Bimodal effects of acetylcholine on synchronized calcium oscillation in rat cultured cortical neurons.

To understand the plastic changes in neural network dynamics, we analyzed the modulating effects of cholinergic agonists on synchronized Ca(2+) oscillation in the rat primary cultured cortical neurons. At 5-10 days after establishment of the culture, neurons exhibited synchronized Ca(2+) oscillation. This Ca(2+) oscillation was derived from glutamatergic and gamma-aminobutyric acid (GABA)ergic synaptic inputs from neighboring neurons. Application of acetylcholine and nicotine increased, decreased, or did not change the frequency of synchronized Ca(2+) oscillation, depending on the colonies in the culture. The presence of cholinergic neurons in the culture was confirmed by immunocytochemical staining. Our study provided evidence for the first time that cholinergic neurons exert excitatory influences on GABAergic neurons as well as glutamtergic neurons, resulting in bimodal effects on the frequency of synchronized Ca(2+) oscillation in the cortical neural network.