BRAIN-RNA SYNTHESIS, LONG-TERM POTENTIATION AND DEPRESSION AT THE PERFORANT PATH-GRANULE CELL SYNAPSE IN THE GUINEA-PIG

The effects of long-term changes in synaptic efficacy at the perforant path-granule cell synapse on the de-novo synthesis of ribonucleic aci d (RNA) were investigated in hippocampal and cortical areas in anaesth etized Guinea pig preparations. Two experiments were run with stimulat ing and recording microelectrodes aimed at the perforant bundle and de ntate gyrus hilus on both sides. In Experiment 1, a low-frequency (LFS ; 0.02 Hz, 3 h) or high-frequency stimulation (HFS; 400 Hz, 250 ms) wa s delivered to the left perforant bundle with the contralateral side a s control. In Experiment 2, animals received LFS or HFS trains with im planted nonstimulated animals used as controls. The latency and amplit ude of the field postsynaptic potentials (FPSP) and population spike ( POPS) were monitored under baseline conditions and following stimulati on over a 3 h period. In addition, two HFS groups were tested with few (HFS-F: every 15 min) or several test stimuli (HFS-S: every 3 min). I n both experiments RNA synthesis was determined by measuring the amoun t of H-3-5,6-uridine incorporated into the RNA 3 h after bilateral int raventricular injection. In Exp. 1 the LFS group showed a higher synth esis of RNA than both HFS groups. The rate of RNA synthesis did not di ffer between the stimulated and nonstimulated side. In Exp. 2 the HFS groups showed a decreased RNA synthesis. In the HFS-F group, it pertai ned to the dorsal dentate area, CA1, subiculum, cingulate and dorsal c ortices bilaterally, and to the ventral dentate area and CA3 on the no nstimulated side. In contrast, the HFS-S group showed decreased RNA sy nthesis at the dorsal dentate area and dorsal cortex on the stimulated side, and at CA1, subiculum, and cingulate cortex bilaterally. The de crease was stronger in the HFS-F than in the HFS-S group. Moreover, th e subgroup with a low (0-60%) and that with a high (61-240%) level of long-term potentiation of FPSP revealed lower and higher RNA synthesis , respectively, both in homosynaptic target areas, and in heterosynapt ic sites. Further, correlative analyses between FPSP, POPS and RNA syn thesis revealed a complex pattern, depending upon the type of stimulat ion and on the brain side. Finally, cross-correlation analyses reveale d a high degree of coupling among brain sites in the stimulated groups , indicating distributed covariant changes in RNA synthesis across dif ferent brain sites. Thus, changes in synaptic efficacy covary with cha nges in RNA synthesis, and presumably exert a modulatory role on gene expression.