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Ionic Zn 2+ has increasingly been recognized as an important neurotransmitter and signaling ion in glutamatergic neuron pathways. Intracellular Zn 2+ transiently increases as a result of neuronal excitation, and this Zn 2+ signal is essential for neuron plasticity, but the source and regulation of the signal is still unclear. In this study, we rigorously quantified Zn 2+ , Ca 2+ , and pH dynamics in dissociated mouse hippocampal neurons stimulated with bath application of high KCl or glutamate. While both stimulation methods yielded Zn 2+ signals, Ca 2+ influx, and acidification, glutamate stimulation induced more sustained high intracellular Ca 2+ and a larger increase in intracellular Zn 2+ . However, the stimulation-induced pH change was similar between conditions, indicating that a different cellular change is responsible for the stimulation-dependent difference in Zn 2+ signal. This work provides the first robust quantification of Zn 2+ dynamics in neurons using different methods of stimulation.

Dissociated Hippocampal Neurons Exhibit Distinct Zn2+ Dynamics in a Stimulation-Method-Dependent Manner

Dissociated Hippocampal Neurons Exhibit Distinct Zn²⁺ Dynamics in a Stimulation-Method-Dependent Manner