TYPE-I ADENYLYL-CYCLASE MUTANT MICE HAVE IMPAIRED MOSSY FIBER LONG-TERM POTENTIATION

Citation
Ec. Villacres et al., TYPE-I ADENYLYL-CYCLASE MUTANT MICE HAVE IMPAIRED MOSSY FIBER LONG-TERM POTENTIATION, The Journal of neuroscience, 18(9), 1998, pp. 3186-3194
Citations number
68
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
0270-6474
Volume
18
Issue
9
Year of publication
1998
Pages
3186 - 3194
Database
ISI
SICI code
0270-6474(1998)18:9<3186:TAMMHI>2.0.ZU;2-G
Abstract
Long-term potentiation (LTP) at the mossy fiber-->CA3 pyramidal cell s ynapse in the hippocampus is an NMDA-independent form of LTP that requ ires cAMP-dependent protein kinase (PKA) activity and can be induced b y forskolin, a general activator of adenylyl cyclases. Presynaptic Ca2 + influx and elevated cAMP may be obligatory for mossy fiber LTP. Beca use the Ca2+-stimulated type 1 adenylyl cyclase (AC1) is expressed in the dentate gyrus and CA3 pyramidal cells, it is hypothesized that AC1 may be critical for mossy fiber LTP. To test this hypothesis, we exam ined several forms of hippocampal LTP in wild-type and AC1 mutant mice . Wild-type and AC1 mutant mice exhibited comparable perforant path LT P recorded in the dentate gyrus as well as decremental LTP at the Scha ffer collateral-->CA1 pyramidal cell synapse. Although the mutant mice exhibited normal paired pulse facilitation, mossy fiber LTP was impai red significantly in AC1 mutants. High concentrations of forskolin ind uced messy fiber LTP to comparable levels in wild-type and AC1 mutant mice, indicating that signaling components downstream from the adenyly l cyclase, including PKA, ion channels, and secretory machinery, were not affected by disruption of the AC1 gene. These data indicate that c oupling of Ca2+ to activation of AC1 is crucial for messy fiber LTP, m ost likely via activation of PKA and enhancement of excitatory amino a cid secretion.