Brain RNA synthesis, long-term potentiation and depression at the perforant path-granule cell synapse in the guinea...

The effects of long-term changes in synaptic efficacy at the perforant path-granule cell synapse on the de-novo synthesis of ribonucleic acid (RNA) were investigated in hippocampal and cortical areas in anaesthetized Guinea pig preparations. Two experiments were run with stimulating and recording microelectrodes aimed at the perforant bundle and dentate 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) was delivered to the left perforant bundle with the contralateral side as control. In Experiment 2, animals received LFS or HFS trains with implanted nonstimulated animals used as controls. The latency and amplitude of the field postsynaptic potentials (FPSP) and population spike (POPS) were monitored under baseline conditions and following stimulation 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). In both experiments RNA synthesis was determined by measuring the amount of 3H-5,6-uridine incorporated into the RNA 3 h after bilateral intraventricular injection. In Exp. 1 the LFS group showed a higher synthesis of RNA than both HFS groups. The rate of RNA synthesis did not differ between the stimulated and nonstimulated side. In Exp. 2 the HFS groups showed a decreased RNA synthesis. In the HFS-F group, it pertained to the dorsal dentate area, CA1, subiculum, cingulate and dorsal cortices bilaterally, and to the ventral dentate area and CA3 on the nonstimulated side. In contrast, the HFS-S group showed decreased RNA synthesis at the dorsal dentate area and dorsal cortex on the stimulated side, and at CA1, subiculum, and cingulate cortex bilaterally. The decrease was stronger in the HFS-F than in the HFS-S group. Moreover, the 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 heterosynaptic sites. Further, correlative analyses between FPSP, POPS and RNA synthesis revealed a complex pattern, depending upon the type of stimulation and on the brain side. Finally, cross-correlation analyses revealed a high degree of coupling among brain sites in the stimulated groups, indicating distributed covariant changes in RNA synthesis across different brain sites. Thus, changes in synaptic efficacy covary with changes in RNA synthesis, and presumably exert a modulatory role on gene expression.