Single-Vesicle Electrochemistry Following Repetitive Stimulation Reveals a Mechanism for Plasticity Changes with Iron Deficiency

Deficiency of iron, the most abundant transition metal in the brain and important for neuronal activity, is known to affect synaptic plasticity, causing learning and memory deficits. How iron deficiency impacts plasticity by altering neurotransmission at the cellular level is not fully understood. We used electrochemical methods to study the effect of iron deficiency on plasticity with repetitive stimulation. We show that during iron deficiency, repetitive stimulation causes significant decrease in exocytotic release without changing vesicular content. This results in a lower fraction of release, opposite to the control group, upon repetitive stimulation. These changes were partially reversible by iron repletion. This finding suggests that iron deficiency has a negative effect on plasticity by decreasing the fraction of vesicular release in response to repetitive stimulation. This provides a putative mechanism for how iron deficiency modulates plasticity.