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The Journal of Neuroscience, February 1, 1999, 19(3):906-915

Differential Modulation of Synaptic Transmission by Calcium Chelators in Young and Aged Hippocampal CA1 Neurons: Evidence for Altered Calcium Homeostasis in Aging

Aviv Ouanounou^{1, 2, 3, 4}, Liang Zhang^{1, 3}, Milton P. Charlton^{1, 2, 4}, and Peter L. Carlen^{1, 2, 3, 4}

¹ Playfair Neuroscience Unit, Toronto Hospital Research Institute, ² Medical Research Council Group on Nerve Cells and Synapses, and Departments of ³ Medicine (Neurology) and ⁴ Physiology, University of Toronto, Toronto, Ontario M5T 2S8, Canada

The effects of membrane-permeant Ca²⁺ chelators on field EPSPs (fEPSPs) were measured in the hippocampal CA1 region of brain slices from young (2-4 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.

Key words: calcium chelator; BAPTA-AM; EGTA-AM; probenecid; hippocampus; field EPSP; frequency facilitation; synaptic transmission; aging

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Copyright © 1999 Society for Neuroscience  0270-6474/99/193906-10$05.00/0

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