Brain and Cognition Division

We examine changes in neural mechanisms of learning and memory under various hormonal states and across the lifespan. To understand neural plasticity we use multiple levels of analysis -- from behavior to neural system to cell.

Our work focuses on the regulation of learning and memory by ovarian hormones. One goal is to understand the molecular and cellular processes underlying cognitive aging, especially in females undergoing reproductive senescence. We recently initiated a series of experiments testing the role of exercise and fitness in healthy and pathological aging.

As organisms age, changes in brain and cognitive function may be regulated by concomitant changes in circulating hormones. For example, as women transition through menopause, decreased performance on verbal declarative memory tasks accompanies the decline in ovarian hormone levels. In rodents, we have found that estradiol, the most potent estrogen in mammals, acts at different brain sites to enhance some cognitive functions but to impair others. Some brain targets of estradiol lack classic estrogen receptors. Thus, one set of current projects examines the roles of estradiol activation through non-traditional, novel estrogen receptor subtypes in modulating the participation of different memory systems in learning and memory.

Because of the widely held belief that information storage in the brain results from changes in synaptic strength, a related line of research in our lab examines synaptic models of memory and forgetting across the lifespan. Using standard neurophysiological models of long-term potentiation (LTP) and long-term depression (LTD) of synaptic strength, our lab tests the possibility that forgetting reflects an active mechanism involving synaptic plasticity. These experiments include studies of hormonal, cell and molecular regulation of LTP and LTD induction and maintenance in young, middle aged and old rats.

As mentioned, the techniques we use span many levels of analysis including tests of learning and memory, neuropharmacology, in vivo electrophysiology, light microscopy, and several biochemical techniques (quantitative Westerns, immunocytochemistry, ELISAs, RIAs, HPLC) for signal transduction molecules and transcription factors (CREB, pCREB), immediate early genes (cFos), trophic factors (BDNF), and neurotransmitters (ACh).

Representative Publications:

• Korol, D.L. and Gold, P.E. (2008). Epinephrine converts LTP from transient to durable form in awake rats. Hippocampus, 18, 81-91.
• Zurkovsky, L., Brown, S.L., Boyd, S.E., Fell, J.A., and Korol, D.L. (2007). Estrogen modulates learning in female rats by acting directly at distinct memory systems. Neuroscience, 144, 26-37.
• Zurkovsky, L., Brown, S.L., and Korol, D.L. (2006). Estrogen enhances place learning through estrogen receptors in the hippocampus. Neurobiology of Learning and Memory, 86, 336-343.
• McElroy, M.W. and Korol, D.L. (2005). Intrahippocampal administration of muscimol shifts learning strategy in gonadally intact young adult female rats. Learning and Memory, 12, 150-158.
• Korol, D.L. (2004). Role of estrogen in balancing contributions from multiple memory systems. Neurobiology of Learning and Memory, 82, 309-323.

Classes Recently Taught:

• Neurobiology of Aging
• Exercise and Brain Function
• Seminars on Synaptic Plasticity, Cellular and Molecular Mechanisms of Memory, Hormones and Behavior, Aging