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U Frey

Publications and source records attributed to U Frey.

96 records · Page 6Linked to original sources
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Weak before strong: dissociating synaptic tagging and plasticity-factor accounts of late-LTP.

Experiments were conducted using hippocampal slices in vitro to compare two accounts of the mechanisms by which input-specific protein synthesis-dependent long-term potentiation (late-LTP) may be realised. The synaptic tag hypothesis (Frey and Morris, 1997) predicts that the expression of early-LTP following a weak tetanus can be stabilised into late-LTP by subsequent strong tetanisation of a separate pathway, provided the interval between the two tetanisation episodes is within the decay time-course of a putative synaptic tag. An alternative plasticity-factors hypothesis requires that strong tetanisation should always precede weak tetanisation for stabilisation of early-LTP to occur. Our results indicate that weak tetanisation of pathway S2 at intervals of 5 min or 1 h prior to strong tetanisation on pathway S1 does result in late-LTP on pathway S2. Stabilisation was weaker or did not occur at intervals of 2 and 4 h. This stabilisation effect was shown to depend on protein synthesis during the strong tetanisation of S1. These findings uphold a key prediction of the synaptic tag hypothesis and have implications for the functional role of synaptic tagging for cortical plasticity.

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Deficits in memory tasks of mice with CREB mutations depend on gene dosage.

Studies in Aplysia, Drosophila, and mice have shown that the transcription factor CREB is involved in formation and retention of long-term memory. To analyze the impact of differential CREB levels on learning and memory, we varied the gene dosage of CREB in two strains of mutant mice: (1) CREBalphadelta mice, in which the alpha and delta isoforms are disrupted, but a third isoform beta is strongly up-regulated; (2) CREBcomp, a compound strain with one alphadelta allele and one CREBnull allele in which all CREB isoforms are disrupted. To minimize genetic background effects, CREB mutations were backcrossed into a C57BL/6 and a FVB/N strain, respectively, and studies were performed in F1 hybrids from these lines. CREBcomp but not CREBalphadelta F1 hybrids were impaired in water maze learning and fear conditioning, demonstrating a CREB gene dosage effect. However, analysis of the platform searching strategies in the water maze task suggested that CREBcomp mutants are impaired in behavioral flexibility rather than in spatial memory. In contrast to previous experiments using CREBalphadelta mice with different genetic background, the F1 hybrid CREBalphadelta and CREBcomp mice did not show deficits in a social transmission of food preference task nor in dentate gyrus and CA1 LTP as recorded from slice preparations. These data indicate that the hybrid vigor typical for F1 hybrids may compensate for a reduction in CREB levels in some tests. On the other hand, the persistence of clear behavioral deficits as shown by the F1 hybrid CREBcomp mice in water maze and fear conditioning indicates a robust and repeatable phenomenon that will permit further functional analysis of CREB.

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