Dataset Information

NMDA-receptor antibodies alter cortical microcircuit dynamics.

ABSTRACT: NMDA-receptor antibodies (NMDAR-Abs) cause an autoimmune encephalitis with a diverse range of EEG abnormalities. NMDAR-Abs are believed to disrupt receptor function, but how blocking this excitatory synaptic receptor can lead to paroxysmal EEG abnormalities-or even seizures-is poorly understood. Here we show that NMDAR-Abs change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity and predispose brain dynamics to paroxysmal abnormalities. Based on local field potential recordings in a mouse model, we first validate a dynamic causal model of NMDAR-Ab effects on cortical microcircuitry. Using this model, we then identify the key synaptic parameters that best explain EEG paroxysms in pediatric patients with NMDAR-Ab encephalitis. Finally, we use the mouse model to show that NMDAR-Ab-related changes render microcircuitry critically susceptible to overt EEG paroxysms when these key parameters are changed, even though the same parameter fluctuations are tolerated in the in silico model of the control condition. These findings offer mechanistic insights into circuit-level dysfunction induced by NMDAR-Ab.

SUBMITTER: Rosch RE

PROVIDER: S-EPMC6196513 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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NMDA-receptor antibodies alter cortical microcircuit dynamics.

Rosch Richard E RE Wright Sukhvir S Cooray Gerald G Papadopoulou Margarita M Goyal Sushma S Lim Ming M Vincent Angela A Upton A Louise AL Baldeweg Torsten T Friston Karl J KJ

Proceedings of the National Academy of Sciences of the United States of America 20180927 42

NMDA-receptor antibodies (NMDAR-Abs) cause an autoimmune encephalitis with a diverse range of EEG abnormalities. NMDAR-Abs are believed to disrupt receptor function, but how blocking this excitatory synaptic receptor can lead to paroxysmal EEG abnormalities-or even seizures-is poorly understood. Here we show that NMDAR-Abs change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity and predispose brain dynamics to paroxysma ...[more]

PMID: 30262654

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NMDA-receptor antibodies alter cortical microcircuit dynamics.

Publications

NMDA-receptor antibodies alter cortical microcircuit dynamics.

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