Action potential throughput in aged rat hippocampal neurons: Regulation by selective forms of hyperpolarization

At hippocampal synapses, repetitive synaptic stimulation (RSS) in the theta frequency range (3–12 Hz) is associated with robust EPSP frequency facilitation (FF) and consequently, enhanced action potential (spike) generation and throughput. A complex, synaptically induced hyperpolarization (SIHP) is also triggered by synaptic activation, and a Ca2+-dependent afterhyperpolarization (AHP) is triggered above spike threshold. With aging, the AHP is increased and impairs intracellular spike generation, at least in accommodation protocols. However, little is known about how these aging changes interact to affect spike generation at physiological frequencies of RSS, or if the SIHP also is modified in aging. Here we performed the first tests of the net impact of these excitatory and inhibitory aging changes on spike generation during RSS. We report that during RSS at spike threshold (1) spike throughput is well sustained at theta frequencies in young and aged neurons; (2) an interposed AHP dampens spike generation, particularly in aged neurons and at higher frequencies; (3) compared to the AHP, the SIHP does not exert an equivalent inhibitory effect on spike throughput; and (4) in contrast to the AHP, the SIHP is reduced with aging. Together, these results are consistent with a model in which the source of the hyperpolarization is important in determining hippocampal spike throughput within the theta frequency range.