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 ar e expressed in the brain, which are divisible into three broad classes base d on the ability of Ca2+ to modulate their activity. This study examined th e hypothesis that different learning tasks would differentially activate AC s 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 lea rning task using a Morris water maze. Sensitivity of ACs to forskolin was e nhanced 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 th e first evidence that acquisition of different kinds of learning is associa ted with selective changes in particular AC species in a mammalian brain an d support the idea that different biochemical processing, involving particu lar isoforms of ACs, subserves different memory systems.