Synaptic Plasticity: Balanced by COX2-PGE2 System to a New Setpoint

2013 ◽  
Vol 1 (2) ◽  
pp. 20-23
Author(s):  
Fuzhou Wang
Keyword(s):  
Nervous System ◽  
Synaptic Plasticity ◽  
Prostaglandin E2 ◽  
Neural Activity ◽  
Neural Circuits ◽  
Critical Role ◽  
Homeostatic Plasticity ◽  
Homeostatic Synaptic Plasticity ◽  
Cox 2

The setpoint of neural activity plays a critical role in maintaining the complex neural circuits into stable activities. Homeostatic synaptic plasticity is a major component of the setpoint theory that dynamically adjusts synaptic strengths. Cyclooxy-genase 2 (COX 2) is rapidly upregulated in inflammatory episodes after nervous injury and its product prostaglandin E2 (PGE2) exerts contrast functions in the nervous system by working on the homeostatic plasticity. New data revealed that COX2-PGE2 system takes an essential part in balancing excitation and inhibition of the synaptic activities at a new setpoint that finally is maintained by the homeostatic synaptic plasticity.

scholarly journals Synapse-Specific Homeostatic Mechanisms in the Hippocampus

2009 ◽  
Vol 101 (2) ◽  
pp. 503-506 ◽  
Author(s):  
Katherine E. Deeg
Keyword(s):  
Neural Circuits ◽  
Epileptic Seizures ◽  
Homeostatic Plasticity ◽  
Excitatory Synapses ◽  
Network Stability ◽  
Homeostatic Synaptic Plasticity ◽  
New Type ◽  
Hippocampal Network ◽  
Synaptic Gain ◽  
Different Populations

Homeostatic synaptic plasticity allows neural circuits to function stably despite fluctuations to their inputs. Previous work has shown that excitatory synaptic strength increases globally when neuronal inputs are chronically silenced. A recent paper by Kim and Tsien describes a new type of synapse-specific homeostatic plasticity in which input silencing causes simultaneous strengthening and weakening of different populations of excitatory synapses within a hippocampal network. These seemingly antagonistic homeostatic adaptations maintain synaptic gain and preserve overall network stability by limiting harmful reverberatory bursting, which may underlie epileptic seizures.

scholarly journals Homeostatic Plasticity Hypothesis and Mechanisms of Neocortical Epilepsies

2005 ◽  
Vol 5 (4) ◽  
pp. 133-135 ◽  
Author(s):  
Jaideep Kapur ◽  
Stacey Trotter
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Activity ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Homeostatic Plasticity ◽  
Excitatory Synapses ◽  
Excitatory Postsynaptic Currents ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Homeostatic Synaptic Plasticity

Homeostatic Synaptic Plasticity Can Explain Posttraumatic Epileptogenesis in Chronically Isolated Neocortex Houweling AR, Bazhenov M, Timofeev I, Steriade M, Sejnowski TJ Cereb Cortex 2004 [Epub ahead of print] Permanently isolated neocortex develops chronic hyperexcitability and focal epileptogenesis in a period of days to weeks. The mechanisms operating in this model of posttraumatic epileptogenesis are not well understood. We hypothesized that the spontaneous burst discharges recorded in permanently isolated neocortex result from homeostatic plasticity (a mechanism generally assumed to stabilize neuronal activity) induced by low neuronal activity after deafferentation. To test this hypothesis, we constructed computer models of neocortex incorporating a biologically based homeostatic plasticity rule that operates to maintain firing rates. After deafferentation, homeostatic upregulation of excitatory synapses on pyramidal cells, either with or without concurrent downregulation of inhibitory synapses or upregulation of intrinsic excitability, initiated slowly repeating burst discharges that closely resembled the epileptiform burst discharges recorded in permanently isolated neocortex. These burst discharges lasted a few hundred milliseconds, propagated at 1 to 3 cm/s and consisted of large (10–15 mV) intracellular depolarizations topped by a small number of action potentials. Our results support a role for homeostatic synaptic plasticity as a novel mechanism of posttraumatic epileptogenesis. Excitatory and Inhibitory Postsynaptic Currents in a Rat Model of Epileptogenic Microgyria Jacobs KM, Prince DA J Neurophysiol 2005;93:687–696 Developmental cortical malformations are common in patients with intractable epilepsy; however, mechanisms contributing to this epileptogenesis are currently poorly understood. We previously characterized hyperexcitability in a rat model that mimics the histopathology of human four-layered microgyria. Here we examined inhibitory and excitatory postsynaptic currents in this model to identify functional alterations that might contribute to epileptogenesis associated with microgyria. We recorded isolated whole-cell excitatory postsynaptic currents and GABAA receptor–mediated inhibitory currents from layer V pyramidal neurons in the region previously shown to be epileptogenic (paramicrogyral area) and in homotopic control cortex. Epileptiform-like activity could be evoked in 60% of paramicrogyral (PMG) cells by local stimulation. The peak conductance of both spontaneous and evoked inhibitory postsynaptic currents was significantly larger in all PMG cells compared with controls. This difference in amplitude was not present after blockade of ionotropic glutamatergic currents or for miniature (m) inhibitory postsynaptic currents, suggesting that it was due to the excitatory afferent activity driving inhibitory neurons. This conclusion was supported by the finding that glutamatereceptor antagonist application resulted in a significantly greater reduction in spontaneous inhibitory postsynaptic current frequency in one PMG cell group (PMGE) compared with control cells. The frequency of both spontaneous and miniature excitatory postsynaptic currents was significantly greater in all PMG cells, suggesting that pyramidal neurons adjacent to a microgyrus receive more excitatory input than do those in control cortex. These findings suggest that there is an increase in numbers of functional excitatory synapses on both interneurons and pyramidal cells in the PMG cortex, perhaps due to hyperinnervation by cortical afferents originally destined for the microgyrus proper.

