Peter Morgane, Ph.D. - US grants

The proposed experiments are a comprehensive plan for determining how gestational malnutrition affects development and maintenance of neuronal plasticity in the hippocampal formation. Using our well established malnutrition model we are proposing to study the effects of prenatal protein deprivation on the ontogeny of two forms of electrophysiological plasticity: (1) long-term plasticity by measuring the establishment and maintenance of long-term potentiation (LTP) in the dentate gyrus and (2) short-term plasticity by measuring the effects of vigilance states on field potentials and recurrent inhibition in the dentate gyrus. LTP is a form of synaptic plasticity regarded as a putative substrate for learning and memory and is the simplest paradigm yet developed where use alone leads to an increase in synaptic efficacy that lasts for weeks or months. Our previous studies using anesthetized normal and prenatally malnourished rats revealed that prenatal malnutrition leads to a deficit in the ability to potentiate the synaptic component of LTP (population EPSP) but not the cell firing component (population spike). In our first series of experiments we plan to examine this finding in the chronically implanted, freely moving animal in order to study LTP over a longer time course in the awake preparation in terms of its development and maintenance. In our second series of studies on short-term, vigilance state-dependent plasticity in the dentate gyrus we will use the paired-pulse technique to simultaneously monitor the effect of sleep/waking state on field potentials and recurrent inhibition. In this regard, it has been well established that field potentials throughout the hippocampal trisynaptic circuit are vigilance state dependent. However, the role of hippocampal interneurons in these effects have been largely ignored. Our paired pulse experiments will provide new information on the local circuit mechanisms by which sleep- waking states exert their influence on field potentials in the dentate gyrus. These studies are thus expected to show how prenatal protein malnutrition may lead to alterations in the function of local circuit interneurons. Overall, these experiments will reveal how malnutrition may affect specific neuronal circuits in the hippocampus and how a prenatal stressor can affect neuronal plasticity in adulthood even when dietary rehabilitation is initiated at birth.