Wc. Abraham et al., IMMEDIATE-EARLY GENE-EXPRESSION ASSOCIATED WITH THE PERSISTENCE OF HETEROSYNAPTIC LONG-TERM DEPRESSION IN THE HIPPOCAMPUS, Proceedings of the National Academy of Sciences of the United Statesof America, 91(21), 1994, pp. 10049-10053
Long-term depression (LTD) of synaptic efficacy is likely to be as imp
ortant in memory processing as the more well-known long-term potentiat
ion (LTP). The case for LTD serving as a memory mechanism, however, re
quires that it be shown to persist across days or weeks at least. Here
we examined the persistence of heterosynaptic LTD in the medial and l
ateral perforant path inputs to the dentate gyrus in awake rats and co
rrelated this persistence with the degree of immediate early gene expr
ession as assessed immunohistochemically. Rats were chronically implan
ted with separate stimulating electrodes in the medial and lateral per
forant paths and an extracellular field potential recording electrode
in the dentate hilus. After recovery from surgery, either the medial o
r the lateral perforant path was tetanized with 400-Hz trains, and hom
osynaptic LTP and heterosynaptic LTD were followed across time. Hetero
synaptic LTD was shown to occur readily in awake animals and to persis
t across days or weeks, depending on the stimulation protocol. The per
sistence of LTD and LTP was highly correlated within animals. Addition
al animals, given the same tetanization protocols, showed that the gre
atest immediate early gene expression occurred following that protocol
which consistently gave the longest lasting LTP and LTD. These data s
upport the proposed role of LTD in memory processing but question whet
her immediate early genes are important for the persistence of LTP, LT
D, or both.