Differential activation of adenylyl cyclases by spatial and procedural learning

Adenylyl cyclases (ACs) are involved in a variety of advanced CNS functions, including some types of learning and memory. At least nine AC isoforms are expressed in the brain, which are divisible into three broad classes based on the ability of Ca2+ to modulate their activity. This study examined the hypothesis that different learning tasks would differentially activate ACs in selected brain regions. The ability of forskolin or Ca2+ to enhance AC activity in the hippocampus, parietal cortex, striatum, and cerebellum was examined after mice had been trained in either a spatial or procedural learning task using a Morris water maze. Sensitivity of ACs to forskolin was enhanced to a greater degree in most brain regions after procedural learning, but Ca2+-sensitive ACs in the hippocampus were more sensitive to spatial learning. Because nonspecific behavioral elements, such as stress or motor activity, were similar in both experimental tasks, these results provide the first evidence that acquisition of different kinds of learning is associated with selective changes in particular AC species in a mammalian brain and support the idea that different biochemical processing, involving particular isoforms of ACs, subserves different memory systems.