Analysis of brain functions of PACAP using its specific receptor PAC1 transgenic mice.

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To define the physiological roles of pituitary adenylate cyclase-activating polypeptide (PACAP), we developed the PACAP-preferring receptor (PAC1) transgenic (Tg) mice using the Cre/loxP recombination system. The three type of PAC1 Tg mice which were expressed the Pac1 transgene in the whole body (wPAC1 Tg mice), in the hippocampus (hPAC1 Tg mice), and in the hippocampus after tamoxifen treatment (ihPAC1 Tg mice), were obtained.We studied here the physiological roles of PACAP in brain using these PAC1 Tg mice. The spontaneous motor activity in home cage, the PAC1 expression, especially in hippocampus, increased behavioral activity at early dark period (ZT 12-17) which is most active time zone of the wild type mice. Furthermore, on the aged-mice which generally depressed motor activity, hPAC1 Tg mice showed more active with a clockwork circadian rhythm. These results suggest that the expression of PAC1 transgene, especially in the hippocampus nerve cells, make to enhance the behavioral activity with regular circadian rhythm. On the other hand, we studied the effect of PACAP in developmental respiratory adaptation by whole-body plethysmography and ex vivo analysis using brainstem-spinal cord preparation. Although this study is primitive, up to now, it was suggested that PACAP signaling concerned the development of central respiratory rhythmgensis.