Matsuyama Shogo, Matsumoto Akira, Hashimoto Hitoshi, Shintani Norihito, Baba Akemichi
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.
Neuroreport. 2003 Nov 14;14(16):2095-8. doi: 10.1097/00001756-200311140-00017.
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.
本研究旨在阐明垂体腺苷酸环化酶激活多肽（PACAP）和PACAP 1型受体（PAC1R）在学习和记忆功能中的作用。我们使用细胞外记录技术，在PAC1R外显子2缺陷（PAC1R-/-）小鼠和杂合PACAP缺陷（PACAP+/-）小鼠的齿状回中证明了体内长时程增强（LTP）。我们使用了两种强直刺激范式，即阈上强直刺激和阈下强直刺激，二者均能在PAC1R-/-和PACAP+/-小鼠体内诱导LTP。然而，在PAC1R-/-和PACAP+/-小鼠中，“阈下”而非“阈上”LTP的群体峰电位显著降低。PACAP+/-小鼠的阈下LTP受损程度大于PAC1R-/-小鼠。因此，尽管PACAP而非PAC1R可能在学习和记忆功能中起关键作用，但PACAP和PAC1R均可通过基因剂量依赖性方式促进LTP的建立。
