NEUR 451 - Neurobio of Aging
Neural mechanisms of learning and memory across the lifespan
We focus on modulation of neural mechanisms involved in learning and memory under various hormonal states and across the lifespan. To understand neural plasticity, we cross multiple levels of analysis -- from behavior to neural system to cell.
An overarching goal is to examine the molecular and cellular processes that contribute to cognitive aging. Recent work emphasizes regulation of learning and memory by ovarian hormones in attempt to model neural changes accompanying menopause in women. We also examine how exercise alters neural plasticity in both males and females to promote healthy brain and cognitive aging and to protect against neurodegenerative diseases such as Parkinson's. Finally, we use a synaptic model of neural plasticity to examine how hormones modulate the durability of memory at times switching short term changes into very long lasting ones.
Estrogens shift learning strategy:
In rodents, we have found that estrogens act at different brain sites to enhance some cognitive functions and to impair others. Moreover, rats select different strategies for solving some tasks depending on circulating estrogen levels even during the natural estrous cycle. Because some brain targets of estrogen lack classic estrogen receptors, one current project examines the roles of estrogen activation at traditional and novel estrogen receptor subtypes in modulating the participation of different memory systems in learning and memory. These findings are driving our new experiments testing the enhancing and impairing effects of botanical estrogens, commonly found in natural supplements, on learning and memory.
Metamodulation through physical and cognitive activity:
Another line of work tests the mechanisms underlying learning and memory enhancements following regular physical activity. Moreover, we have exciting new results suggesting that cognitive activity also enhances subsequent cognitive function and may do so in a manner similar to physical activity. In fact, recent findings point to the role of cell signaling pathways involving BDNF and modulation of neuronal and glial metabolism in metamodulation related to both physical and cognitive activity.
Synaptic model of PTSD:
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, cellular, and molecular regulation of LTP and LTD induction and maintenance in young, middle aged and old rats.
Approaches and methods:
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 such as CREB and pCREB, immediate early genes, trophic factors, and neurotransmitters such as cFos, BDNF, acetylcholine.
Dr. Karyn Frick (UW-M) and I co-edited of a special issue on Memory Impairment and Disease in Neurobiology of Learning and Memory, 2011, Volume 96.
Dr. Barbara Hug (UIUC) and I collaborate on Project NEURON, an NIH-funded Science Education Partnership Award to develop inquiry-based high school science curricula focusing on cutting-edge research from UIUC neuroscientists.
As outreach coordinator for the NSP, I have several collaborative projects that involve public engagement. Please see the Public Engagement tab on the NSP site.
Neese, S.L., Bandara, S.B., Doerge, D.R., Helferich, W.G., Korol, D.L., and Schantz, S.L. (2012). Effects of multiple daily genistein treatments on delayed alternation and a differential reinforcement of low rates of responding task in middle-aged rats. Neurotoxicology and Teratology, in press.
Zurkovsky, L., *Serio, S.J., and Korol, D.L. (2011). Intrastriatal estradiol treatment impairs response learning within two hours of treatment. Hormones and Behavior, 60, 470-477.
Newman, L.A., Korol, D.L., and Gold, P.E. (2011). Lactate produced by glycogenolysis in astrocytes regulates memory processing. PLoS ONE, 6(12), e28427.
McLaughlin, K.J., Wilson, J.O., Harman, J. Wright, R.L., *Wieczorek, L.A., Gomez, J., Korol, D.L., and Conrad, C.D. (2010). Chronic 17?-estradiol or cholesterol prevents stress-induced hippocampal CA3 dendritic retraction in ovariectomized females: Possible correspondence between CA1 spine properties and spatial acquisition, Hippocampus, 20, 768-786.
Neese, S.L., Korol, D.L., Katzenellenbogen, J.A., and Schantz, S.L. (2010). Impact of estrogen receptor alpha and beta agonists on delayed alternation in middle-aged rats. Hormones and Behavior. 58, 878-890.
Neese, S.L., Wang, V.C., Doerge, D.R., Helferich, W.G., Korol, D.L., and Schantz, S.L. (2010). Impact of dietary genistein and aging on executive function in rats. Neurotoxicology and Teratology, 32, 200-211.
Dohanich, G.P., Korol, D.L., and Shors, T.J. (2009). Steroids and Cognition, In: D. Pfaff, A. Arnold, R. Rubin, S. Fahrbach, and A. Etgen (eds), Hormones, Brain and Behavior, 2nd edition, Academic Press, New York, NY, 539-576.
Erickson, K.I. and Korol, D.L. (2009). The effects of hormone replacement therapy on the brains of postmenopausal women: A review of human neuroimaging studies. In: W. J. Chodzko-Zajko, A.F. Kramer, and L. Poon (Eds), Enhancing Cognitive Functioning and Brain Plasticity, Human Kinetics, Champaign, IL. 133-158.
Korol, D.L. and Gold, P.E. (2008). Epinephrine converts LTP from transient to durable form in awake rats. Hippocampus 18, 81-91.
Korol, D.L. and Gold, P.E. (2007). Hormones and Behavior, In: R.P. Kesner and J.L. Martinez (eds), Neurobiology of Learning and Memory, 2nd Edition, Elsevier, New York, NY, 243-268.
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.
Korol, D.L. (2004). Role of estrogen in balancing contributions from multiple memory systems. Neurobiology of Learning and Memory 82, 309-323. Evaluated by Faculty of 1000: http://www.f1000biology.com/article/15464412/evaluation
* denotes undergraduate author