Neuroendocrine modulation of LTP durability

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This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).Hormonal responses to an experience can gate how well and for how long the experience is remembered. Epinephrine (adrenaline) is one such hormonal regulator of memory strength and durability. Recent findings by the PI, using an electrophysiological model of memory called long-term potentiation (LTP), demonstrate that epinephrine also modulates the strength and durability of connections between neurons known as synapses in brain areas involved in memory in rats. Specifically, an injection of epinephrine extends LTP durability from minutes, seen without epinephrine, to days. This proposal examines the neural sites and molecular mechanisms important to this conversion of short- to long-lasting LTP by epinephrine. Aim 1 will test actions at two brain regions, the hippocampus and amygdala, important in memory formation. Epinephrine likely modulates LTP strength and durability indirectly via specific receptors in the amygdala and directly influences LTP strength through receptors in the hippocampus, the site of change in synaptic strength. Aim 2 will examine molecular events involved in the conversion to long lasting synaptic strength, focusing on the activation of one protein, CREB, that regulates the expression of many genes. Predictions are that increases in CREB activity will correspond to increased durability of synaptic strength. Results from these studies will lend insight into how stress hormones, a component of strong emotions, lead to strong memories. The scientific impact of these experiments is potentially broad with findings that will advance knowledge in fields of mechanisms of memory, neuroendocrinology, and neurophysiology, extending basic findings to fields of learning, reproduction, and animal behavior. This project will provide extensive, unique research experiences for undergraduate and high-school students, with progress assessed by PIs and students using portfolios of written, technical, and subjective reports. Together with the varied outreach programs the PIs conduct, these opportunities will impact a wide and diverse group of prospective scientists.