Protein Synthesis during Learning

Hyden and Lange (1) have reported that rats trained on the reversal of handedness exhibit increased protein synthesis in pyramidal neurons of the hippocampus. Their data, however, left the validity of this biochemical finding unresolved, for reasons discussed below. In particular, differences in the 3H-leucine concentrations suggest that the apparent increase in protein synthesis was an artifact, and that the only clear biochemical effect was the difference in the 3H-leucine concentration. Furthermore, even if these biochemical findings can be rigorously established, the behavioral conditions and meaning of the study were not adequately considered. 1 ) The 3H-leucine concentration (for which the units of measurement should be given) is of central importance to the results, since the apparent increase in protein synthesis only becomes manifest when the nondiffering uncorrected specific activities are converted to corrected specific activities by dividing by the 3H-leucine concentration. Although not pointed out in the study, the experimental 3H-leucine concentration (Table 1 ) was only one-half that of the control, a difference which is clearly significant. This raises two issues. First, if the difference occurred because greater amounts of protein were present in the experimental tissues as compared to the control, then the concentrations might represent a spurious indication of the tissue content of 3Hleucine, thereby invalidating the corrected specific activities. Presentation of data on the tritium and protein content of portions (100 ,ug) of hippocampal tissue might resolve this point. Second, if the difference in 31H-leucine concentrations arose -as a function of the 30-minute training period, then the 30-minute 3H-leucine concentration measured in the experimental rats would underestimate the total 3H-leucine available during the 30 minutes, and the corrected specific activity would therefore overestimate the amount of protein synthesis. This could account for the entire apparent difference in protein synthesis. Additional data on experimental and control 3Hleucine concentrations at 0, 15, and 30 minutes would permit the use of temporal integrations of 3H-leucine concentrations as the basis for corrections. 2) Apart from the above issue, the