Overexpression of type-1 adenylyl cyclase in mouse forebrain enhances recognition memory and LTP.
Cyclic AMP is a positive regulator of synaptic plasticity and is required for several forms of hippocampus-dependent memory including recognition memory. The type I adenylyl cyclase, Adcy1 (also known as AC1), is crucial in memory formation because it couples Ca(2+) to cyclic AMP increases in the hippocampus. Because Adcy1 is neurospecific, it is a potential pharmacological target for increasing cAMP specifically in the brain and for improving memory. We have generated transgenic mice that overexpress Adcy1 in the forebrain using the Camk2a (also known as alpha-CaMKII) promoter. These mice showed elevated long-term potentiation (LTP), increased memory for object recognition and slower rates of extinction for contextual memory. The increase in recognition memory and lower rates of contextual memory extinction may be due to enhanced extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling, which is elevated in mice that overexpress Adcy1.
Wang
Hongbing
H
Department of Pharmacology, University of Washington, Box 357280, 1959 NE Pacific Street, Seattle, Washington 98195-7280, USA.
Ferguson
Gregory D
GD
Pineda
Victor V
VV
Cundiff
Paige E
PE
Storm
Daniel R
DR
D000262:Adenylyl Cyclases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D017774:Long-Term Potentiation / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D016548:Prosencephalon / Q000378:metabolism*; D021641:Recognition, Psychology / Q000502:physiology*
C517657:CAMK2A protein, human; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1