One of the unfortunate but fundamental features of aging is the decline of recent memory, that is, the retention of newly acquired information. In order to understand this age-related memory loss, Dr. de Toledo-Morrell and her colleagues are carefully examining which types of memory decline with age, and studying how structural changes in individual synapses may contribute to senile (and possibly pre-senile) dementia. Dr. de Toledo-Morrell has chosen an animal model of age-related memory dysfunction, recently identified in the Fischer 344 rat. Two-thirds of the members of this rat strain will spontaneously develop an impairment in spatial memory as they age. As is seen in the human amnesias, this rodent memory loss is also associated with a disturbance in the function of the hippocampal formation of the brain. Since not all members of this strain develop the memory impairment, the individual differences provide an excellent model for investigating the synaptic substrates of normal memory, and of its decline. This research project combines behavioral, electrophysiological and quantitative electron microscopic techniques to examine the neurobiological basis of the age-related memory deficit. In addition, Dr. de Toledo-Morrell is providing a detailed analysis of the effects of pentoxifylline (found to reverse the age- associated memory loss in some species) on the electro- physiological and morphological characteristics of hippocampal synaptic plasticity.
