Electrophysiological correlates of familiarity in recognition memory and exclusion tasks.

ERPs were acquired in the test phases of three memory experiments, where three classes of word were presented. These were: (i) words encountered in a prior study phase (studied words), (ii) words presented at test for the first time (new words), and (iii) new words repeated after a lag of 7-9 intervening words (repeated test words). In experiments 1 and 2, participants were asked to respond on one key to studied words and on another to new as well as to repeated test words. In experiment 3, a binary response was again required, but in this case repeated test and studied words were assigned to the same key. In each experiment, the principal focus for analysis was on the differences between the ERPs at mid-frontal electrode locations from 300 to 500 ms post-stimulus that were associated with incorrect responses to studied words (misses) and correct responses to new words. It has been proposed that relatively greater positivity for studied than for new words at this locus reflects the greater familiarity of studied than of unstudied words. ERPs elicited by misses were reliably more positive-going than those elicited by correct rejections in experiments 1 and 2 only. These findings support the link between this modulation of the electrical record and familiarity in so far as the designs of the experiments lead to the prediction that the average level of familiarity associated with misses should be higher in the first two experiments than in the third. In combination with findings in other studies, these data support dual-process accounts of recognition memory.

Indexing strategic retrieval of colour information with event-related potentials.

Event-related potentials (ERPs) were acquired during two experiments in order to determine boundary conditions for when recollection of colour information can be controlled strategically. In initial encoding phases, participants saw an equal number of words presented in red or green. In subsequent retrieval phases, all words were shown in white. Participants were asked to endorse old words that had been shown at encoding in one colour (targets), and to reject new test words as well as old words shown in the alternate colour (non-targets). Study and test lists were longer in Experiment 1, and as a result, the accuracy of memory judgments was superior in Experiment 2. The left-parietal ERP old/new effect--the electrophysiological signature of recollection--was reliable for targets in both experiments, and reliable for non-targets in Experiment 1 only. These findings are consistent with the view that participants were able to restrict recollection to targets in Experiment 2, while recollecting information about targets as well as non-targets in Experiment 1. The fact that this selective strategy was implemented in Experiment 2 despite the close correspondence between the kinds of information associated with targets and non-targets indicates that participants were able to exert considerable control over the conditions under which recollection of task-relevant information occurred.

Cellular stress in xenopus kidney cells enhances the phosphorylation of eukaryotic translation initiation factor (eIF)4E and the association of eIF4F with poly(A)-binding protein.

Eukaryotic initiation factor (eIF) 4E binds to the 5'-cap structure of eukaryotic mRNA and has a central role in the control of cell proliferation. We have shown previously that the stimulation of cultured Xenopus kidney cells with serum resulted in the activation of protein synthesis, enhanced phosphorylation of eIF4E and increased binding of the adapter protein, eIF4G, and poly(A)-binding protein (PABP) to eIF4E to form the functional initiation factor complex, eIF4F/PABP. We now show that cellular stresses such as arsenite, anisomycin and heat shock also result in increased phosphorylation of eIF4E, eIF4F complex formation and the association of PABP with eIF4G, in conditions under which the rate of protein synthesis is severely inhibited. In contrast with reported effects on mammalian cells, the stress-induced increase in eIF4F complex formation occurs in the absence of changes in the association of eIF4E with its binding proteins 4E-BP1 or 4E-BP2. The stress-induced changes in eIF4E phosphorylation were totally abrogated by the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580, and were partly inhibited by the phosphoinositide 3-kinase inhibitor LY294002 and the mammalian target of rapamycin (mTOR) inhibitor rapamycin. However, eIF4E phosphorylation was unaffected by extracellular signal-regulated protein kinase (MAP kinase) inhibitor PD98059. These results indicate that cellular stresses activate multiple signalling pathways that converge at the level of eIF4F complex formation to influence the interactions between eIF4E, eIF4G and PABP.

The association of initiation factor 4F with poly(A)-binding protein is enhanced in serum-stimulated Xenopus kidney cells.

Serum stimulation of cultured Xenopus kidney cells results in enhanced phosphorylation of the translational initiation factor (eIF) 4E and promotes a 2.8-fold increase in the binding of the adapter protein eIF4G to eIF4E, to form the functional initiation factor complex eIF4F. Here we demonstrate the serum-stimulated co-isolation of the poly(A)-binding protein (PABP) with the eIF4F complex. This apparent interaction of PABP with eIF4F suggests that a mechanism shown to be important in the control of translation in the yeast Saccharomyces cerevisiae also operates in vertebrate cells. We also present evidence that the signaling pathways modulating eIF4E phosphorylation and function in Xenopus kidney cells differ from those in several mammalian cell types studied previously. Experiments with the immunosuppressant rapamycin suggest that the mTOR signaling pathway is involved in serum-promoted eIF4E phosphorylation and association with eIF4G. Moreover, we could find little evidence for regulation of eIF4E function via interaction with the specific binding proteins 4E-BP1 or 4E-BP2 in these cells. Although rapamycin abrogated serum-enhanced rates of protein synthesis and the interaction of eIF4G with eIF4E, it did not prevent the increase in association of eIF4G with PABP. This suggests that serum stimulates the interaction between eIF4G and PABP by a distinct mechanism that is independent of both the mTOR pathway and the enhanced association of eIF4G with eIF4E.