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Because both growth factor signaling and glucose have been implicated in memory formation, we questioned whether mTOR activity is required for long-term spatial memory formation and whether this cascade is involved in the memory-augmenting effect of centrally applied glucose. To test our hypothesis, we directly administered rapamycin (an inhibitor of mTOR), glucose, 5-aminoimidazole-4-carboxamide-1\u03b2-4-ribonucleoside (AICAR; an activator of AMP kinase), or glucose plus rapamycin into the dorsal hippocampus after we trained rats in the Morris water maze task. The results from these studies indicate that glucose enhances, whereas AICAR and rapamycin both impair, long-term spatial memory. Furthermore, the memory-impairing effect of targeted rapamycin administration could not be overcome by coadministration of glucose. Consistent with these behavioral results, biochemical analysis revealed that glucose and AICAR had opposing influences on the activation of the TSC\u2013mTOR cascade, as indicated by the phosphorylation of ribosomal S6 kinase (S6K) and 4E binding protein 1 (4EBP1), targets of mTOR. Together, these findings suggest that memory formation requires the mTOR cascade and that the memory-enhancing effect of glucose involves its ability to activate this pathway.<\/jats:p>","DOI":"10.1523\/jneurosci.0671-06.2006","type":"journal-article","created":{"date-parts":[[2006,8,2]],"date-time":"2006-08-02T23:47:05Z","timestamp":1154562425000},"page":"8048-8056","source":"Crossref","is-referenced-by-count":141,"title":["Spatial Memory Formation and Memory-Enhancing Effect of Glucose Involves Activation of the Tuberous Sclerosis Complex\u2013Mammalian Target of Rapamycin Pathway"],"prefix":"10.1523","volume":"26","author":[{"given":"Pramod K.","family":"Dash","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara A.","family":"Orsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony N.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2006,8,2]]},"reference":[{"key":"2023041303194856000_26.31.8048.1","doi-asserted-by":"publisher","DOI":"10.1038\/2836"},{"key":"2023041303194856000_26.31.8048.2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02244373"},{"key":"2023041303194856000_26.31.8048.3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.55.030193.002145"},{"key":"2023041303194856000_26.31.8048.4","doi-asserted-by":"publisher","DOI":"10.1038\/45287"},{"key":"2023041303194856000_26.31.8048.5","doi-asserted-by":"crossref","first-page":"10037","DOI":"10.1523\/JNEUROSCI.18-23-10037.1998","volume":"18","year":"(1998)","journal-title":"J Neurosci"},{"key":"2023041303194856000_26.31.8048.6","doi-asserted-by":"publisher","DOI":"10.1101\/lm.74104"},{"key":"2023041303194856000_26.31.8048.7","doi-asserted-by":"crossref","first-page":"3535","DOI":"10.1523\/JNEUROSCI.19-09-03535.1999","volume":"19","year":"(1999)","journal-title":"J Neurosci"},{"key":"2023041303194856000_26.31.8048.8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200171200"},{"key":"2023041303194856000_26.31.8048.9","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.047019"},{"key":"2023041303194856000_26.31.8048.10","doi-asserted-by":"publisher","DOI":"10.1101\/lm.88205"},{"key":"2023041303194856000_26.31.8048.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81653-0"},{"key":"2023041303194856000_26.31.8048.12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1995.tb20498.x"},{"key":"2023041303194856000_26.31.8048.13","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20078"},{"key":"2023041303194856000_26.31.8048.14","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20174"},{"key":"2023041303194856000_26.31.8048.15","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1994.11.275"},{"key":"2023041303194856000_26.31.8048.16","doi-asserted-by":"publisher","DOI":"10.1038\/385533a0"},{"key":"2023041303194856000_26.31.8048.17","doi-asserted-by":"publisher","DOI":"10.1038\/ncb847"},{"key":"2023041303194856000_26.31.8048.18","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-1047(86)80022-X"},{"key":"2023041303194856000_26.31.8048.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.13.4549"},{"key":"2023041303194856000_26.31.8048.20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.6.2693"},{"key":"2023041303194856000_26.31.8048.21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.26.14866"},{"key":"2023041303194856000_26.31.8048.22","doi-asserted-by":"publisher","DOI":"10.1126\/science.1715094"},{"key":"2023041303194856000_26.31.8048.23","doi-asserted-by":"publisher","DOI":"10.1038\/ncb839"},{"key":"2023041303194856000_26.31.8048.24","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00929-2"},{"key":"2023041303194856000_26.31.8048.25","doi-asserted-by":"publisher","DOI":"10.1038\/ng1494"},{"key":"2023041303194856000_26.31.8048.26","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.69.1.79-100.2005"},{"key":"2023041303194856000_26.31.8048.27","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2270-05.2005"},{"key":"2023041303194856000_26.31.8048.28","doi-asserted-by":"crossref","unstructured":"Jefferies HB, Fumagalli S, Dennis PB, Reinhard C, Pearson RB, Thomas G (1997) Rapamycin suppresses 5\u2032-TOP mRNA translation through inhibition of p70s6k. 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