IMPAIRED FREQUENCY POTENTIATION AS A BASIS FOR AGING-DEPENDENT MEMORYIMPAIRMENT - THE ROLE OF EXCESS CALCIUM INFLUX

Frequency potentiation (FP), the growth of synaptic responses during r epetitive synaptic activation, has been found consistently to be impai red in hippocampus of aged rats. This impairment has also been found t o be correlated with aging-impaired learning/memory processes. Quantit ative ultrastructural analyses indicate that reduced synaptic vesicle attachment to active release zones, rather than vesicle depletion, is associated with impaired FP. Postsynaptic factors such as an increased afterhyperpolarization also appear to be involved. Excess calcium inf lux impairs FP (in contrast to its enhancing effect on long-term poten tiation), and an extensive series of studies has indicated that elevat ed voltage-dependent calcium influx occurs in hippocampal pyramidal ne urons of aged animals. Intracellular voltage recordings and voltage-cl amp analyses indicate that dihydropyridine-sensitive (L-type) calcium channels, and perhaps N-type channels, are altered by aging, thereby r esulting in impaired function (and possibly, in gradual neurodegenerat ion).