| We designed a model of early iron deficiency (ID) in the rodent that mimicked human conditions of fetal/early postnatal ID and assessed hippocampal dendritic growth and electrophysiological function both during the period of ID (P15, P30) and following iron rehabilitation (P65). In our models of early ID, the hippocampus demonstrated a greater percentage of iron concentration loss than the total brain at P15, suggesting increased hippocampal vulnerability during this developmental period. Qualitative and quantitative immunohistochemical analyses of dendritic structure and growth demonstrated iron deficient pups to display truncated apical dendritic morphology in CA1 at P15 and a persistence of an immature apical dendritic pattern at P65. We then assessed hippocampal function and plasticity by investigating basal synaptic transmission, paired-pulse facilitation (PPF), and long-term potentiation (LTP) at Schaffer collateral-CA1 synapses. While the iron sufficient control pups demonstrated an increase in synaptic strength across development, iron deficient pups demonstrated no developmental increase in either basal synaptic function or PPF between P15 and P65. Furthermore, repletion of iron status did not produce significant changes in the formerly iron deficient group's developmental trajectory indicating long-term or permanent changes within the mechanisms producing these electrophysiological responses. Expression of LTP, an established biological substrate of learning and memory, from iron deficient pups did not differ from iron sufficient pups at P15, but iron deficient slices failed to demonstrate a decrease in LTP expression from P15 to P30. After iron repletion, LTP expression was lower in the iron deficient group at P65. Thus, early ID delays and/or abolishes the developmental maturation of structural and electrophysiological components of synaptic efficacy and plasticity. |