scholarly journals KIF2C regulates synaptic plasticity and cognition by mediating dynamic microtubule invasion of dendritic spines

2021 ◽  
Author(s):  
Rui Zheng ◽  
Yonglan Du ◽  
Xintai Wang ◽  
Tailin Liao ◽  
Zhe Zhang ◽  
...  
Keyword(s):  
Nervous System ◽  
Synaptic Plasticity ◽  
Cell Structure ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Conditional Knockout ◽  
Synaptic Membrane ◽  
Dependent Manner ◽  
Microtubule Depolymerization ◽  
Dynamic Microtubule

Dynamic microtubules play a critical role in cell structure and function. In nervous system, microtubules specially extend into and out of synapses to regulate synaptic development and plasticity. However, the detailed polymerization especially the depolymerization mechanism that regulates dynamic microtubules in synapses is still unclear. In this study, we find that KIF2C, a dynamic microtubule depolymerization protein without known function in the nervous system, plays a vital role in the structural and functional plasticity of synapses and regulates cognitive function. Using RNAi knockdown and conditional knockout approaches, we showed that KIF2C regulates spine morphology and synaptic membrane expression of AMPA (α- amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) receptors. Moreover, KIF2C deficiency leads to impaired excitatory transmission, long-term potentiation, and altered cognitive behaviors in mice. Mechanistically, KIF2C regulates microtubule dynamics and microtubule invasion of spines in neurons by its microtubule depolymerization capability in a neuronal activity-dependent manner. This study explores a novel function of KIF2C in the nervous system and provides an important regulatory mechanism on how microtubule invasion of spines regulates synaptic plasticity and cognition behaviors.

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 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 AMPA Receptor Trafficking in Homeostatic Synaptic Plasticity: Functional Molecules and Signaling Cascades

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Guan Wang ◽  
James Gilbert ◽  
Heng-Ye Man
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Firing ◽  
Synaptic Activity ◽  
Homeostatic Plasticity ◽  
Signaling Cascades ◽  
Excitatory Synapses ◽  
Homeostatic Synaptic Plasticity ◽  
Ampar Trafficking ◽  
Entire Network ◽  
Homeostatic Response

Homeostatic synaptic plasticity is a negative-feedback response employed to compensate for functional disturbances in the nervous system. Typically, synaptic activity is strengthened when neuronal firing is chronically suppressed or weakened when neuronal activity is chronically elevated. At both the whole cell and entire network levels, activity manipulation leads to a global up- or downscaling of the transmission efficacy of all synapses. However, the homeostatic response can also be induced locally at subcellular regions or individual synapses. Homeostatic synaptic scaling is expressed mainly via the regulation ofα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking and synaptic expression. Here we review the recently identified functional molecules and signaling pathways that are involved in homeostatic plasticity, especially the homeostatic regulation of AMPAR localization at excitatory synapses.

scholarly journals Wherefore Art Thou, Homeo(stasis)? Functional Diversity in Homeostatic Synaptic Plasticity

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Bridget N. Queenan ◽  
Kea Joo Lee ◽  
Daniel T. S. Pak
Keyword(s):  
Synaptic Plasticity ◽  
Homeostatic Plasticity ◽  
Network Activity ◽  
Control Mechanisms ◽  
Adaptive Responses ◽  
Neuronal Function ◽  
Homeostatic Synaptic Plasticity ◽  
Regulatory Principle ◽  
Functional Classes ◽  
Homeostatic Mechanisms

Homeostatic plasticity has emerged as a fundamental regulatory principle that strives to maintain neuronal activity within optimal ranges by altering diverse aspects of neuronal function. Adaptation to network activity is often viewed as an essential negative feedback restraint that prevents runaway excitation or inhibition. However, the precise importance of these homeostatic functions is often theoretical rather than empirically derived. Moreover, a remarkable multiplicity of homeostatic adaptations has been observed. To clarify these issues, it may prove useful to ask: why do homeostatic mechanisms exist, what advantages do these adaptive responses confer on a given cell population, and why are there so many seemingly divergent effects? Here, we approach these questions by applying the principles of control theory to homeostatic synaptic plasticity of mammalian neurons and suggest that the varied responses observed may represent distinct functional classes of control mechanisms directed toward disparate physiological goals.

