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

Lenz, M.; Eichler, A.; Kruse, P.; Strehl, A.; Rodriguez-Rozada, S.; Goren, I.; Yogev, N.; Frank, S.; Waisman, A.; Deller, T.; Jung, S.; Maggio, N.; Vlachos, A.

doi:10.1101/2020.10.16.336065

bioRxiv · 10.1101/2020.10.16.336065

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

Lenz, M.·Eichler, A.·Kruse, P.·Strehl, A.·Rodriguez-Rozada, S.·Goren, I.·Yogev, N.·Frank, S.·Waisman, A.·Deller, T.·Jung, S.·Maggio, N.·Vlachos, A.

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Abstract

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 [C57BL6-Tg(TNFa-eGFP)] confirms that ex vivo LPS administration triggers microglial tumor necrosis factor alpha (TNF) expression, which is ameliorated in the presence of IL10. Consistent with this observation, IL10 hampers the LPS-induced increase in TNF, IL6, IL1{beta}, and IFN{gamma} 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.

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Lenz, M., Eichler, A., Kruse, P., Strehl, A., Rodriguez-Rozada, S., Goren, I., Yogev, N., Frank, S., Waisman, A., Deller, T., Jung, S., Maggio, N., Vlachos, A.. 2020-10-16. Neural inflammation alters synaptic plasticity probed by 10 Hz repetitive magnetic stimulation. https://doi.org/10.1101/2020.10.16.336065

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