Differential modulation of synaptic transmission by calcium chelators in young and aged hippocampal CA1 neurons: Evidence for altered calcium homeostasis in aging

The effects of membrane-permeant Ca2+ chelators on field EPSPs (fEPSPs) wer e measured in the hippocampal CA1 region of brain slices from young (2-4 mo nths) and old (24-27 months) Fischer 344 rats. BAPTA-AM depressed fEPSPs in young slices by up to 70% but enhanced fEPSPs by 30% in aged slices. EGTA- AM, with slower binding kinetics, did not affect fEPSPs from young slices b ut enhanced fEPSPs in aged slices. BAPTA derivatives with calcium dissociat ion constants (K-d) of 0.2-3.5 mu M reduced or enhanced fEPSPs in young and aged slices, respectively but 5',5'-dinitro BAPTA-AM (K-d of similar to 70 00 mu M) had no effect. Frequency facilitation of the fEPSPs occurred in yo ung, but not in aged, slices, except when BAPTA-AM or EGTA-AM was perfused onto aged slices. The differential effects of BAPTA-AM in young and old sli ces were eliminated by perfusing with a low Ca2+-high Mg2+ saline or with t he calcium blocker Co2+. These data suggest that intracellular Ca2+ regulat ion is altered and raised in aged neurons. Cell-permeant calcium buffers ma y be able to "ameliorate" deficits in synaptic transmission in the aged bra in.