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The Journal of Neuroscience, January 15, 2003, 23(2):652-658

Intrinsic Role of Polysialylated Neural Cell Adhesion Molecule in Photic Phase Resetting of the Mammalian Circadian Clock

Rebecca A. Prosser¹, Urs Rutishauser², Grace Ungers², Lenka Fedorkova³, and J. David Glass³

¹ Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee 37996, ² Program in Cellular Biochemistry and Biophysics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, and ³ Department of Biological Sciences, Kent State University, Kent, Ohio 44242

The suprachiasmatic nuclei (SCN), the location of the mammalian circadian clock, are one of the few adult brain regions that express the highly polysialylated form of neural cell adhesion molecule (PSA-NCAM). A role for the polysialic acid (PSA) component of PSA-NCAM, which is known to promote tissue plasticity, has been reported for photic entrainment of circadian rhythmicity in vivo. The in vivo results, however, do not discriminate between PSA acting upstream or downstream of the glutamatergic synapses that convey photic information to the SCN. To address this key issue, we exploited an in vitro rat brain slice preparation that retains robust circadian function. As in the intact SCN, PSA levels in the isolated SCN are rhythmic, with higher levels during the early subjective day and lower levels during subjective night. Importantly, bath application of glutamate to SCN slices rapidly and transiently increases PSA levels during both the subjective day and night. Pretreating the slices with endoneuraminidase, which selectively removes PSA from NCAM and thereby prevents this increase, abolishes glutamate- and optic chiasm stimulation-induced phase delays of the SCN circadian neuronal activity rhythm. These results support the hypothesis that PSA expression in the SCN is controlled by both the circadian clock and photic input to the clock and that expression of PSA in the SCN is critical for photic-like phase shifts of the clock. Together, these results establish that such actions of PSA are manifested downstream from presynaptic retinohypothalamic terminals and therefore are intrinsic to the SCN itself.

Key words: circadian rhythms; suprachiasmatic nucleus; polysialic acid; NCAM; phase-shift; glutamate; endoneuraminidase

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Copyright © 2003 Society for Neuroscience  0270-6474/03/232652-07$05.00/0

This article has been cited by other articles:

				A. Dityatev, G. Dityateva, V. Sytnyk, M. Delling, N. Toni, I. Nikonenko, D. Muller, and M. Schachner Polysialylated Neural Cell Adhesion Molecule Promotes Remodeling and Formation of Hippocampal Synapses J. Neurosci., October 20, 2004; 24(42): 9372 - 9382. [Abstract] [Full Text] [PDF]

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