Differential acute impact of therapeutically effective and overdose concentrations of lithium on human neuronal single cell and network function

Abstract Lithium salts are used as mood-balancing medication prescribed to patients suffering from neuropsychiatric disorders, such bipolar disorder and major depressive disorder. cross the blood-brain barrier reach brain parenchyma within few hours after oral application, however, how lithium influences directly human neuronal function is unknown. We applied patch–clamp microelectrode array technology on induced pluripotent stem cell (iPSC)-derived cortical neurons acutely exposed therapeutic (<1 mM) overdose concentrations (>1 of chloride (LiCl) assess therapeutically effective LiCl influence electrophysiological at synapse, single-cell, network level. describe that iPSC-cortical showed an increased activity under all tested concentrations. Furthermore, we reveal a lithium-induced, concentration-dependent, transition regular synchronous using concentration mM LiCl) epileptiform-like discharges LiCl). The lithium-induced was similar caused by GABA A -receptor antagonist. Patch–clamp recordings reduces action potential threshold concentrations, only causes frequency spontaneous AMPA-receptor mediated transmission. By applying antagonist anti-epileptic drug Perampanel, demonstrate Perampanel suppresses in neurons. provide insights single neuron, levels. evidence pathological