Live-imaging and characterization of estrogen-induced dendritic spines

Icahn School Of Medicine At Mount Sinai, New York NY

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Abstract

DESCRIPTION (provided by applicant): The mechanisms underlying adult neural plasticity are poorly understood. Estrogen has emerged as a potential candidate to mediate the brain's ability to learn and encode new memories throughout life. Estrogen has been shown to induce spinogenesis and synaptic potentiation in the hippocampus of both female and male rat, and in non-human primates. In addition, estrogen has been implicated in a wide variety of disorders in which neural plasticity is altered, such as Alzheimer's Disease, Parkinson's Disease, depression, and schizophrenia. Although estrogen-induced spinogenesis has been studied for decades, live imaging and characterization of the newly emerged spines has not yet been performed. Here, I propose to use a combination of two-photon imaging and electrophysiological recording in acute hippocampal slices of adult rat to examine the functional properties of these new spines. My main hypothesis is that estrogen induces more "youthful" morphological and electrophysiological profiles in the adult hippocampus, with highly plastic new spines and an increase in silent synapses;however, these changes are permissive in that in the absence of "stabilizing" stimulus such as induction of LTP, the new spines and synapses disappear. The proposed experiments will be important for both investigations of estrogen's functions in the adult CNS as well as the functions of spino- and synaptogenesis in the adult in general. PUBLIC HEALTH RELEVANCE: The brain's ability to learn and form new memories is impaired in many disorders, such as Alzheimer's Disease, Parkinson's Disease, depression, and schizophrenia. Estrogen has been shown to increase the number of synapses, the sites of communications between brain cells. Thus, a better understanding of the mechanisms of estrogen's actions holds great potential for far-reaching clinical applications.