Fig 1: Activation of D1/PKA rescues the decreased GluA1-containing AMPA receptor surface expression induced by ADDLs in cultured hippocampal neurons. (a–c) Surface expression of GluA1 (S-GluA1) and GluA2 (S-GluA2) were significantly decreased after treating with ADDLs (500 nM) for 3–24 h, whereas surface expression of GluA3 (S-GluA3) was not changed. Total expression of GluA1-3 (T-GluA) were not changed. (GluA1: n=5 in each group, GluA2: n=4 in each group, GluA3: n=4 in each group). (d) Phosphorylated levels of GluA1 at Serine 845 (pS845) and Serine 831 (pS831) were decreased after treating with ADDLs (pS845: n=9 in each group, pS831: n=9 in each group). (e) Pretreatment with PKA activator Sp-cAMPS (10 µM) rescued the decreased pS845 and surface expression of GluA1 induced by ADDLs, whereas the PKA inhibitor Rp-cAMPS (10 µM) reversed these effects. Sp-cAMPS or Rp-cAMPS was added 10 min before ADDLs (n=4 in each group). (f) Pretreatment with D1-type receptor agonist SKF 81297 (SKF, 3 µM) rescued the decreased pS845 and surface expression of GluA1 induced by ADDLs, whereas the antagonist SCH 23390 (SCH, 10 µM) reversed these effects. SKF 81297 or SCH 23390 was added 15 min before ADDLs (n=6 in each group). *P<0.05, **P<0.01, ***P<0.001 versus corresponding control group (Con); #P<0.05, ##P<0.01, ###P<0.001 versus corresponding ADDL group. Data are represented as mean±S.E.M