UNSCHEDULED BRAIN DNA-SYNTHESIS, LONG-TERM POTENTIATION, AND DEPRESSION AT THE PERFORANT PATH-GRANULE CELL SYNAPSE IN THE RAT

We investigated the effect of long-term potentiation (LTP) of the perf orant path-granule cell synapse, on the synthesis of DNA in the target area and in polysynaptically stimulated hippocampal (CA3/CA1) and cor tical areas (entorhinal, temporal, and occipital cortices) in the rat. The contralateral nonstimulated side was used as a control. The degre e of LTP was indexed by the field EPSP and population spike amplitude recorded in the dentate area of the stimulated side before and after h igh frequency stimulation (250 Hz, 250 ms) every 30 min. DNA synthesis was evaluated in tissue homogenates after a 3-h period of incorporati on of H-3-thymidine. DNA synthesis was significantly lower in the stim ulated side in the hippocampal cortex CA3/CA1 (-25%), and in the entor hinal cortex (-50%), but not in the dentate area. In addition, the occ urrence of preparations without expression of LTP allowed the analysis of unscheduled brain DNA synthesis (UBDS) in a supposedly long-term d epression (LTD) subgroup. UBDS was higher in the group without LTP (no -LTP group) than in that with a significant LTP expression (LTP-group) on both sides of the brain. Furthermore, correlative analyses reveale d that UBDS covaried with LTP of the EPSP (but not of population spike ) in the dentate area and in extratarget hippocampal subregions on bot h sides and in dorsal cortex on the stimulated side. Further, regional crosscorrelation analyses revealed a high degree of coupling among br ain sites following LTP. In conclusion, the evidence suggests that LTP was accompanied by a graded facilitation of DNA synthesis in the dent ate target area and in the dorsal cortex, and by a strong inhibition i n polysynaptically stimulated hippocampal cortex. The regional crossco rrelation analysis indicates the participation of the entire neural ne twork sampled. Altogether, the data lend further support to the hypoth esis that DNA synthesis is due to genomic remodeling, which might play a role in brain information processing and storage.