Impaired long-term potentiation in vivo in the dentate gyrus of pituitary adenylate cyclase-activating polypeptide (PACAP) or PACAP type 1 receptor-mutant mice.
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.
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, Japan. shogo@med.kobe-u.ac.jp
Shogo
S
Matsuyama
Akira
A
Matsumoto
Hitoshi
H
Hashimoto
Norihito
N
Shintani
Akemichi
A
Baba
D000200:Action Potentials / Q000235:genetics; D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism* / Q000503:physiopathology; D004558:Electric Stimulation; D018628:Gene Dosage; D006579:Heterozygote; D006720:Homozygote; D007858:Learning / Q000502:physiology; D017774:Long-Term Potentiation / Q000235:genetics*; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009434:Neural Pathways / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D009479:Neuropeptides / Q000172:deficiency* / Q000235:genetics; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000172:deficiency* / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics
C495402:Adcyap1 protein, mouse; C495504:Adcyap1r1 protein, mouse; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone