Impaired long-term potentiation in vivo in the dentate... : NeuroReport (original) (raw)

MOLECULAR NEUROSCIENCE

Impaired long-term potentiation in vivo in the dentate gyrus of pituitary adenylate cyclase-activating polypeptide (PACAP) or PACAP type 1 receptor-mutant mice

Matsuyama, ShogoCA; Matsumoto, Akira1; Hashimoto, Hitoshi2; Shintani, Norihito2; Baba, Akemichi2 3

Division of Molecular Pharmacology and Pharmacogenomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017

1Brain Disease Pathogenesis Research Division, Foundation for Biomedical Research and Innovation, Kobe, 650-0047

2Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences

3Laboratory of Molecular Pharmacology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan

CACorresponding Author: [email protected]

Received 9 May 2003; accepted 11 June 2003

Abstract

The present study was conducted to clarify a role of pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP type 1 receptor (PAC1R) in learning and memory function. We demonstrated long-term potentiation (LTP) in vivo in the dentate gyrus of PAC1R exon 2-deficient (PAC1R−/−) mice and heterozygous PACAP-deficient (PACAP+/−) mice using extracellular recording techniques. We used two paradigms of tetanic stimulation, suprathreshold and at threshold tetanus, which both induced LTP in vivo in PAC1R−/− and PACAP+/− mice. However, the population spike of ‘at threshold’ but not ‘suprathreshold’ LTP decreased significantly in PAC1R−/− and PACAP+/− mice. At threshold LTP of PACAP+/− mice was impaired greater than the one of PAC1R−/− mice. Thus, both PACAP and PAC1R could contribute to the establishment of LTP in a gene dosage-dependent manner, although PACAP rather than PAC1R might play a pivotal role in learning and memory function.