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The Journal of Neuroscience, September 13, 2006, 26(37):9434-9438; doi:10.1523/JNEUROSCI.2538-06.2006

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Brief Communications
DARPP-32 Involvement in the Photic Pathway of the Circadian System

Lily Yan,¹ Jessica M. Bobula,¹ Per Svenningsson,² Paul Greengard,² and Rae Silver^1,3,4

¹Department of Psychology, Columbia University, New York, New York 10027, ²Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021, ³Department of Psychology, Barnard College, New York, New York 10027, and ⁴Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032

Correspondence should be addressed to Dr. Rae Silver, Department of Psychology, Columbia University, 1190 Amsterdam Avenue, New York, NY 10027. Email: qr{at}columbia.edu

The multifunctional regulator of protein kinases and phosphatases dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) is an important molecular target of the dopamine signaling pathway. In the present study, we investigated the possible involvement of DARPP-32 regulation in the circadian system using DARPP-32 knock-out (KO) mice. These mice showed normal entrainment to a 12 h light/dark cycle and free run in constant darkness with a period similar to that of wild-type controls. After light exposure, however, the behavioral phase-delay response and the expression of light-induced clock gene mPer2 were attenuated in the DARPP-32 KO mice. Attenuated phase delays were also seen in animals bearing a point mutation in DARPP-32 at the PKA (Thr34) but not at the casein kinase I (Ser130) phosphorylation site. We next examined DARPP-32 expression in the retina and intergeniculate leaflet (IGL), both of which convey light information to the suprachiasmatic nucleus (SCN), the locus of a master circadian clock, and in the SCN itself. DARPP-32 was expressed in the retina but not in the IGL or the SCN. The results indicate that DARPP-32 is involved in the retinal pathway transmitting photic information that resets the circadian clock.

Key words: DARPP-32; suprachiasmatic nucleus; phase shifts; circadian rhythm; photic transmission; retina

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Received June 16, 2006; revised Aug. 9, 2006; accepted Aug. 10, 2006.

Correspondence should be addressed to Dr. Rae Silver, Department of Psychology, Columbia University, 1190 Amsterdam Avenue, New York, NY 10027. Email: qr{at}columbia.edu

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