Type I adenylyl cyclase mutant mice have impaired mossy fiber long-term potentiation.
Long-term potentiation (LTP) at the mossy fiber-->CA3 pyramidal cell synapse in the hippocampus is an NMDA-independent form of LTP that requires cAMP-dependent protein kinase (PKA) activity and can be induced by forskolin, a general activator of adenylyl cyclases. Presynaptic Ca2+ influx and elevated cAMP may be obligatory for mossy fiber LTP. Because 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 examined several forms of hippocampal LTP in wild-type and AC1 mutant mice. Wild-type and AC1 mutant mice exhibited comparable perforant path LTP recorded in the dentate gyrus as well as decremental LTP at the Schaffer collateral-->CA1 pyramidal cell synapse. Although the mutant mice exhibited normal paired pulse facilitation, mossy fiber LTP was impaired significantly in AC1 mutants. High concentrations of forskolin induced mossy fiber LTP to comparable levels in wild-type and AC1 mutant mice, indicating that signaling components downstream from the adenylyl cyclase, including PKA, ion channels, and secretory machinery, were not affected by disruption of the AC1 gene. These data indicate that coupling of Ca2+ to activation of AC1 is crucial for mossy fiber LTP, most likely via activation of PKA and enhancement of excitatory amino acid secretion.
Villacres
E C
EC
Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.
Wong
S T
ST
Chavkin
C
C
Storm
D R
DR
D000262:Adenylyl Cyclases / Q000235:genetics*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D008818:Mice, Neurologic Mutants; D019599:Mossy Fibers, Hippocampal / Q000201:enzymology*; D019580:Perforant Pathway / Q000502:physiology
D005576:Colforsin; D000262:Adenylyl Cyclases; D002118:Calcium