title: Learning defects in Drosophila growth restricted chico mutants are caused by attenuated adenylyl cyclase activity.
abstract: BACKGROUND
  Reduced insulin/insulin-like growth factor signaling (IIS) is a major cause of symmetrical intrauterine growth retardation (IUGR), an impairment in cell proliferation during prenatal development that results in global growth defects and mental retardation. In Drosophila, chico encodes the only insulin receptor substrate. Similar to other animal models of IUGR, chico mutants have defects in global growth and associative learning. However, the physiological and molecular bases of learning defects caused by chico mutations, and by symmetrical IUGR, are not clear.
  
  
  RESULTS
  In this study, we found that chico mutations impair memory-associated synaptic plasticity in the mushroom bodies (MBs), neural centers for olfactory learning. Mutations in chico reduce expression of the rutabaga-type adenylyl cyclase (rut), leading to decreased cAMP synthesis in the MBs. Expressing a rut (+) transgene in the MBs restores memory-associated plasticity and olfactory associative learning in chico mutants, without affecting growth. Thus chico mutations disrupt olfactory learning, at least in part, by reducing cAMP signaling in the MBs.
  
  
  CONCLUSIONS
  Our results suggest that some cognitive defects associated with reduced IIS may occur, independently of developmental defects, from acute reductions in cAMP signaling.
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya, 185-8506, Tokyo, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Naganos
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya, 185-8506, Tokyo, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Ueno
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya, 185-8506, Tokyo, Japan.
authors.forename: Junjiro
authors.initials: J
authors.lastname: Horiuchi
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya, 185-8506, Tokyo, Japan. saito-mn@igakuken.or.jp.
authors.forename: Minoru
authors.initials: M
authors.lastname: Saitoe
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002452:Cell Count; D000242:Cyclic AMP / Q000096:biosynthesis; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000254:growth & development* / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics* / Q000378:metabolism; D007858:Learning; D024521:Mushroom Bodies / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D019076:Transgenes
chemical_list: D029721:Drosophila Proteins; D055504:Insulin Receptor Substrate Proteins; C120233:chico protein, Drosophila; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C479926:Rut protein, Drosophila
keywords: Associative learning; Insulin signaling; Intrauterine growth retardation; Synaptic plasticity; cAMP