RAT hippocampal slices were used to evaluate the effects of glucose de
privation and the ability of lactate or pyruvate to preserve histologi
cal integrity and synaptic function. Dark cell changes were observed d
uring 180 min incubations in glucose-free solutions. These changes wer
e blocked by substituting 10 mM lactate or pyruvate for glucose during
the incubation. Excitatory postsynaptic potentials disappeared during
60 min of glucose deprivation but were restored by subsequent introdu
ction of glucose, lactate or pyruvate. Incubation of slices with iodoa
cetate revealed a distinct pattern of damage that was blocked complete
ly by pyruvate and partially by lactate. These results indicate that e
xogenous pyruvate and lactate can serve as energy substrates in the hi
ppocampus when glucose is unavailable or glycolytic metabolism is impa
ired.