"we used reporter transgenic worms in which GFP expression is controlled by the CRE reporter (pCRE::GFP) (Kimura et al., 2002). In untrained worms, CREB activity is barely detectible (Figure 4A). After spaced butanone/food long-term memory training, we observed fluorescence in two sets of neurons (Figures 4A and 4B)... To examine the dynamics of CREB activation, we quantified the levels of pCRE::GFP fluorescence in populations of LTAM-trained worms. While phosphorylated CREB levels rise fairly linearly with training, pCRE::GFP fluorescence increased markedly after 3-4 training sessions, paralleling the increase in LTAM performance (Figures 5A and 5D). Mutants of
unc-43 and
jnk-1, both activators of CREB (Johannessen et al., 2004) and downstream targets of CREB (Table S5), blocked the pCRE::GFP fluorescence increase (Figures 5B-5D), suggesting that a feedforward mechanism of CREB activation of its own upstream activators occurs with every food/butanone training cycle."