Ca-stimulated type 8 adenylyl cyclase is required for rapid acquisition of novel spatial information and for working/episodic-like memory.
Ca-stimulated adenylyl cyclases (ACs) transduce neuronal stimulation-evoked increase in calcium to the production of cAMP, which impinges on the regulation of many aspects of neuronal function. Type 1 and type 8 AC (AC1 and AC8) are the only ACs that are directly stimulated by Ca. Although AC1 function was implicated in regulating reference spatial memory, the function of AC8 in memory formation is not known. Because of the different biochemical properties of AC1 and AC8, these two enzymes may have distinct functions. For example, AC1 activity is regulated by both Ca and G-proteins. In contrast, AC8 is a pure Ca sensor. It is neither stimulated by G(s) nor inhibited by G(i). Recent studies also suggested that AC1 and AC8 were differentially concentrated at different subcellular domains, implicating that Ca-stimulated signaling might be compartmentalized. In this study, we used AC8 knock-out (KO) mice and found behavioral deficits in memory retention for temporal dissociative passive avoidance and object recognition memory. When examined by Morris water maze, AC8 KO mice showed normal reference memory. However, the acquisition of newer spatial information was defective in AC8 KO mice. Furthermore, AC8 KO mice were severely impaired in hippocampus-dependent episodic-like memory when examined by the delayed matching-to-place task. Because AC8 is preferentially localized at the presynaptic active zone, our results suggest a novel role of presynaptic cAMP signaling in memory acquisition and retention, as well as distinct mechanisms underlying reference and working/episodic-like memory.
Zhang
Ming
M
Department of Physiology, Michigan State University, East Lansing, Michigan 48824, USA.
Moon
Changjong
C
Chan
Guy C-K
GC
Yang
Lan
L
Zheng
Fei
F
Conti
Alana C
AC
Muglia
Lisa
L
Muglia
Louis J
LJ
Storm
Daniel R
DR
Wang
Hongbing
H
D000262:Adenylyl Cyclases / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology*; D006624:Hippocampus / Q000293:injuries / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021641:Recognition, Psychology / Q000502:physiology*; D013037:Spatial Behavior / Q000502:physiology*
D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1; C118292:adenylyl cyclase 8