Iron deficiency (ID) is the most prevalent nutritional disorder in the world, and numerous reports suggest that ID during early development produces cognitive and motor impairments in children and adolescents. The present proposal will use rats to determine if perinatal ID impairs several forms of a motor learning task called eyeblink conditioning. One form of this task, called delay eyeblink conditioning, is administered by presenting an auditory conditioned stimulus (CS) and following it immediately by a periorbital unconditioned stimulus (US) which produces an eyeblink response. After repeated pairings of the CS and US, the CS will elicit a conditioned eyeblink response which precedes the US. This delay eyeblink conditioning task depends on circuits primarily through the cerebellum, a brain structure which is critical for motor coordination. If, however, a silent trace interval separates the CS and US the task is called trace eyeblink conditioning, and it depends on circuits through both the cerebellum and hippocampus. Delay and trace eyeblink conditioning can be useful tools for studying how perinatal ID affects cerebellar and hippocampal learning circuits. Our preliminary data show that rats subjected to perinatal ID are able to acquire cerebellum-dependent delay eyeblink conditioning, but they do so more slowly than control rats. These data also suggest that ID rats may show impairments in eyeblink response amplitude and timing. It is unknown if these impairments in the cerebellar task continue into adulthood after nutritional ID has been reversed.
Specific Aim I will determine if perinatal ID produces irreversible impairments in cerebellum-dependent delay eyeblink conditioning which persist into adulthood after iron diets are returned to normal. A previous study from our laboratory used a much different non-motor fear conditioning task to show that perinatal ID completely prevents hippocampus-dependent fear learning, and this impairment was not reversed by a normal iron diet.
Specific Aim II will determine if perinatal ID also produces complete and irreversible impairments in hippocampus-dependent motor learning (i.e., trace eyeblink conditioning). In lay terms, this proposal will help us understand the impact of iron nutrition on the development children's ability to learn fine motor skills. Moreover, eyeblink conditioning is often used in humans; therefore, this animal learning proposal could be critical for future eyeblink conditioning studies with ID in humans. ? ? ?
| 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 |
