Intracellular calcium stores contribute to increased susceptibility to LTD induction during aging

Release of Ca2+ from intracellular Ca2+ stores (ICS) is involved in age-related changes in the induction of long-term potentiation. However, the role of this Ca2+ source for the increased susceptibility to long-term depression (LTD) with advanced age is unknown. Extracellular excitatory postsynaptic field potentials were recorded from CA3-CA1 synaptic contacts from hippocampal slices obtained from young (5-8 months) and aged (22-24 months) male Fischer 344 rats. Blockade of Ca2+-release from ICS by cyclopiazonic acid, thapsigargin, or ryanodine blocked LTD induction in aged rats. Impaired LTD was not simply due to a loss of a Ca2+ source. The idea that ICS may play prominent role in regulating synaptic modifiability through regulation of cell excitability and the timing of pre and postsynaptic activity is discussed.