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

Abstract

The effects of membrane-permeant Ca2+ chelators on field EPSPs (fEPSPs) were measured in the hippocampal CA1 region of brain slices from young (24 months) 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 but enhanced fEPSPs in aged slices. BAPTA derivatives with calcium dissociation constants (K(d)) of 0.2-3.5 μM reduced or enhanced fEPSPs in young and aged slices, respectively, but 5',5'-dinitro BAPTA-AM (K(d) of ~7000 μM) had no effect. Frequency facilitation of the fEPSPs occurred in young, 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 slices were eliminated by perfusing with a low Ca2+-high Mg2+ saline or with the calcium blocker Co2+. These data suggest that intracellular Ca2+ regulation is altered and raised in aged neurons. Cell- permeant calcium buffers may be able to 'ameliorate' deficits in synaptic transmission in the aged brain.