scholarly journals Interleukin 10 Restores Lipopolysaccharide-Induced Alterations in Synaptic Plasticity Probed by Repetitive Magnetic Stimulation

2020 ◽  
Vol 11 ◽  
Author(s):  
Maximilian Lenz ◽  
Amelie Eichler ◽  
Pia Kruse ◽  
Andreas Strehl ◽  
Silvia Rodriguez-Rozada ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Systemic Inflammation ◽  
Magnetic Stimulation ◽  
Long Term Potentiation ◽  
Interleukin 10 ◽  
Brain Inflammation ◽  
Tissue Cultures ◽  
Brain Functions ◽  
Repetitive Magnetic Stimulation ◽  
Excitatory Neurotransmission

Systemic inflammation is associated with alterations in complex brain functions such as learning and memory. However, diagnostic approaches to functionally assess and quantify inflammation-associated alterations in synaptic plasticity are not well-established. In previous work, we demonstrated that bacterial lipopolysaccharide (LPS)-induced systemic inflammation alters the ability of hippocampal neurons to express synaptic plasticity, i.e., the long-term potentiation (LTP) of excitatory neurotransmission. Here, we tested whether synaptic plasticity induced by repetitive magnetic stimulation (rMS), a non-invasive brain stimulation technique used in clinical practice, is affected by LPS-induced inflammation. Specifically, we explored brain tissue cultures to learn more about the direct effects of LPS on neural tissue, and we tested for the plasticity-restoring effects of the anti-inflammatory cytokine interleukin 10 (IL10). As shown previously, 10 Hz repetitive magnetic stimulation (rMS) of organotypic entorhino-hippocampal tissue cultures induced a robust increase in excitatory neurotransmission onto CA1 pyramidal neurons. Furthermore, LPS-treated tissue cultures did not express rMS-induced synaptic plasticity. Live-cell microscopy in tissue cultures prepared from a novel transgenic reporter mouse line [C57BL/6-Tg(TNFa-eGFP)] confirms that ex vivo LPS administration triggers microglial tumor necrosis factor alpha (TNFα) expression, which is ameliorated in the presence of IL10. Consistent with this observation, IL10 hampers the LPS-induced increase in TNFα, IL6, IL1β, and IFNγ and restores the ability of neurons to express rMS-induced synaptic plasticity in the presence of LPS. These findings establish organotypic tissue cultures as a suitable model for studying inflammation-induced alterations in synaptic plasticity, thus providing a biological basis for the diagnostic use of transcranial magnetic stimulation in the context of brain inflammation.

scholarly journals Neural inflammation alters synaptic plasticity probed by 10 Hz repetitive magnetic stimulation

2020 ◽  
Author(s):  
Maximilian Lenz ◽  
Amelie Eichler ◽  
Pia Kruse ◽  
Andreas Strehl ◽  
Silvia Rodriguez-Rozada ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Systemic Inflammation ◽  
Magnetic Stimulation ◽  
Long Term Potentiation ◽  
Brain Inflammation ◽  
Suitable Model ◽  
Tissue Cultures ◽  
Brain Functions ◽  
Repetitive Magnetic Stimulation ◽  
Excitatory Neurotransmission

ABSTRACTSystemic inflammation is associated with alterations in complex brain functions such as learning and memory. However, diagnostic approaches to functionally assess and quantify inflammation-associated alterations in synaptic plasticity are not well-established. In previous work, we demonstrated that bacterial lipopolysaccharide (LPS)-induced systemic inflammation alters the ability of hippocampal neurons to express synaptic plasticity, i.e., the long-term potentiation (LTP) of excitatory neurotransmission. Here, we tested whether synaptic plasticity induced by repetitive magnetic stimulation (rMS), a non-invasive brain stimulation technique used in clinical practice, is affected by LPS-induced inflammation. Specifically, we explored brain tissue cultures to learn more about the direct effects of LPS on neural tissue, and we tested for the plasticity-restoring effects of the anti-inflammatory cytokine interleukin 10 (IL10). As shown previously, 10 Hz repetitive magnetic stimulation (rMS) of organotypic entorhino-hippocampal tissue cultures induced a robust increase in excitatory neurotransmission onto CA1 pyramidal neurons. Furthermore, LPS-treated tissue cultures did not express rMS-induced synaptic plasticity. Live-cell microscopy in tissue cultures prepared from a novel transgenic reporter mouse line [C57BL6-Tg(TNFa-eGFP)] confirms that ex vivo LPS administration triggers microglial tumor necrosis factor alpha (TNFα) expression, which is ameliorated in the presence of IL10. Consistent with this observation, IL10 hampers the LPS-induced increase in TNFα, IL6, IL1β, and IFNγ and restores the ability of neurons to express rMS-induced synaptic plasticity in the presence of LPS. These findings establish organotypic tissue cultures as a suitable model for studying inflammation-induced alterations in synaptic plasticity, thus providing a biological basis for the diagnostic use of transcranial magnetic stimulation in the context of brain inflammation.

scholarly journals Microglia mediate synaptic plasticity induced by 10 Hz repetitive magnetic stimulation

