The Mouse Circadian Clock In Vitro: A Role For The Map Kinase Signalling Pathway

Biello, S.M. (2000) The Mouse Circadian Clock In Vitro: A Role For The Map Kinase Signalling Pathway. Society for Neuroscience Abstract, 76(42),

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The suprachiasmatic nuclei (SCN) contain a circadian clock whose activity can be recorded in vitro for several days. Photic information is conveyed to the SCN via a direct projection from the retina, utilizing an excitatory amino acid neurotransmitter. Photic phase shifts may be mimicked by application of glutamate to the SCN in vitro. Here we examine the role of the MAP kinase signaling pathway in the phase-resetting effects of glutamate. Hypothalamic slices containing the SCN were obtained during the light phase from adult male Balb/c mice and continuously perfused with oxygenated ACSF in a brain slice chamber. Extracellular recordings were made from spontaneously discharging neurones from 24h to 72h following slice preparation. Circadian variation in the electrical activity in untreated, control slices peaked at the middle of the projected light phase [zeitgeber time (ZT)6-7, n=11, mean peak (mp)=6.3, SEM=0.2,where ZT0=projected lights on] on days two and three following slice preparation. Microdrop applications of glutamate (10-3M, 200nl) early in the projected night (ZT15), delayed the peak in this rhythm (n=7, mp=10.1, SEM=0.2) while those late in the projected night (ZT22.5) advanced the peak (n=7, mp=4.0, SEM=0.2). Glutamate application during the middle portion of the projected day did not alter the peak in this rhythm. Pretreatment with a specific MEK inhibitor P98059 attenuated both delays (n=5, mp=8.7, SEM=0.3) and advances to glutamate (n=6, mp=5.1, SEM=0.2). P98059 did not phase shift the peak electrical activity rhythm when applied alone during the projected night (ZT15 or 22.5). These results indicate that the MAPK pathway may be involved in phase shifts to photic stimuli in the mouse.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Biello, Professor Stephany
Authors: Biello, S.M.
College/School:College of Science and Engineering > School of Psychology
Journal Name:Society for Neuroscience Abstract

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