The mechanisms that determine how information is allocated to specific regions and cells in the brain are fundamentally important for memory capacity, storage and retrieval, but are poorly understood. Here, we manipulated CREB in a subset of lateral amygdala (LA) neurons with a modified Herpes Simplex Virus (HSV), and reversibly inactivated transfected neurons with the Drosophila allatostatin G-protein-coupled receptor (AlstR)/ligand system. We found that inactivation of the HSV-CREB subpopulation of neurons with allatostatin (AL) during training disrupted memory for tone conditioning, while inactivation of a similar proportion of HSV-LacZ control neurons did not. Whole-cell recordings of fluorescently tagged HSV-CREB neurons revealed that neurons with higher CREB levels are more excitable than neighboring neurons, and show larger synaptic efficacy changes following conditioning. Our findings demonstrate that CREB modulates the allocation of fear memory to specific cells in lateral amygdala, and suggest that neuronal excitability plays a key role in this process.

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Aberrant activation of Wnt/␤-catenin signaling and subsequent up-regulation of ␤-catenin response transcription (CRT) is a critical event in the development of human colon cancer. Thus, Wnt/␤-catenin signaling is an attractive target for the development of anticancer therapeutics. In this study, we identified hexachlorophene as an inhibitor of Wnt/␤-catenin signaling from cell-based small-molecule screening. Hexachlorophene antagonized CRT that was stimulated by Wnt3a-conditioned medium by promoting the degradation of ␤-catenin. This degradation pathway is Siah-1 and adenomatous polyposis colidependent, but glycogen synthase kinase-3␤ and F-box ␤-transducin repeat-containing protein-independent. In addition, hexachlorophene represses the expression of cyclin D1, which is a known ␤-catenin target gene, and inhibits the growth of colon cancer cells. Our findings suggest that hexachlorophene attenuates Wnt/␤-catenin signaling through the Siah-1-mediated ␤-catenin degradation.

when seasonality is accounted for, reasonable local temperature estimates can be drawn from the GRIP isotopic record; the correction due to source temperature changes is of lesser importance at glacial-interglacial scales than during rapid events. Moreover, the comparison between our estimate of DT source and available North Atlantic sediment-based SST reconstructions suggests that large changes in geographical moisture source location occur both at the orbital and millennial scales. We show that DT source reflects obliquity changes and that DT source and DT site are of opposite sign, both at orbital and millennial time scales. The influence of obliquity on deuterium excess and moisture origin, already identified for Antarctica, is confirmed for Greenland. When cold conditions prevail in the mid-and high latitudes, the moisture origin shifts to milder southward locations (5). Finally, we point to striking similarities between the calcium-dust records and the site-to-source temperature gradient; both are strongly modulated by obliquity, and the coupled climate model results suggest that obliquity could be linked with dust source areas through the land-sea temperature contrast. At the millennial time scale, the site-to-source temperature fluctuations highlight large-scale changes in atmospheric circulation, which is consistent with the observation of simultaneous rapid climate changes at polar, temperate, and tropical latitudes (40) also recorded in Greenland ice chemistry and methane fluctuations (41). Modeling studies have indeed shown that Northern Hemisphere storm tracks are influenced not only by the topography of the ice sheets but also by the sea-ice extent and the meridional temperature gradients (30).Such large changes in the atmospheric hydrological cycle and associated climate feedbacks are not fully represented in the intermediatecomplexity climate models commonly used to understand the mechanisms of abrupt events. Nonetheless, they could play a key role in the generation of instabilities of the ice sheets and the ocean circulation, amplified by changes in sea-ice extent, as has been suggested for the last glacial inception (42).