Androgen Receptors and Hippocampal Function

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9604723 Handa The hippocampus is a forebrain structure of the temporal lobe, constituting an important part of the limbic system and of the Papez's circuit. Its general anatomy and connections to other regions of the brain are well defined. Functions that depend upon the hippocampus are recognition of novelty, learning and memory. Indeed it is believed that this brain region serves as a spatial map that helps us remember where we have been. Recently, it has been shown that the hippocampus contains a high concentration of androgen receptors suggesting that testosterone may influence this region of the brain. Moreover, sex differences in cognitive functions have been reported. Despite recent data demonstrating that the hippocampus is a major target for androgen and there are male-female differences in spatial memory and in learning, few studies have examined the neural mechanisms by which androgen can alter hippocampal function or hippocampal cell parameters. Recently, Dr. Handa showed that androgens influence hippocampal function by altering the n-methyl-d-aspartate (NMDA) receptors, which are important for glutamate neurotransmission and the underlying sensitivity to neurotoxic insults such as anoxia and chronic stress. He will now combine his expertise in molecular and cellular neuroendocrinology with Dr. Beck's talents in neurophysiology to carry out an integrative series of studies to examine the effects of androgen on hippocampal synaptic plasticity. They will examine the effects of androgen on hippocampal cell morphology, NMDA receptor composition and function, and enzyme activity. The results from these studies will provide new knowledge on the role that steroid hormones play in modulating a brain region that occupies a central role in regulating multiple non- reproductive behaviors.