CORRELATIONS BETWEEN IMMEDIATE-EARLY GENE INDUCTION AND THE PERSISTENCE OF LONG-TERM POTENTIATION

The duration of long-term potentiation in the dentate gyrus of awake r ats was examined following systematic manipulation of the number of st imulus trains delivered. This was correlated with the induction of imm ediate early genes in separate groups of animals given identical stimu lus regimes. Following 10 trains of stimulation, long-term potentiatio n decayed with a time constant of up to several days (long-term potent iation 2), and this correlated with the appearance of an increase in t he messenger RNA and protein levels of zif/268. Increasing the number of stimulus trains resulted in a greater probability of eliciting long -term potentiation with a time constant of several weeks (long-term po tentiation 3), as well as increasing the induction of zif/268, c-Jun, Jun-B. Jun-D and Fos-related proteins. When 10 trains were delivered r epeatedly on up to five consecutive days, only the zif/268 protein lev els showed associated changes. These data provide support for the hypo thesis that long-term potentiation 3 involves mechanisms additional to those for long-term potentiation 2. One possible mechanism is altered gene expression, initiated by immediate early gene transcription fact ors such as zif/268 and possibly homo- or heterodimers of Fos and Jun family members, that then contributes to the stabilization or maintena nce of long-term potentiation 3.