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D.d.G., unpublished data; Shin et?al., 2012). It is possible that our nonassociative habituation assay lacks the necessary sensitivity to detect relatively subtle learning OTX015 clinical trial deficiencies in larvae with these genotypes. Attenuating Ras signaling by acute pharmacological inhibition of MAPK (U0126) or PI3K (wortmannin) failed to improve the learning deficit of nf1a?/?; nf1b?/? larvae ( Figures 2B and S1B), suggesting that a distinct pathway mediates NF1-dependent learning. Whole larval lysates revealed reduced cAMP levels in nf1a?/?; nf1b?/? mutants compared with wild-type controls (nf1a?/?; nf1b?/?: 33 fmol �� SEM 2.3 versus wild-type: 79 fmol �� SEM 7.8, p?Transducin and nf1a+/?; nf1b?/? larvae, which learn normally but fail to form memory, and compared them with wild-type controls. Treatment with 10?��M 8-Br-cAMP, a sufficient dose to restore learning in nf1a?/?; nf1b?/? larvae ( Figures 2E and S1D), failed to improve memory recall in either nf1a+/?; nf1b?/? or nf1a?/?; nf1b?/? larvae ( Figure?S2). These results suggest that cAMP signaling regulates NF1-dependent learning but not BTK inhibitor memory. Moreover, these results indicate that the memory defects in nf1a?/?; nf1b?/? mutants are not simply attributable to their learning deficit. These data strongly imply that molecularly distinct pathways that control learning and memory are affected in NF1. Learned behavior requires consolidation to form stable memory. Despite consensus that defective neurofibromin function can result in learning and memory impairments, whether impaired consolidation contributes to memory deficits remains unclear. nf1a+/?; nf1b?/? larvae learn normally (M.A.W. and E.D.d.G., unpublished data; Shin et?al., 2012) but show reduced memory recall ( Figure?1C). Therefore, we asked whether reduced memory was due to a consolidation deficit. We determined memory consolidation by calculating the difference between the mean O-bend latency in response to the first five dark-flash stimuli of training session 1 and subsequent training sessions ( Figure?3A).