Systemic administration of lipopolysaccharide induces hyperexcitability of prelimbic neurons via modulation of sodium and potassium currents
In C57BL/6 J mice, systemic inflammation was induced by administering bacterial LPS (1 mg/kg) intraperitoneally. In response, animals exhibited hypokinesia, piloerection, and a slight decrease in body temperature accompanied by increased serum levels of the proinflammatory cytokine TNF-α. 24 h after...
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Veröffentlicht in: | Neurotoxicology (Park Forest South) 2022-07, Vol.91, p.128-139 |
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Sprache: | eng |
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Zusammenfassung: | In C57BL/6 J mice, systemic inflammation was induced by administering bacterial LPS (1 mg/kg) intraperitoneally. In response, animals exhibited hypokinesia, piloerection, and a slight decrease in body temperature accompanied by increased serum levels of the proinflammatory cytokine TNF-α. 24 h after the immunogenic challenge, acute cortical slices were prepared, and whole-cell patch-clamp recordings were performed in morphologically identified prelimbic neurons of the mice’s prefrontal cortex. Electrophysiologic alterations included changes in the kinetics parameters of the fast-inactivating sodium and slow-inactivating potassium currents. In current-clamp mode, our recordings revealed alterations in several conductances that shape the intrinsic excitability of prelimbic neurons. The action potential exhibited changes in latency, amplitude, and the rheobase current to elicit firing discharge. Likewise, phase plots of the action potentials uncovered alterations in the repetitive firing of prelimbic neurons. Consistent with these changes, the afterhyperpolarization conductance and the slowly decaying, calcium‐dependent after-hyperpolarization current that follows an action potential were decreased in response to systemic LPS. Our data demonstrate that immune activation alters the ionic currents that shape the intrinsic excitability and predicts dysregulation of non-synaptic forms of neuronal plasticity modulated by the intrinsic excitability of prefrontal cortex neurons.
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•Immune activation by LPS alters biophysical properties of the Na+ currents.•Systemic LPS modifies biophysical properties of several K+ currents.•Systemic LPS increases the intrinsic excitability of prelimbic neurons.•Systemic LPS dysregulates the action potential kinetics and firing output.•Systemic LPS decreases the afterhyperpolarization current. |
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ISSN: | 0161-813X 1872-9711 |
DOI: | 10.1016/j.neuro.2022.05.010 |