The goal of this project is to identify the neural mechanisms involved in the well-established link between dietary iron deficiency (ID) and developmental impairments in learning and cognition. The hippocampus is the most important learning and memory structure in the mammalian brain. The hippocampus is critical for learning tasks that require the association of complex sets of information, and in humans it is critical for cognitive performance. Numerous studies in animals have shown that the hippocampus is more susceptible to ID during early development compared to other brain regions. An extensive list of animal and human studies has shown that ID impairs the development of learning and cognitive ability, and some of these studies suggest that these learning impairments persist well into adulthood. Together these lines of evidence strongly suggest that dietary ID alters the development of the hippocampus, and these alterations in turn significantly impact the development of children's cognitive and learning ability. Very little is known about how the functional physiology of the hippocampus is affected by ID during development. Experiment 1 in this proposal will determine if ID in postnatal developing rats impairs hippocampal synaptic responsiveness. This experiment will also determine if these physiological impairments are related to deficits in hippocampus-dependent learning. The animal learning paradigm that will be used in all of the experiments in this proposal combines trace and contextual fear conditioning, both of which have been shown to be dependent on the hippocampus. Our preliminary data demonstrate that ID in developing postnatal rats impairs learning in both of these hippocampus-dependent tasks. Our previous studies in normal adult animals have shown that single neurons in the hippocampus exhibit learning-specific encoding of the trace interval duration. Experiment 2 in this proposal will determine if ID in postnatal developing rats impairs hippocampal single neuron encoding of the trace interval duration during trace fear conditioning. Experiment 3 will determine if ID during postnatal development produces long-term impairments in hippocampal neurogenesis and hippocampus-dependent learning in young adult rats.
McEchron, Matthew D; Alexander, Danielle N; Gilmartin, Marieke R et al. (2008) Perinatal nutritional iron deficiency impairs hippocampus-dependent trace eyeblink conditioning in rats. Dev Neurosci 30:243-54 |
McEchron, Matthew D; Paronish, Michael D (2005) Perinatal nutritional iron deficiency reduces hippocampal synaptic transmission but does not impair short- or long-term synaptic plasticity. Nutr Neurosci 8:277-85 |
McEchron, Matthew D; Cheng, Alex Y; Liu, Heng et al. (2005) Perinatal nutritional iron deficiency permanently impairs hippocampus-dependent trace fear conditioning in rats. Nutr Neurosci 8:195-206 |