2021 ◽  
Author(s):  
Amelie Eichler ◽  
Dimitrios Kleidonas ◽  
Zsolt Turi ◽  
Matthias Kirsch ◽  
Dietmar Pfeifer ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Functional Properties ◽  
Magnetic Stimulation ◽  
Pyramidal Neurons ◽  
Therapeutic Effects ◽  
Tissue Cultures ◽  
Ca1 Pyramidal Neurons ◽  
Structural And Functional Properties ◽  
Repetitive Magnetic Stimulation

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that is widely used in clinical practice for therapeutic purposes. Nevertheless, the mechanisms that mediate its therapeutic effects remain poorly understood. Recent work implicates that microglia, the resident immune cells of the central nervous system, have a defined role in the regulation of physiological brain function, e.g. the expression of synaptic plasticity. Despite this observation, no evidence exists for a role of microglia in excitatory synaptic plasticity induced by rTMS. Here, we used repetitive magnetic stimulation of organotypic entorhino-hippocampal tissue cultures to test for the role of microglia in synaptic plasticity induced by 10 Hz repetitive magnetic stimulation (rMS). For this purpose, we performed PLX3397 (Pexidartinib) treatment to deplete microglia from tissue culture preparations. Using whole-cell patch-clamp recordings, live-cell microscopy, immunohistochemistry and transcriptome analysis, we assessed structural and functional properties of both CA1 pyramidal neurons and microglia to correlate the microglia phenotype to synaptic plasticity. PLX3397 treatment over 18 days reliably depletes microglia in tissue cultures, without affecting structural and functional properties of CA1 pyramidal neurons. Microglia-depleted cultures display defects in the ability of CA1 pyramidal neurons to express plasticity of excitatory synapses upon rMS. Notably, rMS induces a moderate release of proinflammatory and plasticity-promoting factors, while microglial morphology stays unaltered. We conclude that microglia play a crucial role in rMS-induced excitatory synaptic plasticity.

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.

scholarly journals Chemical LTD, but not LTP, induces transient accumulation of gelsolin in dendritic spines

2019 ◽  
Vol 400 (9) ◽  
pp. 1129-1139 ◽  
Author(s):  
Iryna Hlushchenko ◽  
Pirta Hotulainen
Keyword(s):  
Synaptic Plasticity ◽  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Excitatory Synapses ◽  
Signal Molecule ◽  
Brain Functions ◽  
Dendritic Shaft ◽  
Term Potentiation

Abstract Synaptic plasticity underlies central brain functions, such as learning. Ca2+ signaling is involved in both strengthening and weakening of synapses, but it is still unclear how one signal molecule can induce two opposite outcomes. By identifying molecules, which can distinguish between signaling leading to weakening or strengthening, we can improve our understanding of how synaptic plasticity is regulated. Here, we tested gelsolin’s response to the induction of chemical long-term potentiation (cLTP) or long-term depression (cLTD) in cultured rat hippocampal neurons. We show that gelsolin relocates from the dendritic shaft to dendritic spines upon cLTD induction while it did not show any relocalization upon cLTP induction. Dendritic spines are small actin-rich protrusions on dendrites, where LTD/LTP-responsive excitatory synapses are located. We propose that the LTD-induced modest – but relatively long-lasting – elevation of Ca2+ concentration increases the affinity of gelsolin to F-actin. As F-actin is enriched in dendritic spines, it is probable that increased affinity to F-actin induces the relocalization of gelsolin.

scholarly journals Cannabinoid receptors contribute to astroglial Ca 2+ -signalling and control of synaptic plasticity in the neocortex

2014 ◽  
Vol 369 (1654) ◽  
pp. 20140077 ◽  
Author(s):  
Seyed Rasooli-Nejad ◽  
Oleg Palygin ◽  
Ulyana Lalo ◽  
Yuriy Pankratov
Keyword(s):  
Synaptic Plasticity ◽  
Gaba Receptors ◽  
Cannabinoid Receptors ◽  
Pyramidal Neurons ◽  
Atp Release ◽  
Long Term Potentiation ◽  
Dominant Negative ◽  
Snare Complex ◽  
Brain Functions ◽  
Cortical Pyramidal Neurons

Communication between neuronal and glial cells is thought to be very important for many brain functions. Acting via release of gliotransmitters, astrocytes can modulate synaptic strength. The mechanisms underlying ATP release from astrocytes remain uncertain with exocytosis being the most intriguing and debated pathway. We have demonstrated that ATP and d -serine can be released from cortical astrocytes in situ by a SNARE-complex-dependent mechanism. Exocytosis of ATP from astrocytes can activate post-synaptic P2X receptors in the adjacent neurons, causing a downregulation of synaptic and extrasynaptic GABA receptors in cortical pyramidal neurons. We showed that release of gliotransmitters is important for the NMDA receptor-dependent synaptic plasticity in the neocortex. Firstly, induction of long-term potentiation (LTP) by five episodes of theta-burst stimulation (TBS) was impaired in the neocortex of dominant-negative (dn)-SNARE mice. The LTP was rescued in the dn-SNARE mice by application of exogenous non-hydrolysable ATP analogues. Secondly, we observed that weak sub-threshold stimulation (two TBS episodes) became able to induce LTP when astrocytes were additionally activated via CB-1 receptors. This facilitation was dependent on activity of ATP receptors and was abolished in the dn-SNARE mice. Our results strongly support the physiological relevance of glial exocytosis for glia–neuron communications and brain function.