scholarly journals Upregulation of Cytokines and Differentiation of Th17 and Treg by Dendritic Cells: Central Role of Prostaglandin E2 Induced by Mycobacterium bovis

2020 ◽  
Vol 8 (2) ◽  
pp. 195 ◽  
Author(s):  
Han Liu ◽  
Xuekai Xiong ◽  
Wenjun Zhai ◽  
Tingting Zhu ◽  
Xiaojie Zhu ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Prostaglandin E2 ◽  
Mycobacterium Bovis ◽  
Cd4 T Cells ◽  
Th17 Cell ◽  
Critical Role ◽  
Protein Detection ◽  
Cox Inhibitor ◽  
Cox 2

Mycobacterium bovis (M. bovis) is a zoonotic pathogen that causes bovine and human tuberculosis. Dendritic cells play a critical role in initiating and regulating immune responses by promoting antigen-specific T-cell activation. Prostaglandin E2 (PGE2)-COX signaling is an important mediator of inflammation and immunity and might be involved in the pathogenesis of M. bovis infection. Therefore, this study aimed to reveal the character of PGE2 in the differentiation of naïve CD4+ T cells induced by infected dendritic cells (DCs). Murine bone marrow-derived DCs were pre-infected with M. bovis and its attenuated strain M. bovis bacillus Calmette-Guérin (BCG). Then, the infected DCs were co-cultured with naïve CD4+ T cells with or without the cyclooxygenase (COX) inhibitor indomethacin. Quantitative RT-PCR analysis and protein detection showed that PGE2/COX-2 signaling was activated, shown by the upregulation of PGE2 production as well as COX-2 and microsomal PGE2 synthase (mPGES1) transcription in DCs specifically induced by M. bovis and BCG infection. The further co-culture of infected DCs with naïve CD4+ T cells enhanced the generation of inflammatory cytokines IL-17 and IL-23, while indomethacin suppressed their production. Following this, the differentiation of regulatory T cells (Treg) and Th17 cell subsets was significantly induced by the infected DCs rather than uninfected DCs. Meanwhile, M. bovis infection stimulated significantly higher levels of IL-17 and IL-23 and the differentiation of Treg and Th17 cell subsets, while BCG infection led to higher levels of TNF-α and IL-12, but lower proportions of Treg and Th17 cells. In mice, M. bovis infection generated more bacterial load and severe abnormalities in spleens and lungs, as well as higher levels of COX-2, mPGE2 expression, Treg and Th17 cell subsets than BCG infection. In conclusion, PGE2/COX-2 signaling was activated in DCs by M. bovis infection and regulated differentiation of Treg and Th17 cell subsets through the crosstalk between DCs and naive T cells under the cytokine atmosphere of IL-17 and IL-23, which might contribute to M. bovis pathogenesis in mice.

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.

scholarly journals FMRP Interacts with RARα in Synaptic Retinoic Acid Signaling and Homeostatic Synaptic Plasticity

2021 ◽  
Vol 22 (12) ◽  
pp. 6579
Author(s):  
Esther Park ◽  
Anthony G. Lau ◽  
Kristin L. Arendt ◽  
Lu Chen
Keyword(s):  
Mental Retardation ◽  
Retinoic Acid ◽  
Synaptic Plasticity ◽  
Fragile X ◽  
Neurodevelopmental Disorder ◽  
Synaptic Function ◽  
Homeostatic Plasticity ◽  
Fragile X Mental Retardation ◽  
Severe Intellectual Disability ◽  
Homeostatic Synaptic Plasticity

The fragile X syndrome (FXS) is an X-chromosome-linked neurodevelopmental disorder with severe intellectual disability caused by inactivation of the fragile X mental retardation 1 (FMR1) gene and subsequent loss of the fragile X mental retardation protein (FMRP). Among the various types of abnormal synaptic function and synaptic plasticity phenotypes reported in FXS animal models, defective synaptic retinoic acid (RA) signaling and subsequent defective homeostatic plasticity have emerged as a major synaptic dysfunction. However, the mechanism underlying the defective synaptic RA signaling in the absence of FMRP is unknown. Here, we show that RARα, the RA receptor critically involved in synaptic RA signaling, directly interacts with FMRP. This interaction is enhanced in the presence of RA. Blocking the interaction between FMRP and RARα with a small peptide corresponding to the critical binding site in RARα abolishes RA-induced increases in excitatory synaptic transmission, recapitulating the phenotype seen in the Fmr1 knockout mouse. Taken together, these data suggest that not only are functional FMRP and RARα necessary for RA-dependent homeostatic synaptic plasticity, but that the interaction between these two proteins is essential for proper transcription-independent RA signaling. Our results may provide further mechanistic understanding into FXS synaptic pathophysiology.

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