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 hippocampus-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 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.  Intracellular signaling pathways and alterations in calcium currents that may lead to these changes in intrinsic excitability during learning are being explored.