scholarly journals GRIP1 regulates synaptic plasticity and learning and memory

2020 ◽  
Vol 117 (40) ◽  
pp. 25085-25091
Author(s):  
Han L. Tan ◽  
Shu-Ling Chiu ◽  
Qianwen Zhu ◽  
Richard L. Huganir
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Postsynaptic Membrane ◽  
Interacting Protein ◽  
Synaptic Targeting ◽  
Brain Functions ◽  
Ampar Trafficking

Hebbian plasticity is a key mechanism for higher brain functions, such as learning and memory. This form of synaptic plasticity primarily involves the regulation of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) abundance and properties, whereby AMPARs are inserted into synapses during long-term potentiation (LTP) or removed during long-term depression (LTD). The molecular mechanisms underlying AMPAR trafficking remain elusive, however. Here we show that glutamate receptor interacting protein 1 (GRIP1), an AMPAR-binding protein shown to regulate the trafficking and synaptic targeting of AMPARs, is required for LTP and learning and memory. GRIP1 is recruited into synapses during LTP, and deletion of Grip1 in neurons blocks synaptic AMPAR accumulation induced by glycine-mediated depolarization. In addition, Grip1 knockout mice exhibit impaired hippocampal LTP, as well as deficits in learning and memory. Mechanistically, we find that phosphorylation of serine-880 of the GluA2 AMPAR subunit (GluA2-S880) is decreased while phosphorylation of tyrosine-876 on GluA2 (GluA2-Y876) is elevated during chemically induced LTP. This enhances the strength of the GRIP1–AMPAR association and, subsequently, the insertion of AMPARs into the postsynaptic membrane. Together, these results demonstrate an essential role of GRIP1 in regulating AMPAR trafficking during synaptic plasticity and learning and memory.

scholarly journals Lipopolysaccharide-Induced Spatial Memory and Synaptic Plasticity Impairment Is Preventable by Captopril

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Azam Abareshi ◽  
Akbar Anaeigoudari ◽  
Fatemeh Norouzi ◽  
Mohammad Naser Shafei ◽  
Mohammad Hossein Boskabady ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Spatial Memory ◽  
Renin Angiotensin System ◽  
Long Term Potentiation ◽  
Control Group ◽  
Excitatory Postsynaptic Potential ◽  
Memory Impairments ◽  
Brain Functions ◽  
Responsible Mechanism ◽  
Ca1 Area

Introduction.Renin-angiotensin system has a role in inflammation and also is involved in many brain functions such as learning, memory, and emotion. Neuroimmune factors have been proposed as the contributors to the pathogenesis of memory impairments. In the present study, the effect of captopril on spatial memory and synaptic plasticity impairments induced by lipopolysaccharide (LPS) was investigated.Methods.The rats were divided and treated into control (saline), LPS (1 mg/kg), LPS-captopril (LPS-Capto; 50 mg/kg captopril before LPS), and captopril groups (50 mg/kg) before saline. Morris water maze was done. Long-term potentiation (LTP) from CA1 area of hippocampus was assessed by 100 Hz stimulation in the ipsilateral Schaffer collateral pathway.Results.In the LPS group, the spent time and traveled path to reach the platform were longer than those in the control, while, in the LPS-Capto group, they were shorter than those in the LPS group. Moreover, the slope and amplitude of field excitatory postsynaptic potential (fEPSP) decreased in the LPS group, as compared to the control group, whereas, in the LPS-Capto group, they increased compared to the LPS group.Conclusion.The results of the present study showed that captopril improved the LPS-induced memory and LTP impairments induced by LPS in rats. Further investigations are required in order to better understand the exact responsible mechanism(s).

scholarly journals The interplay between Hebbian and homeostatic synaptic plasticity

2013 ◽  
Vol 203 (2) ◽  
pp. 175-186 ◽  
Author(s):  
Nathalia Vitureira ◽  
Yukiko Goda
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Network Activity ◽  
Cellular Mechanisms ◽  
Brain Functions ◽  
Strength Change ◽  
Neuronal Network Activity ◽  
Homeostatic Synaptic Plasticity ◽  
New Findings

Synaptic plasticity, a change in the efficacy of synaptic signaling, is a key property of synaptic communication that is vital to many brain functions. Hebbian forms of long-lasting synaptic plasticity—long-term potentiation (LTP) and long-term depression (LTD)—have been well studied and are considered to be the cellular basis for particular types of memory. Recently, homeostatic synaptic plasticity, a compensatory form of synaptic strength change, has attracted attention as a cellular mechanism that counteracts changes brought about by LTP and LTD to help stabilize neuronal network activity. New findings on the cellular mechanisms and molecular players of the two forms of plasticity are uncovering the interplay between them in individual neurons.

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