Behavioral studies with amnesic patients and imaging studies with healthy adults have suggested that medial temporal lobe (MTL) structures known to be essential for long-term declarative memory (LTM) may also be involved in the maintenance of information in working memory (WM). To examine whether MTL structures are involved in WM maintenance for faces, and the nature of that involvement, WM and LTM for faces were examined in normal participants via functional magnetic resonance imaging (fMRI) and in amnesic patients behaviorally. In Experiment 1, participants were scanned while performing a WM task in which they determined if two novel faces, presented 7 s apart, were the same or different. Later, participants' LTM for the faces they saw during the WM task was measured in an unexpected recognition test. During WM maintenance, the hippocampus was activated bilaterally, and there was greater activation during maintenance for faces that were later remembered than faces later forgotten. A conjunction analysis revealed overlap in hippocampal activations across WM maintenance and LTM contrasts, which suggested that the same regions were recruited for WM maintenance and LTM encoding. In Experiment 2, amnesic and control participants were tested on similar WM and LTM tasks. Amnesic patients, as a group, had intact performance with a 1-s maintenance period, but were impaired after a 7-s WM maintenance period and on the LTM task. Thus, parallel neuroimaging and lesion designs suggest that the same hippocampal processes support WM maintenance, for intervals as short as 7 s, and LTM for faces.
The medial temporal lobe (MTL)-hippocampus and surrounding perirhinal, parahippocampal, and entorhinal cortical areas-has long been known to be critical for long-term memory for events. Recent functional neuroimaging and neuropsychological data in humans performing short-delay tasks suggest that the MTL also contributes to performance even when retention intervals are brief, and singleunit data in rodents reveal sustained, performance-related delay activity in the MTL during delayed-non-match-to-sample tasks. The current study used functional magnetic resonance imaging to examine the relationship between activation in human MTL subregions and performance during a delayed-match-to-sample task with repeated (non-trial-unique) stimuli. On critical trials, the presentation of two faces was followed by a 30 s delay period, after which participants performed two-alternative forced-choice recognition. Functional magnetic resonance imaging revealed significant delay period activity in anterior hippocampus, entorhinal cortex, and perirhinal cortex over the 30 s retention interval, with the magnitude of activity being significantly higher on subsequently correct compared with subsequently incorrect trials. In contrast, posterior hippocampus, parahippocampal cortex, and fusiform gyrus activity linearly increased across the 30 s delay, suggesting an anticipatory response, and activity in parahippocampal cortex and hippocampus was greater during the probe period on correct compared with incorrect trials. These results indicate that at least two patterns of MTL delay period activation-sustained and anticipatory-are present during performance of short-delay recognition memory tasks, providing novel evidence that multiple processes govern task performance. Implications for understanding the role of the hippocampus and surrounding MTL cortical areas in recognition memory after short delays are discussed.
The selective loss of human chromosomes from both mouse + human and Chinese hamster x human somatic cell hybrids makes these two systems useful for studying problems in PGM has been linked to PEP C (54), which is on
The effects of the immunosuppressants cyclosporin A (CsA), FK506 and rapamycin have been compared using murine B cells activated with a variety of mitogens. FK506 is a macrolide antibiotic that has been recently shown to inhibit T cell activation by a mechanism that appears similar to that of CsA. Rapamycin is a macrolide structurally related to FK506 whose mechanism of T cell suppression appears to be distinct from that of FK506 and CsA. While CsA and FK506 were found to preferentially inhibit B cell activation caused by stimuli which induce a rise in intracellular calcium, rapamycin partially inhibited activation by all stimuli tested, including those which are not associated with a calcium flux. All three compounds were found to inhibit cell cycle progression within the G1 phase; however, the rapamycin-sensitive event within G1 was completed earlier than the G1 events inhibited by CsA and FK506. In addition, inhibition of anti-IgM-activated B cells with CsA and FK506, but not with rapamycin, resulted in cell death. These data suggest that although CsA, FK506 and rapamycin are all inhibitors of B cell activation, the inhibitory activity of rapamycin can be clearly distinguished from that of CsA and FK506. Although the suppressive effects of CsA and FK506 on B cell proliferation were nearly identical in this study, their biological activities were distinguishable since FK506, but not CsA, could antagonize rapamycin-mediated suppression.
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