Evidence that High Frequency Stimulation Influences the Phosphorylation of Pyruvate Dehydrogenase and that the Activity of this Enzyme is Linked to Mitochondrial Calcium Sequestration

Abstract

Publisher Summary The hippocampal slice contains the major afferent input and the trisynaptic circuitry characteristic of the hippocampus. Approximately 1 hour after preparation of the slice, a bipolar stimulating electrode is placed where it activates the massive Schaffer-commissural input to the CA- 1 pyramidal cells. A recording electrode is placed in the terminal field of these axons where it can record the extracellular representation of the EPSP produced when the Schaffer-commissural axons are stimulated. Single pulses are then delivered until a stable baseline response is obtained and held for 30 min. Then a 1 sec burst of high frequency (100 pulses sec--1) stimulation is delivered for 1 sec and then testing is resumed with stimulation at 1 pulse sec-'. A short-term form of potentiation (STP) can be detected within seconds of the cessation of the high frequency stimulation; and, like the post-tetanic potentiation seen at the neuromuscular junction, this STP decays rapidly. However, the potentiated response does not return to baseline. Rather, within 2–3min of the cessation of stimulation, the potentiated response is stabilized and this potentiated response typically persists for the life of the slice. This chapter describes experimental evidence that have lead to the conclusion that high-frequency stimulation influences the phosphorylation of pyruvate dehydrogenase and that the activity of this enzyme is linked to mitochondrial calcium sequestration.