Carbachol-Induced Long-Term Synaptic Depression Is Enhanced During Senescence at Hippocampal CA3–CA1 Synapses

Abstract

Dysregulation of the cholinergic transmitter system is a hallmark of Alzheimer's disease and contributes to an age-associated decline in memory performance. The current study examined the influence of carbachol, a cholinergic receptor agonist, on synaptic transmission over the course of aging. Extracellular excitatory postsynaptic field potentials were recorded from CA3–CA1 synapses in acute hippocampal slices obtained from young adult (5–8 mo) and aged (22–24 mo) male Fischer 344 rats. Bath application of carbachol elicited a transient depression of synaptic transmission, which was followed by a long-lasting depression (CCh-LTD) observed 90 min after carbachol cessation in both age groups. However, the magnitude of CCh-LTD was significantly larger in senescent animals and was attenuated by N-methyl-d-aspartate receptor blockade in aged animals. Blockade of L-type Ca2+ channels inhibited CCh-LTD to a greater extent in aged animals compared to young adults. Finally, the expression of CCh-LTD was dependent on protein synthesis. The results indicate that altered Ca2+ homeostasis or muscarinic activation of Ca2+ signaling contribute to the enhanced CCh-LTD during senescence.