Dopamine is one of the most important neurotransmitters in brain. Our previous studies have shown that dopamine treatment elevates the intracellular Zn²⁺ concentration ([Zn²⁺]_i) in PC12 cells and elicits autophagosome formation. We sought to further characterize the effects of dopamine-induced [Zn²⁺]_i elevation on neurotransmission in cultured cortical neurons. Neurons expressing the autophagosome marker GFP-LC3 were treated with dopamine (250 µM) to induce the formation of autophagosomes; TPEN, a Zn²⁺ chelator, was used to block the dopamine-induced [Zn²⁺]_i elevation to verify the correlation between [Zn²⁺]_i elevation and autophagosome formation. Our results showed a significant increase in the number of autophagosomes in neurons treated with dopamine; TPEN pretreatment inhibited this effect. In addition, dopamine treatment suppressed the synaptic transmission among neurons; blocking dopamine-induced [Zn²⁺]_i elevation with TPEN reversed the inhibition. These data suggest that dopamine regulates neuron transmission by modulating the [Zn²⁺]_i level; however, the mechanism how dopamine induces [Zn²⁺]_i elevation is not clear. We will use different inhibitors to characterize how dopamine modulate the [Zn²⁺]_i level to verify the importance of Zn²⁺ in neurotransmission.