Calcium-stimulated adenylyl cyclase activity is critical for hippocampus-dependent long-term memory and late phase LTP.
It is hypothesized that Ca2+ stimulation of calmodulin (CaM)-activated adenylyl cyclases (AC1 or AC8) generates cAMP signals critical for late phase LTP (L-LTP) and long-term memory (LTM). However, mice lacking either AC1 or AC8 exhibit normal L-LTP and LTM. Here, we report that mice lacking both enzymes (DKO) do not exhibit L-LTP or LTM. To determine if these defects are due to a loss of cAMP increases in the hippocampus, DKO mice were unilaterally cannulated to deliver forskolin. Administration of forskolin to area CA1 before training restored normal LTM. We conclude that Ca2+-stimulated adenylyl cyclase activity is essential for L-LTP and LTM and that AC1 or AC8 can produce the necessary cAMP signal.
Wong
S T
ST
Department of Pharmacology, University of Washington School of Medicine, Seattle 98195, USA.
Athos
J
J
Figueroa
X A
XA
Pineda
V V
VV
Schaefer
M L
ML
Chavkin
C C
CC
Muglia
L J
LJ
Storm
D R
DR
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D003463:Cues; D004594:Electrophysiology; D005239:Fear / Q000502:physiology / Q000523:psychology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D007150:Immunohistochemistry; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal
D002147:Calmodulin; D005576:Colforsin; D000262:Adenylyl Cyclases; D002118:Calcium