Spatial learning induces differential changes in calcium/calmodulin-stimulated (ACI) and calcium-insensitive (ACII) adenylyl cyclases in the mouse hippocampus

Several lines of evidence indicate that Ca2+/calmodulin-stimulated isoforms of adenylyl cyclase (AC) are involved in long-term potentiation and in certain forms of learning. Recently, we found that training in different types of learning task differentially activates Ca2+-sensitive versus Ca2+-insensitive AC activities in certain brain regions, indicating that AC species other than those stimulated by Ca2+/calmodulin may play an important role in learning processes (Guillou, Rose, & Cooper, 1999). Here, we report the effects of spatial reference memory training in a radial arm maze on the levels of AC1 and AC2 mRNA in the dorsal hippocampus of C57BL/6 mice. Acquisition of the task was associated with a learning-specific and time-dependent increase of AC1 mRNA expression selectively in subfields CA1-CA2. In contrast, AC2 mRNA levels were either reduced or not reliably affected depending on the stage of acquisition. Moreover, no significant changes in AC expression were observed either in the dorsal hippocampus of mice trained in a non-spatial (procedural) version of the task or in cortical regions of mice learning the spatial or procedural task. The regional specificity of these effects indicates that the formation of spatial and non-spatial memory requires distinct contributions from Ca2+-sensitive and Ca2+-insensitive AC in the hippocampus. It is suggested that downregulation of AC2 throughout all hippocampal subfields may play a permissive role during the acquisition of spatial learning whereas an upregulation of AC1 specifically in subfield CA1, may be critical to accurately encode, store or use spatial information.