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 ◽  
...  

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.

2020 ◽  
Author(s):  
Maximilian Lenz ◽  
Amelie Eichler ◽  
Pia Kruse ◽  
Andreas Strehl ◽  
Silvia Rodriguez-Rozada ◽  
...  

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.


2020 ◽  
Vol 11 ◽  
Author(s):  
Maximilian Lenz ◽  
Amelie Eichler ◽  
Pia Kruse ◽  
Andreas Strehl ◽  
Silvia Rodriguez-Rozada ◽  
...  

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.


eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Il Hwan Kim ◽  
Hong Wang ◽  
Scott H Soderling ◽  
Ryohei Yasuda

Cdc42 is a signaling protein important for reorganization of actin cytoskeleton and morphogenesis of cells. However, the functional role of Cdc42 in synaptic plasticity and in behaviors such as learning and memory are not well understood. Here we report that postnatal forebrain deletion of Cdc42 leads to deficits in synaptic plasticity and in remote memory recall using conditional knockout of Cdc42. We found that deletion of Cdc42 impaired LTP in the Schaffer collateral synapses and postsynaptic structural plasticity of dendritic spines in CA1 pyramidal neurons in the hippocampus. Additionally, loss of Cdc42 did not affect memory acquisition, but instead significantly impaired remote memory recall. Together these results indicate that the postnatal functions of Cdc42 may be crucial for the synaptic plasticity in hippocampal neurons, which contribute to the capacity for remote memory recall.


2014 ◽  
Vol 220 (6) ◽  
pp. 3323-3337 ◽  
Author(s):  
Maximilian Lenz ◽  
Steffen Platschek ◽  
Viola Priesemann ◽  
Denise Becker ◽  
Laurent M. Willems ◽  
...  

Nutrients ◽  
2018 ◽  
Vol 10 (6) ◽  
pp. 749 ◽  
Author(s):  
Stine Hansen ◽  
Jane Jørgensen ◽  
Jens Nyengaard ◽  
Jens Lykkesfeldt ◽  
Pernille Tveden-Nyborg

2016 ◽  
Vol 28 (6) ◽  
pp. 4914-4924 ◽  
Author(s):  
Tapati Sarkar ◽  
Sergey A. Ivanov ◽  
Elena A. Fortalnova ◽  
Ekaterina D. Politova ◽  
Marina G. Safronenko ◽  
...  

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