Brain Mechanisms for Altered Learning Capacity During Aging

Changes in neurons occuring during aging that cause age-related learning deficits are beginning to be understood.  We have studied these processes in hippocampus-dependent associative learning.  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 conditioning demonstrate functional alterations during learning and aging.  Mechanisms underlying these alterations in firing rate have been studied in brain slices.  These studies of alterations in the calcium-activated potassium currents that increase neuronal excitability during associative learning in young animals and cause learning impairments in 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 that may lead to these changes during learning are being explored.