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Neuroscience
Cluster Scientific Retreat |
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Dept of Physiology, Northwestern Mechanisms of associative learning in young and aging brain The neuronal alterations which occur in important neuron populations in young adult animals and changes in those processes which occur during aging and cause age-related learning deficits are beginning to be understood with cellular to systems level analyses. We have studied these processes with hippocampally-dependent trace eyeblink conditioning tasks. Calcium and calcium-activated potassium currents, that help control intrinsic neuronal excitability and are altered during learning and in aging, have been extensively studied. In vivo recording studies of CA1 hippocampal pyramidal neurons during and after associative eyeblink conditioning demonstrate functional alterations during learning and aging. We have examined mechanisms underlying these alterations in firing rate by examining CA1 neurons in brain slices. These current and voltage clamp studies of alterations in the slow calcium-activated potassium currents that increase neuronal excitability during associative learning in young animals and age-associated changes in these currents that occur in learning-impaired aging animals will be described. Behavioral pharmacological studies have demonstrated that age-associated behavioral changes can be reversed by compounds targeting neuronal excitability. The development of compounds acting at the calcium mediated potassium channel underlying the slow afterhyperpolarization may be a useful strategy for designing drugs to treat age-associated learning deficits and/or Alzheimer's Disease. Disterhoft, J.F. and Oh, M.M. Learning, Aging and Intrinsic Neuronal Plasticity. Trends in Neuroscience, 2006, 29, 587-599. Matthews, E., Weible, A.P., Shah, S., Disterhoft J.F. The BK-mediated fAHP is modulated by learning a hippocampus-dependent task. PNAS, 2008, 105, 15154-15159. Oh, M.M.,
McKay, B.M., Power, J.M. and Disterhoft, J.F. Learning-related postburst afterhyperpolarization reduction in CA1
pyramidal neurons is mediated by protein kinase A. PNAS, 2009, 106,
1620-1625. Matthews, E., Linardakis, J.M. and Disterhoft, J.F. The fast AHP and the slow AHP are differentially modulated in hippocampal neurons by aging and by learning. J. Neuroscience, 2009, 29, 4750-4755. 08/14/2009 |