Hippocampal neurobiological mechanisms of age-related memory dysfunction

Studies are reviewed which indicate that hippocampal frequency potentiation (the growth of neural responses during repetitive synaptic stimulation) is impaired in aged rats, and that this impairment may be important in learning and memory deficits found in these aged animals. Intracellular recording and ultrastructural studies suggest that both hippocampal frequency potentiation and the age deficit in such potentiation are synaptic processes (probably presynaptic), and that the deficit may be due to an age-related increase in calcium influx during depolarization. The latter could in some way result from alterations in the function of a Ca-mediated inactivation of Ca current mechanism recently found in hippocampal neurons. Since major hippocampal changes occur with aging in both rodents and humans, it seems possible that these data are also relevant to human brain aging. Consequently, it is suggested that Alzheimer's disease results from an acceleration of normal age-related neuronal calcium conductance changes by some unknown process (e.g., viruses, aluminum, genetic factors, etc.), leading to a rapid deterioration of brain structure.