Differential regulation of Ca2+-calmodulin stimulated and Ca2+-insensitiveadenylyl cyclase messenger RNA in intact and denervated mouse hippocampus

The Ca2+-calmodulin stimulated AC1 and Ca2+-insensitive AO, are major isofo rms of adenylyl cyclase, playing an important role in synaptic plasticity i n the mammalian brain. We studied the pattern of expression of AC1 and AC2 genes in the hippocampus of C57BL/6 mice. We found that there were differen ces in their patterns of distribution in the dentate gyrus. AC1 messenger R NA was detected both in the dentate granule cell bodies and the correspondi ng molecular field whereas AC2 messenger RNA was preferentially distributed in the dentate granule cell layer, suggesting that AC1 and AC2 messenger R NA are differentially regulated in the dentate gyrus. In order to examine t he regulation of ACI and AU expression in response to synaptic deafferentat ion and reinnervation, the distribution patterns of the two AC messenger RN A in the hippocampal fields and the parietal cortex were analysed 2, 5, 9 a nd 30 days following an unilateral entorhinal cortex lesion. Interestingly, we found significantly reduced levels of AC1 hybridization signal followin g the lesion whereas the level of AC2 messenger RNA remained unaffected in all lesioned groups. The changes in ACI messenger RNA were transient, with a maximal reduction at five days postlesion, and were restricted to the gra nule cell bodies and stratum moleculare of the deafferented dentate gyrus. No significant change in ACI messenger RNA levels was detected in other hip pocampal fields nor for any other postlesion times studied. These findings suggest that, at least in the dentate gyrus, messenger RNA f or AC1 and AC2 might be differentially compartmentalized in cell bodies and dendritic fields. The activity-dependent regulation of AC1 messenger RNA l evels by afferent synapses may provide an elegant mechanism for achieving a selective local regulation of AC1 protein, close to its site of action. (C ) 2000 IBRO. Published by Elsevier Science Ltd.