Activity pattern in excitatory and inhibitory network of iPS cell-derived neurons

Abstract

It is important to know how spontaneous activity patterns of neuronal network are modulated by alteration in ratio and connections between excitatory (glutamatergic) and inhibitory (GABAergic) neurons in order to elucidate the contribution of GABA-mediated inhibition to maintenance of cortical function. Our purpose is to construct neuronal networks with various excitatory/inhibitory conditions in vitro using induced pluripotent stem (iPS) cell, and to analyze activity patterns of neuronal network. First, mouse iPS cells were induced to differentiate into excitatory or inhibitory neurons selectively. Second, these neurons were cultured on a microelectrode array under several network conditions, and neuronal activity was recorded. As a result, spontaneous network activities of iPS cell-derived neurons were observed, and pharmacological experiments indicated that the activities depended on strength and amounts of excitatory and inhibitory synaptic transmissions. Moreover, neuronal oscillations with different frequencies and active-phase durations were observed when neuronal excitatory/inhibitory ratio and connections were altered.